ES2360254T3 - SUITABLE ARYLOXYETHYLAMINE COMPOUNDS FOR TREATMENT OF DISORDERS THAT RESPOND TO THE MODULATION OF DOPAMINE D3 RECEIVER. - Google Patents

Abstract

An aryloxyethylamine compound of the formula 1 ** Formula ** where Ar is phenyl or an aromatic radical of 5 or 6 heteroaromatic members linked by C, where Ar can carry a radical Ra and where Ar can also carry 1 or 2 radicals Rb; Ra is selected from the group consisting of C1-C6 alkyl, fluorinated C1-C6 alkyl, C2-C6 alkenyl, C2-C6 fluorinated alkenyl, C3-C6 cycloalkyl, fluorinated C3-C6 cycloalkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy , C1-C6 hydroxyalkyl, C1-C4 alkyl-C1-C6 alkoxy, C1-C6 hydroxyalkoxy, C1-C4 alkoxy-C1-C6 alkoxy, COOH, NR4R5, CH2NR4R5, ONR4R5, NHC (O) NR4R5, C (O) NR4R5 , SO2NR4R5, C1-C6 alkylcarbonyl, fluorinated C1-C6 alkylcarbonyl, C1-C6 alkylcarbonylamino, C1-C6 alkyl amino fluorinated amino, C1-C6 alkylcarbonyloxy, C1-C6 alkyl fluorinated carbonyloxy, C1-C6 alkoxycarbonyl, C1-fluorinated C6- alkoxycarbonyl, C1-C6 alkylthio, fluorinated C1-C6 alkylthio, C1-C6-alkylsulfinyl, C1-C6 alkyl fluorinated sulfinyl, C1-C6 alkyl sulfonyl, C1-C6 fluorinated alkyl sulfonyl, phenylsulfonyl, phenyl, phenoxy, benzyloxy, pyridine -2- yloxy and a 3- to 7-membered heterocyclic radical, where the phenyl groups, the pyridyl group and the heterocyclyl group in the last six radicals mentioned p They may carry 1, 2, 3 or 4 radicals selected from halogen, cyano, OH, oxo, CN, and a Raa radical, where Raa is selected from C1-C6 alkyl, fluorinated C1-C6 alkyl, C2-C6 alkenyl, fluorinated alkenyl C2-C6, C3-C6 cycloalkyl, fluorinated C3-C6 cycloalkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy, Hydroxyalkyl C1-C6, Alkoxy C1-C6-C1-C4-alkyl, Hydroxyalkoxy C1-C6, Alkoxy C1- C4-C1-C6 alkoxy, COOH, NR4R5, CH2NR4R5, ONR4R5, NHC (O) NR4R5, C (O) NR4R520, SO2NR4R5, C1-C6 alkylcarbonyl, C1-C6 alkyl fluorinated carbonyl, C1-C6 alkylcarbonylamino, C1- alkyl C6 fluorinated amino carbonyl, C1-C6 alkylcarbonyloxy, C1-C6 alkyl fluorinated carbonyloxy, C1-C6 alkoxycarbonyl, C1-C6 fluorinated alkoxycarbonyl, C1-C6 alkyl, fluorinated C1-C6 alkyl, C1-C6 alkyl sulfinyl, C1 alkyl -C6 fluorinated sulfinyl, C1-C6 alkyl sulfonyl, C1-C6 alkyl fluorinated sulfonyl, each Rb is selected from halogen, cyano, nitro, OH, methyl, methoxy, fluoromethyl, difluoromethyl, trifluorome tilo, fluormetox i, difluoromethoxy and trifluoromethoxy, or the Ra radical and an Rb radical, if present, which are linked to two adjacent carbon atoms of phenyl, can form a 5 or 6 membered heterocyclic or carbocyclic ring which is fused to the ring phenyl and which is unsubstituted or can carry 1, 2 or 3 roots selected from halogen, NO2, NH2, OH, CN, C1-C6 alkyl, fluorinated C1-C6 alkyl, C3-C6 cycloalkyl, fluorinated C3-C6 cycloalkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy, Hydroxyalkyl C1-C6, C1-C4-alkoxy-C2-C4-alkyl, Hydroxyalkoxy C1-C6, C1-C4-alkoxy-C2-C4-alkoxy, C1-C6 alkyl , C1-C6 alkyl fluorinated carbonyl, C1-C6amino alkyl, di-C1-C6amino alkyl, C1-C6 aminocarbonyl alkyl, di-C1-C6 aminocarbonyl alkyl, C1-C6 carbonylamino alkyl, C1-C6 fluorinated amino carbonyl alkyl, C1-C6 carbonyloxy alkyl , C1-C6 alkyl fluorinated carbonyloxy, C1-C6 alkoxy carbonyl, C1-C6 alkylthio, fluorinated C1-C6 alkylthio, C1-C6 alkyl sulfinyl, alkyl the C1-C6 fluorinated sulfinyl, C1-C6 alkyl sulfonyl and C1-C6 alkyl fluorinated sulfonyl, X is N or CH; R1 is H, C1-C4-alkyl, C3-C4-cycloalkyl, C3-C4-cycloalkylmethyl, C3-C4-alkenyl, fluorinated C1-C4 alkyl, fluorinated C3-C4 cycloalkyl, fluorinated C3-C4 cycloalkylmethyl, C3-C4 alkenyl fluorinated, formyl or C1-C3-alkylcarbonyl; R1a is H, C1-C4-alkyl, C3-C4-cycloalkyl, C3-C4-cycloalkylmethyl, C3-C4-alkenyl, fluorinated C1-C4 alkyl, fluorinated C3-C4 cycloalkyl, or C3- alkenyl Fluorinated C4; or R1 and R1a together are (CR6R740) r being r 3, 4 or 5; R2 and R2a are independently of each other H, fluorine, C1-C4-alkyl or fluorinated C1-C4 alkyl or R2a and R2 together can form a ring member (CR6R7) m being m 2, 3, 4 or 5; or R1a and R2a together are (CR6R7) n being n 2, 3 or 4, R3 is H or C1-C4-alkyl; R4, R5 independently of each other and regardless of their individual frequency are selected from H, C1-C3-alkyl, C1-C3-alkoxy and fluorinated C1-C3 alkyl; R6, R7 independently of each other and regardless of their individual frequency are selected from H, fluorine, C1-C4-alkyl and fluorinated C1-C4 alkyl; R8, R8a independently of each other are H, fluorine, C1-C4-alkyl or fluorinated C1-C4 alkyl or R8a and R8 together can form a ring member (CR6R7) q being q 2, 3, 4 or 5; or R1a and R8a together are (CR6R7) s being s 2 or 3; R9 is H, C1-C4-alkyl, fluorinated C1-C4 alkyl, C1-C4-alkoxy or fluorinated C1-C4 alkoxy; 10 and the physiologically tolerated acid addition salts of these compounds.

Description

Background of the invention 5

The present invention relates to novel aryloxyethylamine compounds. These compounds possess valuable therapeutic properties and are suitable, in particular, for the treatment of diseases that respond to the modulation of the dopamine D3 receptor.

Neurons obtain their information through receptors coupled to G proteins, among others. A large number of substances exert their effect via these receptors. One of them is dopamine. There are confirmed findings 10 regarding the presence of dopamine and its physiological function as a neurotransmitter. Disorders in the dopaminergic transmission system result in diseases of the central nervous system that include, for example, schizophrenia, depression and Parkinson's disease. These diseases, and others, are treated with drugs that interact with dopamine receptors.

Until 1990, two subtypes of dopamine receptors had been clearly defined pharmacologically, namely D1 and D2 receptors. More recently, a third subtype has been found, namely the D3 receptor which appears to mediate some antisychotic and antiparkinsonian effects (JC Schwartz et al., The Dopamine D3 Receptor as a Target for Antipsychotics, in Novel Antipsychotic Drugs, HY Meltzer, Ed. Raven Press, New York 1992, pages 135-144; M. Dooley et al., Drugs and Aging 1998, 12, 495-514, JN Joyce, Pharmacology and Therapeutics 2001, 90, pp. 231-59 "The Dopamina D3 Receptor as a Therapeutic Target for Antipsychotic and Antiparkinsonian Drugs "). twenty

Since then, dopamine receptors have been divided into two families. On the one hand, there is the D2 group, which consists of the D2, D3 and D4 receptors, and, on the other hand, the D1 group, consisting of the D1 and D5 receptors. While the D1 and D2 receptors are widely distributed, the D3 receptors appear to be expressed regioselectively. Thus, these receptors are preferentially found in the limbic system and in the protection regions of the mesolimbic system of dopamine, especially in nucleus accumbens, but also in other 25 regions, such as tonsils. Due to this comparatively regioselective expression, D3 receptors are seen as a target that has few side effects and it is assumed that while a selective D3 ligand would have the properties of known antisychotics, it would not have its neurological side effects mediated by the dopamine receptor. D2 (P. Sokoloff et al., Localization and Function of the D3 Dopamine Receptor, Arzneim. Forsch./Drug Res. 42 (1), 224 (1992); P. Sokoloff et al. Molecular Cloning and Characterization of a Novel Dopamina Receiver (D3) as a 30 Target for Neuroleptics, Nature, 347, 146 (1990)).

WO 99/58499 discloses phenylethylamines substituted with phenylsulfonamide having an affinity for the dopamine D3 receptor.

WO 2006/040179 published in an intermediate form describes aminoethyl aromatic compounds where the aromatic structural unit carries an arylsulfonylmethyl or arylsulfonylamino group in position 4 with respect to the aminoethyl group. The compounds are mentioned as useful for the treatment of disorders that respond to the modulation of the dopamine D3 receptor.

Summary of the Invention

The invention is based on the object of providing compounds that act as highly selective dopamine D3 receptor ligands. This objective is surprisingly achieved by means of the aryloxyethylamine compounds of formula I

where

Ar is phenyl or a 5- or 6-membered heteroaromatic aromatic radical linked by C, where Ar can carry a Ra radical and where Ar can also carry 1 or 2 Rb radicals;

Ra is selected from the group consisting of C1-C6 alkyl, fluorinated C1-C6 alkyl, C2-C6 alkenyl, C2-C6 fluorinated alkenyl, C3-C6 cycloalkyl, fluorinated C3-C6 cycloalkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy , C1-C6 hydroxyalkyl, C1-C4-C1-C6 alkoxy, C1-C6 hydroxyalkoxy, C1-C4 alkoxy-C1-C6 alkoxy, COOH, NR4R5, CH2NR4R5, ONR4R5, NHC (O) NR4R5, 5 C (O) NR4R5, SO2NR4R5, C1-C6 alkylcarbonyl, fluorinated C1-C6 alkyl, C1-C6 alkylcarbonylamino, C1-C6 alkyl, fluorinated amino carbon, C1-C6 alkylcarbonyloxy, C1-C6 alkylcarbonyloxy fluorinated, C1-C6 alkoxycarbonyl, C1-C6 fluorinated alkoxycarbonyl, C1-C6 alkylthio, fluorinated C1-C6 alkylthio, C1-C6 alkyl sulfinyl, C1-C6 alkyl fluorinated sulfinyl, C1-C6 alkyl sulfonyl, C1-C6 fluorinated alkyl sulfonyl, phenylsulfonyl, phenyl, phenoxy, benzyloxy, pyridine -2-yloxy and a 3- to 7-membered heterocyclic radical, where the phenyl groups, the pyridyl group and the heterocyclyl group in the last six mentioned radicals they can carry 1, 2, 3 or 4 radicals selected from halogen, cyano, OH, oxo, CN, and a Raa radical, where Raa is selected from C1-C6 alkyl, fluorinated C1-C6 alkyl, C2-C6 alkenyl, fluorinated alkenyl C2-C6, C3-C6 cycloalkyl, fluorinated C3-C6 cycloalkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy, C1-C6 hydroxyalkyl, C1-C4 alkyl-C1-C6 alkyl, Hydroxyalkoxy C1-C6, C1-C4 alkoxy C1-C6 alkoxy, COOH, NR4R5, CH2NR4R5, ONR4R5, NHC (O) NR4R5, C (O) NR4R5, SO2NR4R5, C1-C6 alkylcarbonyl, C1-C6 alkyl fluorinated carbonyl, C1-C6 alkylcarbonyl, C1-15 alkyl C6 fluorinated amino carbonyl, C1-C6oxy alkylcarbonyl, C1-C6 alkyl fluorinated carbonyloxy, C1-C6-alkoxycarbonyl, C1-C6 fluorinated alkoxycarbonyl, C1-C6 alkyl, fluorinated C1-C6 alkylthio, C1-C6 alkyl sulfinyl, C1- alkylsulfinyl C6 fluorinated, C1-C6 alkyl sulfonyl, C1-C6 alkyl fluorinated sulfonyl,

each Rb is selected from halogen, cyano, nitro, OH, methyl, methoxy, fluoromethyl, difluoromethyl, trifluoromethyl, fluoromethoxy, difluoromethoxy and trifluoromethoxy, or

the Ra radical and an Rb radical, if present, which are linked to two adjacent carbon atoms of phenyl, can form a 5- or 6-membered heterocyclic or carbocyclic ring which is fused to the phenyl ring and which is unsubstituted or it may carry 1, 2 or 3 selected roots of halogen, NO2, NH2, OH, CN, C1-C6 alkyl, fluorinated C1-C6 alkyl, C3-C6 cycloalkyl, fluorinated C3-C6 cycloalkyl, C1-C6 alkoxy, C1 alkoxy -C6 fluorinated, Hydroxyalkyl C1-C6 C1-C4- alkoxy-C2-C4-alkyl, Hydroxyalkoxy C1-C6, C1-C4-alkoxy-C2-C4-alkoxy, C1-C6 alkylcarbonyl, C1-C6 alkyl fluorinated carbonyl, C1-C6-alkyl, di-C1-C6-alkylamino, C1-C6-alkylcarbonyl, di-C1-C6-alkylcarbonyl, C1-C6-alkyl alkyl, C1-C6 alkyl-fluorinated amino, C1-C6oxy-alkylcarbonyl, fluorinated-C1-C6 alkyl, C1-C6 alkoxy carbonyl, C1-C6 alkylthio, fluorinated C1-C6 alkylthio, C1-C6 alkyl sulfinyl, C1-C6 alkyl fluorinated sulfinyl, C1- alkyl C6 sulfonyl and C1-C6 alkyl fluorinated sulfonyl,

X is N or CH; 30

R1 is H, C1-C4-alkyl, C3-C4-cycloalkyl, C3-C4-cycloalkylmethyl, C3-C4-alkenyl, fluorinated C1-C4 alkyl, fluorinated C3-C4 cycloalkyl, fluorinated C3-C4 cycloalkylmethyl, C3-C4 alkenyl fluorinated, formyl or C1-C3-alkylcarbonyl;

R1a is H, C1-C4-alkyl, C3-C4-cycloalkyl, C3-C4-cycloalkylmethyl, C3-C4-alkenyl, fluorinated C1-C4 alkyl, fluorinated C3-C4 cycloalkyl, or C3- alkenyl C3- Fluorinated C4; or

R1 and R1a together are (CR6R7) r being r 3, 4 or 5; 35

R2 and R2a are independently of each other H, fluorine, C1-C4-alkyl or fluorinated C1-C4 alkyl or R2a and R2 together can form a ring member (CR6R7) m being m 2, 3, 4 or 5; or

R1a and R2a together are (CR6R7) n being n 2, 3 or 4,

R3 is H or C1-C4-alkyl;

R4, R5 independently of each other and independently of their individual frequency are selected from H, C1-C3-40 alkyl, C1-C3-alkoxy and fluorinated C1-C3 alkyl;

R6, R7 independently of each other and regardless of their individual frequency are selected from H, fluorine, C1-C4-alkyl and fluorinated C1-C4 alkyl;

R8, R8a independently of each other are H, fluorine, C1-C4-alkyl or fluorinated C1-C4 alkyl or R8a and R8 together can form a ring member (CR6R7) q being q 2, 3, 4 or 5; or 45

R1a and R8a together are (CR6R7) s being s 2 or 3; and

R9 is H, C1-C4-alkyl, fluorinated C1-C4 alkyl, C1-C4-alkoxy or fluorinated C1-C4 alkoxy;

and the physiologically tolerated acid addition salts of these compounds.

The present invention therefore relates to aryloxyethylamine compounds of the general formula I and their physiologically tolerated acid addition salts.

The present invention also relates to a pharmaceutical composition comprising at least one aryloxyethylamine compound of the formula I and / or at least one physiologically tolerated acid addition salt of I, when appropriate together with the physiologically acceptable carriers and / or auxiliary substances. . 5

The present invention also relates to a method for treating disorders that respond to the influence of dopamine D3 receptor antagonists or dopamine D3 agonists, said method comprising administering an effective amount of at least one aryloxyethylamine compound of the formula I and / or at least one physiologically tolerated acid addition salt of I to a subject that so requires.

Detailed Description of the Invention 10

Diseases that respond to the influence of dopamine D3 receptor antagonists or agonists include, in particular, disorders and diseases of the central nervous system, in particular affective disturbances, neurotic disturbances, stress disturbances and somatoform disturbances and psychosis, especially schizophrenia and depression and, in addition, renal function disturbances, in particular, renal function disturbances caused by diabetes mellitus (see WO 00/67847). fifteen

According to the invention, at least one compound of the general formula I having the meanings mentioned in its presentation is used to treat the indications mentioned above. Since the compounds of the formula I of a given constitution may exist in different spatial arrangements, for example, if they have one or more centers of asymmetry, polysubstituted rings or double bonds, or as different tautomers, it is also possible to use enantiomeric mixtures, in particular racemates, diastereomeric mixtures and tautomeric mixtures, preferably, however, the essentially pure enantiomers, diastereomers and respective tautomers of the compounds of the formula I and / or their salts.

It is also possible to use physiologically tolerated salts of the compounds of formula I, especially acid addition salts with physiologically tolerated acids. Examples of suitable physiologically tolerated organic and inorganic acids are hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, C1-C4-alkylsulfonic acids, such as methanesulfonic acid, sulfonic aromatic acids, such as benzenesulfonic acid and toluenesulfonic acid, oxalic acid, maleic acid, fumaric acid, lactic acid, tartaric acid, adipic acid and benzoic acid. Other usable acids are described in Fortschritte der Arzneimittelforschung [Advances in drug research], Volume 10, pages 224 ff., Birkhäuser Verlag, Basel and Stuttgart, 1966.

The organic structural units mentioned in the previous definitions of the variables are - like the term 30 halogen - collective terms for individual listings of individual group members. The prefix Cn-Cm indicates in each case the possible number of carbon atoms in the group.

The term halogen denotes in each case fluorine, bromine, chlorine or iodine, in particular fluorine or chlorine.

C1-C4 Alkyl (and in the same way in C1-C4 hydroxyalkyl, C1-C6 alkoxy-C1-C4-alkyl, C1-C4 alkylcarbonyl, C1-C4 alkylcarbonylamino, C1-C4 alkylcarbonyloxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl etc.) is a straight or branched chain alkyl group having 1 to 4 carbon atoms. Examples of an aqluyl group are methyl, ethyl, n-propyl, isopropyl, n-butyl, 2-butyl, iso-butyl or tert-butyl.

C1-C6 Alkyl (and in the same way in C1-C6 hydroxyalkyl, C1-C6 alkoxy-C1-C4-alkyl, C1-C6 alkylcarbonyl, C1-C6 alkylcarbonylamino, C1-C6 alkylcarbonyloxy, C1-C6 alkylthio, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl etc.) is a straight or branched chain alkyl group having 1 to 6 carbon atoms. Examples include C1-C4 alkyl as mentioned above and also pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1,1-dimethylpropyl, 1,2- dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3, 3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl and 1-ethyl-2-methylpropyl;

C1-C6 fluorinated alkyl (and in the same way in fluorinated C1-C6 alkylcarbonyl, fluorinated C1-C6 alkylcarbonylamino, fluorinated C1-C6 alkylcarbonyloxy, fluorinated C1-C6 alkyl, fluorinated C1-C6 alkyl sulphyl, fluorinated C1-C6 alkylsulphonyl etc .) is a straight or branched chain alkyl group having 1 to 6, in particular 1 to 4 carbon atoms, more preferably 1 to 3 carbon atoms, where at least one, eg 1, 2, 3, 4 or all hydrogen atoms are replaced by a fluorine atom, such as fluoromethyl, difluoromethyl, trifluoromethyl, (R) -1-fluoroethyl, (S) -1-fluoroethyl, 2-fluoroethyl, 1,1-difluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, (R) -1-fluoropropyl, (S) -1-fluoropropyl, 2-50 fluoropropyl, 3-fluoropropyl, 1,1-difluoropropyl , 2,2-difluoropropyl, 3,3-difluoropropyl, 3,3,3-trifluoropropyl, (R) -2-fluoro-1-methylethyl, (S) -2-fluoro-1-methylethyl, (R-2, 2-Difluoro-1-methyl ethyl, (S) -2,2-difluoro-1-methyl ethyl, (R) -1,2-difluoro-1-methyl ethyl, (S) -1,2-difluoro-1-methyl ethyl, (R) -2,2,2-trifluoro-1-methyl ethyl, (S) -2,2,2-trifluoro-1-methyl ethyl, 2-fluoro-1- (fluoromethyl) ethyl, 1- (difluoromethyl) -2 , 2-difluoroethyl, (R) -1-fluorobutyl, (S) -1-fluorobutyl, 2-fluorobutyl, 3-fluorobutyl, 4-fluorobutyl, 1,1-difluorobutyl, 2,2-difluorobutyl, 3,3-difluorobutyl , 4,4-difluorobutyl, 4,4,4-trifluorobutyl, etc .; 55

C3-C6 branched alkyl is alkyl having from 3 to 6 carbon atoms with at least one being a secondary or tertiary carbon atom. Examples are isopropyl, tert.-butyl, 2-butyl, isobutyl, 2-pentyl, 2-hexyl, 3-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl 1-methyl-1-ethylpropyl.

C1-C6 Alkoxy (and similarly in C1-C6 alkoxycarbonyl, C1-C6 alkoxy-C1-C4 alkyl, C1-C6 alkoxy-C1-C4 alkoxy and C1-C6 hydroxyalkoxy) is a straight or branched chain alkyl group which it has 1 to 6, in particular 1 to 4 carbon atoms, which is linked to the rest of the molecule through an oxygen atom. Examples include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, 2-butoxy, iso-butoxy, tert.-butoxy, pentyloxy, 1-methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 2,2-dimethylpropoxy, 1 -ethylpropoxy, hexyloxy, 1,1-dimethylpropoxy, 1,2-dimethylpropoxy, 1-methylpentyloxy, 2-methylpentyloxy, 3-methylpentyloxy, 4-methylpentyloxy, 1,1-dimethylbutyloxy, 1,2-dimethylbutyloxy, 1,3-dimethylbutyloxy , 2,2-dimethylbutyloxy, 2,3-dimethylbutyloxy, 3,3-dimethylbutyloxy, 1-ethylbutyloxy, 2-ethylbutyloxy, 1,1,2-trimethylpropoxy, 1,2,2-trimethylpropoxy, 1-ethyl-1-10 methylpropoxy and 1-ethyl-2-methylpropoxy;

Fluorinated C1-C6 alkoxy (and similarly in fluorinated C1-C6 alkoxycarbonyl) is a straight or branched alkoxy group having 1 to 6, in particular 1 to 4 carbon atoms, where at least one, e.g. 1, 2, 3, 4 or all hydrogen atoms are replaced by a fluorine atom, such as fluoromethoxy, difluoromethoxy, trifluoromethoxy, (R) -1- fluoroethoxy, (S) -1-fluoroethoxy, 2-fluoroethoxy, 1,1-difluoroethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, (R) -1-15 fluoropropoxy, (S) -1-fluoropropoxy, 2-fluoropropoxy, 3-fluoropropoxy, 1,1-difluoropropoxy , 2,2-difluoropropoxy, 3,3-difluoropropoxy, 3,3,3-trifluoropropoxy, (R) -2-fluoro-1-methylethoxy, (S) -2-fluoro-1-methylethoxy, (R) -2 , 2-difluoro-1-methylethoxy, (S) -2,2-difluoro-1-methylethoxy, (R) -1,2-difluoro-1-methylethoxy, (S) -1,2-difluoro-1-methylethoxy , (R) -2,2,2-trifluoro-1-methylethoxy, (S) -2,2,2-trifluoro-1-methylethoxy, 2-fluoro-1- (fluoromethyl) ethoxy, 1- (diftuoromethyl) - 2,2-difluoroethoxy, (R) -1-fluorobutoxy, (S) -1-fluorobutoxy, 2-fluorobutoxy, 3-fluorobutoxy, 4-fluorobutoxy, 1,1-difluorobutoxy, 2,2-difluorobutoxy, 3,3- difluorobutoxy, 4.4-20 difluorobutoxy, 4,4,4-trifluorobutoxy, etc .;

C3-C6 Cycloalkyl is a cycloaliphatic radical having 3 to 6 C atoms, such as cyclopropyl, cyclobutyl and cyclopentyl. The cycloalkyl radical may be unsubstituted or may carry 1, 2, 3 or 4 C1-C4 alkyl radicals, preferably a methyl radical. An alkyl radical is preferably located at position 1 of the cycloalkyl radical, such as in 1-methylcyclopropyl or 1-methylcyclobutyl. 25

C3-C6 fluorinated cycloalkyl is a cycloaliphatic radical having 3 to 6 C atoms, such as cyclopropyl, cyclobutyl and cyclopentyl, where at least one, e.g. 1, 2, 3, 4 or all of the hydrogen atoms are replaced by a fluorine atom, such as 1-fluorocyclopropyl, 2-fluorocyclopropyl, 2,2-difluorocyclopropyl, 1,2-difluorocyclopropyl, 2,3-difluorocyclopropyl, pentafluorocyclopropyl, 1-fluorocyclobutyl, 2-fluorocyclobutyl, 3-fluorocyclobutyl, 2,2-difluorocyclobutyl, 3,3-difluorocyclobutyl, 1,2-difluorocyclobutyl, 1,3-difluorocyclobutyl, 2,3-difluorocyclobutyl, 2,4-30 difluorobutyl, 2,4-30 difluorobutyl , or 1,2,2-trifluorocyclobutyl.

C3-C6 cycloalkylmethyl is methyl which carries a cycloaliphatic radical having 3 to 6 C atoms as mentioned above

C3-C6 fluorinated cycloalkylmethyl is methyl which carries a cycloaliphatic radical having 3 to 6 C atoms, where at least one, e.g. 1, 2, 3, 4 or all hydrogen atoms are replaced by a fluorine atom. 35

C2-C6 alkenyl is a hydrocarbon radical with a unique unsaturation having 2, 3, 4, 5 or 6 C atoms, e.g. vinyl, allyl (2-propen-1-yl), 1-propen-1-yl, 2-propen-2-yl, metalyl (2-methylprop-2-en-1-yl) and the like. C3-C4-Alkenyl is, in particular, allyl, 1-methylprop-2-en-1-yl, 2-buten-1-yl, 3-buten-1-yl, metalyl, 2-penten-1-yl, 3-penten-1-yl, 4-penten-1-yl, 1-methylbut-2-en-1-yl or 2-ethylprop-2-en-1-yl.

C2-C6 fluorinated alkenyl is a hydrocarbon radical with a unique unsaturation having 2, 3, 4, 5 or 6 Atoms of C, 40 where at least one, e.g. 1, 2, 3, 4 or all hydrogen atoms are replaced by a fluorine atom, such as 1-fluorovinyl, 2-fluorovinyl, 2,2-fluorovinyl, 3,3,3-fluoropropenyl, 1,1- difluoro-2-propenyl 1-fluoro-2-propenyl and the like.

C1-C6 hydroxyalkyl is an alkyl radical having 1 to 6 carbon atoms as defined above, where a hydrogen atom is replaced by hydroxy. As examples, hydroxymethyl, 2-hydroxyethyl, 1-45 hydroxyethyl, 3-hydroxypropyl, 2-hydroxypropyl, 1-methyl-1-hydroxyethyl and the like can be mentioned.

C1-C6 hydroxyalkoxy is an alkoxy radical having from 1 to 6, preferably from 2 to 4 carbon atoms as defined above, where a hydrogen atom is replaced by hydroxy. As examples there may be mentioned 2-hydroxyethoxy, 3-hydroxypropoxy, 2-hydroxypropoxy, 1-methyl-2-hydroxyethoxy and the like.

C1-C6 alkoxy-C1-C4-alkyl is an alkyl radical having from 1 to 4 carbon atoms as defined above, where a hydrogen atom is replaced by C1-C6 alkoxy. As examples, there may be mentioned methoxymethyl, 2-methoxyethyl, 1-methoxyethyl, 3-methoxypropyl, 2-methoxypropyl, 1-methyl-1-methoxyethyl, ethoxymethyl, 2-ethoxyethyl, 1-ethoxyethyl, 3-ethoxypropyl, 2-ethoxypropyl, 1 -methyl-1-ethoxyethyl and the like.

C1-C6 alkoxy-C1-C4-alkoxy is an alkoxy radical having 1 to 4 carbon atoms as defined above, where a hydrogen atom is replaced by C1-C6 alkoxy. As examples, there may be mentioned methoxymethoxy, 2-methoxyethoxy, 1-methoxyethoxy, 3-methoxypropoxy, 2-methoxypropoxy, 1-methyl-1-methoxyethoxy, ethoxymethoxy, 2-ethoxyethoxy, 1-ethoxyethoxy, 3-ethoxypropoxy, 2-ethoxy, 1-ethoxy -methyl-1-ethoxyethoxy and the like.

C1-C6 alkylcarbonyl is a radical of the formula R-C (O) -, where R is an alkyl radical having 1 to 6 carbon atoms as defined above. As examples there may be mentioned acetyl, propionyl, n-butyryl, 2-methylpropionyl, pivalyl and the like.

C1-C6 alkylcarbonylamino is a radical of the formula R-C (O) -NH-, where R is an alkyl radical having 1 to 6 carbon atoms as defined above. As examples there may be mentioned acetamido, propionamido, n-butyramido, 2-methylpropionamido, 2,2-dimethylpropionamido and the like. 10

C1-C6 alkylcarbonyloxy is a radical of the formula R-C (O) -O-, where R is an alkyl radical having 1 to 6 carbon atoms as defined above. As examples there may be mentioned acetyloxy, propionyloxy, n-butyryloxy, 2-methylpropionyloxy, 2,2-dimethylpropionyloxy and the like.

C1-C6 alkylthio is a radical of the formula R-S-, where R is an alkyl radical having 1 to 6 carbon atoms as defined above. As examples, there may be mentioned methylthio, ethylthio, propylthio, butylthio, pentylthio, 1-methylbutylthio, 2-15 methylbutylthio, 3-methylbutylthio, 2,2-dimethylpropylthio, 1-ethylpropylthio, hexylthio, 1,1-dimethylpropylthio, 1,2- dimethylpropylthio, 1-methylpentylthio, 2-methylpentylthio, 3-methylpentylthio, 4-methylpentylthio, 1,1-dimethylbutylthio, 1,2-dimethylbutylthio, 1,3-dimethylbutylthio, 2,2-dimethylbutylthio, 2,3-dimethylbutylthio, 3, 3-dimethylbutylthio, 1-ethylbutylthio, 2-ethylbutylthio, 1,1,2-trimethylpropylthio, 1,2,2-trimethylpropylthio, 1-ethyl-1-methylpropyl and 1-ethyl-2-methylpropyl;

C1-C6 alkylsulfinyl is a radical of the formula R-S (O) -, where R is an alkyl radical having 1 to 6 carbon atoms as defined above. As examples, there can be mentioned methylsulfinyl, ethylsulfinyl, propylsulfinyl, butylsulfinyl, pentylsulfinyl, 1-methylbutyl sulfinyl, 2-methylbutyl sulfinyl, 3-methylbutyl sulfinyl, 2,2-dimethylpropylsulfinyl, 1-ethylpropylsulfinyl-1,2-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-methyl-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-dimethyl-methyl-dimethyl ester-methylsulfinyl examples. , 1-methylpentylsulfinyl, 2-methylpentylsulfinyl, 3-methylpentylsulfinyl, 4-methylpentylsulfinyl, 1,1-dimethylbutylsulfinyl, 1,2-dimethylbutyl sulfinyl, 1,3-dimethylbutylfinyl, 2,2-dimethylbutyl sulfinyl, 2,3-dimethylbutyl sulfinyl, 3,3 -dimethylbutylsulfinyl, 1-ethylbutylsulfinyl, 2-25 ethylbutylsulfinyl, 1,1,2-trimethylpropylsulfinyl, 1,2,2-trimethylpropylsulfinyl, 1-ethyl-1-methylpropyl and 1-ethyl-2-methylpropyl;

C1-C6 alkylsulfonyl is a radical of the formula R-S (O) 2-, where R is an alkyl radical having 1 to 6 carbon atoms as defined above. As examples, there can be mentioned methylsulfonyl, ethylsulfonyl, propylsulfonyl, butylsulfonyl, pentylsulfonyl, 1-methylbutyl sulfonyl, 2-methylbutyl sulfonyl, 3-methylbutyl sulfonyl, 2,2-dimethylpropylsulfonyl, 1-ethylpropylsulfonyl, 1,1-dimethylsulfonyl-1,1-dimethylsulfonyl-1,1-dimethyl-sulfonyl-1,2-dimethyl-sulfonyl-1,1-dimethyl-sulfonyl-1,2-dimethyl-sulfonyl-1,1-dimethyl-sulfonyl-1,2-dimethyl-sulfonyl-1,2-dimethyl-sulfonyl-1,2-dimethyl-sulfonyl-1,2-dimethyl-sulfonyl-1,2-dimethylsulfonyl-1,2-dimethylsulphonyl ester. , 1-methylpentylsulfonyl, 2-30 methylpentylsulfonyl, 3-methylpentylsulfonyl, 4-methylpentylsulfonyl, 1,1-dimethylbutyl sulfonyl, 1,2-dimethylbutyl sulfonyl, 1,3-dimethylbutyl sulfonyl, 2,2-dimethylbutyl sulfonyl, 2,3-dimethylbutyl sulfonyl, 3 3-dimethylbutyl sulfonyl, 1-ethylbutyl sulfonyl, 2-ethylbutyl sulfonyl, 1,1,2-trimethylpropylsulfonyl, 1,2,2-trimethylpropylsulfonyl, 1-ethyl-1-methylpropyl and 1-ethyl-2-methylpropyl; fluorinated C1-C6 alkylcarbonyl is a radical of the formula R-C (O) -, where R is a fluorinated alkyl radical having 1 to 6 carbon atoms as defined above. As examples, fluoroacetyl, difluoroacetyl, trifluoroacetyl, (R) -1-fluoroethylcarbonyl, (S) -1-fluoroethylcarbonyl, 2-fluoroethylcarbonyl, 1,1-difluoroethylcarbonyl, 2,2-difluoroethylcarbonyl, 2,2,2- trifluoroethylcarbonyl, (R) -1-fluoropropylcarbonyl, (S) -1-fluoropropylcarbonyl, 2-fluoropropylcarbonyl, 3-fluoropropylcarbonyl, 1,1-difluoropropylcarbonyl, 2,2-difluoropropylcarbonyl, 3,3-difluoropropylcarbonyl, 3,3,3- trifluoropropylcarbonyl, (R) -2-fluoro-1-methyl ethylcarbonyl, (S) -2-fluoro-1-methyl ethylcarbonyl, (R) -2,2-difluoro-1-methyl ethylcarbonyl, (S) -2,2-difluoro- 1-methyl ethylcarbonyl, (R) -1,2-difluoro-1-methyl ethylcarbonyl, (S) -1,2-40 difluoro-1-methyl ethylcarbonyl, (R) -2,2,2-trifluoro-1-methyl ethylcarbonyl, ( S) -2,2,2-trifluoro-1-methyl ethylcarbonyl, 2-fluoro-1- (fluoromethyl) ethylcarbonyl, 1- (difluoromethyl) -2,2-difluoroethylcarbonyl, (R) -1-fluorobutylcarbonyl, (S) - 1-fluorobutylcarbonyl, 2-fluorobutylcarbonyl,

3-fluorobutylcarbonyl, 4-fluorobutylcarbonyl, 1,1-difluorobutylcarbonyl, 2,2-difluorobutylcarbonyl, 3,3-difluorobutylcarbonyl, 4,4-difluorobutylcarbonyl, 4,4,4-trifluorobutylcarbonyl, etc .; Four. Five

fluorinated C1-C6 alkylcarbonylamino is a radical of the formula R-C (O) -NH-, where R is a fluorinated alkyl radical having 1 to 6 carbon atoms as defined above. Examples of fluoroacetamido, difluoroacetamido, trifluoroacetamido, (R) -1-fluoroethylcarbonylamino, (S) -1-fluoroethylcarbonylamino, 2-fluoroethylcarbonylamino, 1,1-difluoroethylcarbonylamino, 2,2-difluoroethylcarbonylamino, 2,2,2-trifthylcarbonylamino , (R) -1-fluoropropylcarbonylamino, 50

(S) -1-fluoropropylcarbonylamino, 2-fluoropropylcarbonylamino, 3-fluoropropylcarbonylamino, 1,1-difluoropropylcarbonylamino, 2,2-difluoropropylcarbonylamino, 3,3-difluoropropylcarbonylamino, 3,3,3-trifluoropropylcarbonylamino, (R) -2-fluoro- 1-methyl ethylcarbonylamino, (S) -2-fluoro-1-methyl ethyl carbonylamino, (R) -2,2-difluoro-1-methyl ethylcarbonylamino, (S) -2,2-difluoro-1-methyl ethylcarbonylamino, (R) -1, 2-Difluoro-1-methyl ethylcarbonylamino, (S) -1,2-difluoro-1-methyl ethylcarbonylamino, (R) -2,2,2-trifluoro-1-methyl ethylcarbonylamino, (S) -2,2,2-trifluoro- 1-Methyl ethylcarbonylamino, 2-fluoro-1- (fluoromethyl) ethylcarbonylamino, 1-55 (difluoromethyl) -2,2-difluoroethylcarbonylamino, (R) -1-fluorobutylcarbonylamino, (S) -1-fluorobutylcarbonylamino, 2-

fluorobutylcarbonylamino, 3-fluorobutylcarbonylamino, 4-fluorobutylcarbonylamino, 1,1-difluorobutylcarbonylamino, 2,2-difluorobutylcarbonylamino, 3,3-difluorobutylcarbonylamino,

4,4-difluorobutylcarbonylamino, 4,4,4-trifluorobutylcarbonylamino, etc.,

fluorinated C1-C6 alkylcarbonyloxy is a radical of the formula RC (O) -O-, where R is a fluorinated alkyl radical having 1 to 6 carbon atoms as defined above fluoroacetyl, difluoroacetyl, trifluoroacetyl, (R) -1-5 fluoroethylcarbonyloxy, (S) -1-fluoroethylcarbonyloxy, 2-fluoroethylcarbonyloxy, 1,1-difluoroethylcarbonyloxy, 2,2-difluoroethylcarbonyloxy, 2,2,2-trifluoroethylcarbonyloxy, (R) -1-fluoropropylcarbonyloxy, (S) - 1-fluoropropylcarbonyloxy, 2-fluoropropylcarbonyloxy, 3- fluoropropylcarbonyloxy, 1,1-difluoropropylcarbonyloxy, 2,2-difluoropropylcarbonyloxy, 3,3-difluoropropylcarbonyloxy, 3,3,3-trifluoropropylcarbonyloxy, (R) -2-fluorocarbonyl-1-methylcarbonyl (S) -2-fluoro-1-methyl ethylcarbonyloxy, (R) -2,2-difluoro-1-methyl ethylcarbonyloxy, (S) -2,2-difluoro-1-methyl ethylcarbonyloxy, (R) -1,2-difluoro- 1-10 methyl ethylcarbonyloxy, (S) -1,2-difluoro-1-methyl ethylcarbonyloxy, (R) -2,2,2-trifluoro-1-methyl ethylcarbonyloxy, (S) -2,2,2-trifluoro-1 -methylethylcarbonyloxy, 2-fluoro-1- (fluoromet il) ethylcarbonyloxy, 1- (difluoromethyl) -2,2-difluoroethylcarbonyloxy, (R) -1-fluorobutylcarbonyloxy, (S) -1-fluorobutylcarbonyloxy, 2-fluorobutylcarbonyloxy, 3-fluorobutylcarbonyloxy, 4-fluorobutylcarbonyloxy, 1,1-difluorobutoxy 2,2-Difluorobutylcarbonyloxy, 3,3-difluorobutylcarbonyloxy, 4,4-difluorobutylcarbonyloxy, 4,4,4-trifluorobutylcarbonyloxy, etc .; fifteen

fluorinated C1-C6 alkylthio is a radical of the formula R-S-, where R is a fluorinated alkyl radical having 1 to 6 carbon atoms as defined above. Examples include fluoromethylthio, difluoromethylthio, trifluoromethylthio, (R) -1-fluoroethylthio, (S) -1-fluoroethylthio, 2-fluoroethylthio, 1,1-difluoroethylthio, 2,2-difluoroethylthio, 2,2,2-trifluoroethylthio , (R) -1-fluoropropylthio, (S) -1-fluoropropylthio, 2-fluoropropylthio, 3-fluoropropylthio, 1,1-difluoropropylthio, 2,2-difluoropropylthio, 3,3-difluoropropylthio, 3,3,3-trifluoropropylthio , (R) -2-fluoro-1-methyl ethylthio, (S) -2-fluoro-1-methyl ethylthio, (R) -2,2-20 difluoro-1-methyl ethylthio, (S) -2,2-difluoro- 1-methyl ethylthio, (R) -1,2-difluoro-1-methyl ethylthio, (S) -1,2-difluoro-1-methyl ethylthio, (R) -2,2,2-trifluoro-1-methyl ethylthio, (S ) -2,2,2-trifluoro-1-methyl ethylthio, 2-fluoro-1- (fluoromethyl) ethylthio, 1- (difluoromethyl) -2,2-difluoroethylthio, (R) -1-fluorobutylthio, (S) -1 -fluorobutylthio, 2-fluorobutylthio, 3-fluorobutylthio, 4-fluorobutylthio, 1,1-difluorobutylthio, 2,2-difluorobutylthio, 3,3-difluorobutylthio, 4,4-difluorobutylthio, 4,4,4-trifluorobutylthio, etc .;

fluorinated C1-C6 alkylsulfinyl is a radical of the formula R-S (O) -, where R is a fluorinated alkyl radical having from 1 to 25 carbon atoms as defined above. As examples, fluoromethylsulfinyl, difluoromethylsulfinyl, trifluoromethylsulfinyl, (R) -1-fluoroethylsulfinyl, (S) -1-fluoroethylsulfinyl, 2-fluoroethylsulfinyl, 1,1-difluoroethylsulfinyl, 2,2-difluoroethylsulfinyl, 2,2,2-trilsulfinyl, 2,2,2-trils , (R) -1-fluoropropylsulfinyl, (S) -1-fluoropropylsulfinyl, 2-fluoropropylsulfinyl, 3-fluoropropylsulfinyl,

1,1-difluoropropylsulfinyl, 2,2-difluoropropylsulfinyl, 3,3-difluoropropylsulfinyl, 3,3,3-trifluoropropylsulfinyl, (R) -2-fluoro-1-30 methylethylsulfinyl, (S) -2-fluoro-1-methylethylsulfinyl , (R) -2,2-difluoro-1-methylethylsulfinyl, (S) -2,2-difluoro-1-methylethylsulfinyl, (R) -1,2-difluoro-1-methylethylsulfinyl, (S) -1,2 -difluoro-1-methylethylsulfinyl, (R) -2,2,2-trifluoro-1-methylethylsulfinyl, (S) -2,2,2-trifluoro-1-methylethylsulfinyl, 2-fluoro-1- (fluoromethyl) ethylsulfinyl, 1- (difluoromethyl) -2,2-difluoroethylsulfinyl, (R) -1-fluorobutylsulfinyl, (S) -1-fluorobutylsulfinyl, 2-fluorobutylsulfinyl, 3-fluorobutylsulfinyl, 4-fluorobutylsulfinyl, 1,1-difluorobutylsulfinyl, 2,2- difluorobutylsulfinyl, 3,3-difluorobutylsulfinyl, 4,4-difluorobutylsulfinyl, 4,4,4-trifluorobutylsulfinyl, etc .; 35

fluorinated C1-C6 alkylsulfonyl is a radical of the formula R-S (O) 2-, where R is a fluorinated alkyl radical having 1 to 6 carbon atoms as defined above. Examples of fluoromethylsulfonyl, difluoromethylsulfonyl, trifluoromethylsulfonyl, (R) -1-fluoroethylsulfonyl, (S) -1-fluoroethylsulfonyl, 2-fluoroethylsulfonyl, 1,1-difluoroethylsulfonyl, 2,2-difluoroethylsulfonyl, 2,2,2-trifluoroethyl , (R) -1-fluoropropylsulfonyl, (S) -1-fluoropropylsulfonyl, 2-fluoropropylsulfonyl, 3-fluoropropylsulfonyl, 1,1-difluoropropylsulfonyl, 2,2-difluoropropylsulfonyl, 3,3-difluoropropylsulfonyl, 3,3,3- trifluoropropylsulfonyl, (R) -2-fluoro-1-methylethylsulfonyl, (S) -2-fluoro-1-methylethylsulfonyl, (R) -2,2-difluoro-1-methylethylsulfonyl, (S) -2,2-difluoro- 1-Methylethylsulfonyl, (R) -1,2-difluoro-1-methylethylsulfonyl, (S) -1,2-difluoro-1-methylethylsulfonyl, (R) -2,2,2-trifluoro-1-methylethylsulfonyl, (S ) -2,2,2-trifluoro-1-methylethylsulfonyl, 2-fluoro-1- (fluoromethyl) ethyl sulfonyl, 1- (difluoromethyl) -2,2-difluoroethylsulfonyl, (R) -1-fluorobutyl sulfonyl, (S) -1 -fluorobutyl sulfonyl, 2-fluorobutyl sulfonyl, 3-fluorobutyl sulfonyl, 4-fluorobu tilsulfonyl, 1,1-difluorobutyl sulfonyl, 2,2-difluorobutyl sulfonyl, 3,3-45 difluorobutyl sulfonyl, 4,4-difluorobutyl sulfonyl, 4,4,4-trifluorobutyl sulfonyl, etc.

3 to 7-membered heterocyclic radicals comprise saturated heterocyclic radicals, which generally have 3-, 4-, 5-, 6- or 7 ring-forming atoms (ring members), unsaturated non-aromatic heterocyclic radicals, which have in generally 5-, 6- or 7 ring-forming atoms, and heteroaromatic radicals, which generally have 5-, 6- or 7 ring-forming atoms. Heterocyclic radicals can be linked through a carbon atom (Link with C) or a nitrogen atom (Link with N). Preferred heterocyclic radicals comprise 1 nitrogen atom as a ring member atom and optionally 1, 2 or 3 additional heteroatoms as ring members, which are independently selected from each other from O, S and N. Similarly preferred heterocyclic radicals they comprise 1 heteroatom as a ring member, which is selected from O, S and N, and optionally 1, 2 or 3 additional nitrogen atoms as ring members. 55

Examples of 3 to 7 membered saturated heterocyclic radicals comprise 1- or 2-aziridinyl, 1-, 2- or 3-azetidinyl, 1-, 2- or 3-pyrrolidinyl, 1-, 2-, 3- or 4-piperidinyl , 1-, 2- or 3-morpholinyl, 1-, 2- or 3-thiomorpholinyl, 1-, 2- or 3-piperazinyl, 1-, 2- or 4-oxazolidinyl, 1-, 3- or 4-isoxazolidinyl , 2-oxyranyl, 2- or 3-oxetanyl, 2- or 3-oxolanyl, 2-, 3- or 4-oxanyl, 1,3-dioxolan-2- or

4-yl and the like, which may be unsubstituted or may carry 1, 2 or 3 of the aforementioned radicals Ra and / or Rb.

Unsaturated non-aromatic heterocyclic radicals are heterocyclic radicals which generally have 5-, 6- or 7 ring-forming atoms and have 1 or 2 double bonds that do not form an aromatic system of electrons p. Examples are 2,3-dihydropyrrolyl, 3,4-dihydropyrrolyl, 2,3-dihydrofuranyl, 3,4-dihydrofuranyl, 2,3-dihydrothiophenyl, 3,4-5 dihydrothiophenyl, 1,2-dihydropyridinyl, 2,3-Dihydropyridinyl , 3,4-dihydropyridinyl, 1,2,3,4-tetrahydropyridinyl, 2,3,4,5-tetrahydropyridinyl,

and the like

The 5 or 6 membered heteroaromatic radicals are heteroaromatic cyclic radicals, where the cyclic radical has 5 or 6 atoms which form the ring (ring members) and where 1, 2, 3 or 4 atoms 10 ring members are generally selected from O, S and N, the other ring member atoms being carbon atoms. More precisely, heteroaromatic radicals comprise a heteroatom selected from O, S and N as a ring member and optionally 1, 2 or 3 additional N atoms as ring members. Heteroaromatic radicals can be linked through a carbon atom (C bond) or a nitrogen atom (N bond). Preferred heteroaromatic radicals comprise a nitrogen atom as a ring member atom and optionally 1, 2 or 3 additional heteroatoms as ring members, which are independently selected from one another of O, S and N. As an obvious matter, only one of the additional ring member heteroatoms may be O or S and only 5-member heteroaromatic radicals may comprise O or S as ring members. Probably preferred heteroaromatic radicals comprise a heteroatom as a ring member, which is selected from O, S and N, and optionally 1, 2 or 3 additional nitrogen atoms as ring members. Examples of 5 or 6 membered heteroaromatic radicals comprise 2-, 3-, or 4-pyridyl, 2-, 4- or 5-pyrimidinyl, pyrazinyl, 3- or 4-pyridazinyl, 2- or 3-thienyl, 2- or 3-furyl, 1-, 2- or 3-pyrrolyl, 1-, 2- or 4-imidazolyl, 1-, 3- or 4-pyrazolyl, 1- or 3- [1,2,4] -triazolyl, 1- or 4- [1,2,3] -triazolyl, 1-, 2- or 5-tetrazolyl, 2-, 3- or 5-oxazolyl, 3-, 4- or 5-isoxazolyl, 2-, 3- or 5-thiazolyl, 3-, 4- or 5-isothiazolyl, 4- or 5- [1,2,3] -oxadiazolyl, [1,2,5] -oxadiazolyl (= furazanil), 3- or 5- [ 1,2,4] -oxadizolyl, [1,3,4] -oxadizolyl, 4- or 5- [1,2,3] -thiadiazolyl, [1,2,5] -thiadiazolyl, 3- or 5- [ 1,2,4] -thiadiazolyl or [1,3,4] -thiadiazolyl, which may be unsubstituted or may carry one of the aforementioned radicals Ra and optionally 1 or 2 of the aforementioned radicals Rb.

An experienced person will appreciate that the radical R9 may be linked to any of the carbon atoms of the pyridine or pyrimidine structural unit of the formula I, thus replacing a hydrogen atom. Preferably, R9 is linked in position 2 with respect to position 1 of the nitrogen ring atom and position 3 of group 30 NR3-SO2-Ar.

Preferably, Ar is phenyl or a 5- or 6-membered heteroaromatic aromatic radical linked by C, which comprises a nitrogen atom as a ring member and an additional 0, 1, 2 or 3 heteroatoms, independently of each other, selected from O, S and N, as ring members which may be unsubstituted or may carry 1, 2 or 3 of the aforementioned radicals Ra and / or Rb. Among these heteroaromatic radicals, those comprising 1, 2 or 3 nitrogen atoms and no additional heteroatom as a ring member, or 1 or 2 nitrogen atoms and 1 atom, selected from O and S, are preferred as ring members. However, thienyl and furyl are similarly preferred. Preferred heteroaromatic radicals Ar are 2- or 3-thienyl, 2-, 3- or 4-pyridyl, 2-, 4- or 5-pyrimidinyl, 2-, 3- or 5-thiazolyl, 1,2,4-triazol- 3-yl, 1,2,3-triazol-4-yl, 1,3,4-thiadiazol-2-yl, in particular 2-thienyl, 2-pyrimidinyl, 5-pyrimidinyl and 2-pyridinyl which may not be substituted or may carry one of the aforementioned radicals Ra and optionally 1 or 2 of the aforementioned radicals Rb. More preferably, Ar is phenyl which can carry one of the aforementioned radicals Ra and optionally 1 or 2 of the aforementioned radicals Rb.

A person skilled in the art will appreciate that the radical R9 may be linked to any of the carbon atoms of the pyridine or pyrimidine structural unit in formula I, substituting a hydrogen atom as a consequence. Preferably, R9 is linked in position 2 with respect to position 1 of the nitrogen atom 45 of the ring and position 3 of the group NR3-SO2-Ar.

Preferably, Ar is phenyl or a 5- or 6-membered heteroaromatic aromatic radical linked by C, which comprises a nitrogen atom as a ring member and an additional 0, 1, 2 or 3 heteroatoms, independently of each other, selected from O , S and N, as ring members which may be unsubstituted or may carry 1, 2 or 3 of the aforementioned radicals Ra and / or Rb. Among these heteroaromatic radicals, those that comprise 1, 2 or 3 nitrogen atoms and no additional heteroatom as a ring member, or 1 or 2 nitrogen atoms and 1 atom, selected from O and S, are preferred as ring members. However, thienyl and furyl are similarly preferred. Preferred heteroaromatic radicals Ar are 2- or 3-thienyl, 2-, 3- or 4-pyridyl, 2-, 4- or 5-pyrimidinyl, 2-, 3- or 5-thiazolyl, 1,2,4-triazol- 3-yl, 1,2,3-triazol-4-yl, 1,3,4-thiadiazol-2-yl, in particular 2-thienyl, 2-pyrimidinyl, 5-pyrimidinyl and 2-pyridinyl which may not be substituted or may carry one of the aforementioned radicals Ra and optionally 1 or 2 of the aforementioned radicals Rb. More preferably, Ar is phenyl which can carry one of the aforementioned radicals Ra and optionally 1 or 2 of the aforementioned radicals Rb.

Preferably, the aromatic radical Ar carries a radical Ra and optionally one or two additional radicals Rb as mentioned above, Rb being particularly selected from methyl, fluorinated methyl, halogen, more preferably from fluorine or chlorine.

The aforementioned 5 heteroaromatic Ar radicals preferably carry a Ra radical at position 3 (with respect to the position of the SO2- radical) and optionally one or two additional radicals Rb, which 5 are preferably selected from halogen , in particular fluorine or chlorine.

Phenyl and the 6-member heteroaromatic radicals mentioned above preferably carry a radical Ra at position 4 (with respect to the position of the SO2- radical) and optionally one or two additional radicals Rb, which are preferably selected from halogen, in particular fluorine or chlorine.

In a very preferred embodiment of the invention, Ar is a phenyl bearing a radical Ra at position 4 of the phenyl ring 10 and optionally 1 or 2 additional radicals Rb, which are preferably selected from halogen, in particular from fluorine or chlorine.

In another preferred embodiment of the invention Ar is 2-pyrimidinyl which carries a Ra radical at the 5-position of the pyrimidine ring and optionally 1 or 2 additional radicals Rb, which are preferably selected from halogen, in particular from fluorine or chlorine . fifteen

In a further preferred embodiment of the invention, Ar is 5-pyrimidinyl which carries a Ra radical at position 2 of the pyrimidine ring and optionally 1 or 2 additional radicals Rb, which are preferably selected from halogen, in particular from fluorine or chlorine.

In a further preferred embodiment of the invention Ar is 2-thienyl bearing a radical Ra at the 3 position of the thiophene ring and optionally 1 or 2 additional radicals Rb, which are preferably selected from halogen, 20 in particular from fluorine or chlorine

In a preferred embodiment Ar carrier 1 radical Ra which is selected from the group consisting of C1-C6 alkyl, fluorinated C1-C6 alkyl, C3-C6 cycloalkyl, fluorinated C3-C6 cycloalkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy, NR4R5, 1-aziridinyl, azetidin-1-yl, pyrrolidin-1-yl, piperidin-1-yl, where the last four radicals may be fluorinated, a phenyl group and a 5- or 6-membered C-linked heteroaromatic radical comprising a nitrogen atom as a member of 25 ring and 0, 1, 2 or 3 additional heteroatoms, independently of each other, selected from O, S and N, where the last two mentioned radicals can carry 1, 2, 3 or 4 selected radicals among halogen, C1-C6 alkyl, fluorinated C1-C6 alkyl, C3-C6 cycloalkyl, fluorinated C3-C6 cycloalkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy and NR4R5; and where Ar can carry 1 or 2 additional radicals Rb, which are, independently of one another, selected from halogen, cyano, methyl, fluoromethyl, difluoromethyl, trifluoromethyl, difluoromethoxy and trifluoromethoxy. In this embodiment R4, R5 are, independently of each other, preferably selected from H, C1-C2-alkyl and fluorinated C1-C2-alkyl. Preferably one of the radicals R4 or R5 is different from hydrogen. One of the radicals R4 or R5 may also be C1-C2-alkoxy.

In a very preferred embodiment, the radical Ar preferably carries a radical Ra, which has the formula Ra

 35

where

Y is N, CH or CF,

Ra1 and Ra2 are independently from each other selected from C1-C2-alkyl, C1-C2-alkoxy, fluorinated C1-C2 alkyl, assuming that when Y is CH or CF one of the radicals Ra1 or Ra2 may also be hydrogen or fluorine, or

Ra1 and Ra2 together form a radical (CH2) k where 1 or 2 of the hydrogen atoms can be replaced by fluorine, hydroxy, oxo, C1-C2-alkyl or C1-C2-alkoxy, where a CH2 structural unit can be replaced by O, S, S = O, SO2 or N-Rc, Rc, when they are hydrogen or C1-C2-alkyl and where k is 2, 3, 4, 5 or 6;

In particular

Ra1 or Ra2 are independently from each other selected from C1-C2-alkyl, fluorinated C1-C2 alkyl, in particular fluoromethyl, difluoromethyl or trifluoromethyl, assuming that when Y is CH or CF one of the radicals Ra1 or Ra2 may also be hydrogen or fluorine, or

Ra1 and Ra2 form a radical (CH2) k where 1 or 2 of the hydrogen atoms can be replaced by fluorine and where k is 2, 3 or 4, in particular CH2-CH2, CHF-CH2 CF2-CH2, CH2-CH2 -CH2, CHF-CH2-CH2, CF2-CH2-CH2, CH2-CHF-5 CH2, CH2-CF2-CH2.

In the case that Ra1 and Ra2 are different from each other, the radical of the aforementioned formula Ra ’may have a good configuration (R) - or (S) with respect to the structural unit Y.

Examples for preferred radicals Ra 'comprise isopropyl, (R) -1-fluoroethyl, (S) -1-fluoroethyl, 2-fluoroethyl, 1,1-difluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, ( R) -1-fluoropropyl, (S) -1-fluoropropyl, 2-fluoropropyl, 3-fluoropropyl, 1,1-difluoropropyl, 2,2-difluoropropyl, 3,3-difluoropropyl, 3,3,3-trifluoropropyl, (R) -2-fluoro-1-methyl ethyl, (S) -2-fluoro-1-methyl ethyl, (R) -2,2-difluoro-1-methyl ethyl, (S) -2,2-difluoro-1- methylethyl, (R) -1,2-difluoro-1-methylethyl, (S) -1,2-difluoro-1-methylethyl, (R) -2,2,2-trifluoro-1-methyl ethyl, (S) - 2,2,2-trifluoro-1-methylethyl, 2-fluoro-1- (fluoromethyl) ethyl, 1- (difluoromethyl) -2,2-difluoroethyl cyclopropyl, cyclobutyl, 1-fluorocyclopropyl, and 2-fluorocyclopropyl.

Ra 'radicals are also preferred where one of Ra1 or Ra2 is C1-C2-alkoxy and the other of Ra1 or Ra2 is selected from H, C1-15 C2-alkyl, in particular methyl, fluorinated C1-C2 alkyl, in particular fluoromethyl , difluoromethyl or trifluoromethyl. As examples there may be mentioned N-methoxy-N-methylamino, N-methoxyamino and N-ethoxyamino.

Preferred radicals of the formula Ra 'also comprise those where Y is nitrogen and where Ra1 and Ra2 form a radical (CH2) t where 1 or 2 of the hydrogen atoms can be replaced by fluorine, methyl, trifluoromethyl, methoxy or oxo and where t is 2, 3, 4 or 5. Examples of azetidin-1-yl, 2-methylazetidin-1-yl, (S) -2-methylazetidin-1-20 yl, (R) -2-methylazetidine- 1-yl, 3-fluoroazetidin-1-yl, 3-methoxyazetidin-1-yl, 3-hydroxyazetidin-1-yl, 1,3-oxazol-5-yl, pyrrolidin-1-yl, (S) -2- fluoropyrrolidin-1-yl, (R) -2-fluoropyrrolidin-1-yl, 3-fluoropyrrolidin-1-yl, (S) -3-fluoropyrrolidin-1-yl, (R) -3-fluoropyrrolidin-1-yl, 2,2-Difluoropyrrolidin-1-yl, 3,3-difluoropyrrolidin-1-yl, 2-methylpyrrolidin-1-yl, (S) -2-methylpyrrolidin-1-yl, (R) -2-methylpyrrolidin-1- yl, 3-methylpyrrolidin-1-yl, (S) -3-methylpyrrolidin-1-yl, (R) -3-methylpyrrolidin-1-yl, 2,2-dimethylpyrrolidin-1-yl, 3,3-dimethylpyrrolidin- 1-yl, 2-trifluoromethylpyrrolidin-1-yl, (S) -2-trifluoromethylpyrr olidin-1-yl, (R) -2-25 trifluoromethylpyrrolidin-1-yl, 3-trifluoromethylpyrrolidin-1-yl, (S) -3-trifluoromethylpyrrolidin-1-yl, (R) -3-trifluoromethylpyrrolidin-1-yl , 2-oxopyrrolidin-1-yl, piperidin-1-yl, 2-methylpiperidin-1-yl, (S) -2-methylpiperidin-1-yl and (R) -2-methylpiperidin-1-yl.

In the same way, radicals Ra 'are preferred, where Ra1 and Ra2 together form a radical (CH2) or where 1 or 2 of the hydrogen atoms can be replaced by fluorine, hydroxy, oxo, C1-C2-alkyl or C1-C2 -alkoxy, where a CH2 structural unit is replaced by O, S, S = O, SO2 or N-Rc, Rc, when they are hydrogen or C1-C2-alkyl and where u is 2, 3, 30 4, 5 or 6 Examples for preferred radicals of the formula Ra 'also comprise 4-morpholinyl, 4-thiomorpholinyl, 4- (1,1-dioxo) thiomorpholinyl, piperazin-1-yl, 4-methylpiperazin-1-yl, 2-oxo-oxazolidin -3-yl, pyrrolidin-2-yl, (S) -pyrrolidin-2-yl, (R) -pyrrolidin-2-yl, pyrrolidin-3-yl, (S) -pyrrolidin-3-yl, (R) -pyrrolidin-3-yl, 2-fluoropyrrolidin-1-yl, 1-methylpyrrolidin-2-yl, (S) -1-methylpyrrolidin-2-yl, (R) -1-methylpyrrolidin-2-yl, 1-methylpyrrolidin -3-yl, (S) -1-methylpyrrolidin-3-yl and (R) -1-methylpyrrolidin-3-yl.

Among the radicals of the formula Ra ’are preferred those that carry 1, 2, 3 or 4, in particular 1, 2 or 3 fluorine atoms. 35

In a further preferred embodiment, Ar carries a Ra radical, which is selected from 5 or 6 membered heteroaromatic radicals having as heteroatom ring members 1 selected from O, S and N and which may additionally have 1, 2 or 3 atoms of nitrogen as ring members, and where the 5- or 6-membered heteroaromatic radical may carry 1, 2 or 3 substituents selected from halogen, NO2, NH2, OH, CN, C1-C6 alkyl, C3-C6 cycloalkyl, C1- alkoxy C6, fluorinated C1-C6 alkyl, fluorinated C3-C6 cycloalkyl, fluorinated C1-C6 alkoxy, Hydroxyalkyl C1-C6, C1-C4-40 alkoxy-C2-C4-alkyl, Hydroxyalkoxy C1-C6, C1-C4-alkoxy-C2 -C4-alkoxy, C1-C6 alkylcarbonyl, C1-C6amino alkyl, di-C1-C6amino alkyl, C1-C6 alkylaminocarbonyl, di-C1-C6 alkylaminocarbonyl, C1-C6 alkyl fluorinated carbonyl, C1-C6 alkylcarbonylamino, C1- alkyl C6 fluorinated amino carbonyl, C1-C6 alkylcarbonyloxy, C1-C6 alkyl fluorinated carbonyloxy, C1-C6 alkoxycarbonyl, C1- Alkylthio C6, fluorinated C1-C6 alkylthio, C1-C6 alkyl sulfinyl, C1-C6 alkyl sulfonyl, C1-C6 alkyl fluorinated sulfinyl and C1-C6 alkyl fluorinated sulfonyl. Among these Ra radicals, preference is given to radicals selected from 2-, 3-, or 4-pyridyl, 2-, 4- or 5-pyrimidinyl, pyrazinyl, 3- or 4-pyridazinyl, 2- or 3-thienyl, 2- or 3-furyl, 1-, 2- or 3-pyrrolyl, 1-, 2-, 4- or 5-imidazolyl, 1-, 3-, 4- or 5-pyrazolyl, 1-, 3- or 5 - [1,2,4] -triazolyl, 1-, 4- or 5- [1,2,3] -triazolyl, 1- or 5- (1H) -tetrazolyl, 2- or 5- (2H) -tetrazolyl , 2-, 4- or 5-oxazolyl, 3-, 4- or 5-isoxazolyl, 2-, 4- or 5-thiazolyl, 3-, 4- or 5-isothiazolyl, 4- or 5- [1,2 , 3] -oxadiazolyl, 3- or 4- [1,2,5] -oxadiazolyl (= furazanil), 3- or 5- [1,2,4] -oxadiazolyl, 2- or 5- [1,3, 4] -oxadizolyl, 4- or 5- [1,2,3] -thiadiazolyl, 3- or 4- [1,2,5] -thiadiazolyl, 3- or 5- [1,2,4] -thiadizolyl or 2- or 5- [1,3,4] -thiadiazolyl, in particular from 50 of 2- or 3-furanyl, 2- or 3-thienyl, 1-, 2- or 3-pyrrolyl, 1-, 3- , 4- or 5-pyrazolyl, 1-, 2-, 4- or 5-imidazolyl, 2-, 4- or 5-oxazolyl, 3-, 4-or 5-isoxazolyl, 2 or 5- [1,3, 4] -thiadiazolyl, 1-, 3- or 5- [1, 2,4] -triazolyl, 1-, 4- or 5- [1,2,3] -triazolyl, 1- or 5- (1 H) -tetrazolyl and 2- or 5- (2H) -tetrazolyl, and specifically from 1-, 3-, 4- or 5-pyrazolyl, in particular 1-pyrazolyl, and 2-, 4- or 5-oxazolyl, in particular 4- or 5-oxazolyl. The heteroaromatic radical may be unsubstituted or may carry 1 to 3 substituents as indicated above. Preferred substituents on the heteroaromatic Ra are selected from halogen, C1-C4-alkyl, C1-C4-alkoxy, fluorinated C1-C4 alkyl and fluorinated C1-C4 alkoxy.

In a further preferred embodiment Ar carrier 1 radical Ra which is selected from the group consisting of (CH2) vCF3, (CH2) vCHF2, (CH2) vCH2F, O (CH2) vCF3, O (CH2) vCHF2, O (CH2) vCH2F , where v is 0, 1, 2 or 3. In this embodiment Ar may also carry 1 or 2 additional radicals Rb, which are, independently of each other, selected from halogen, cyano, methyl, fluoromethyl, difluoromethyl, trifluoromethyl, difluoromethoxy and trifluoromethoxy. Preferably, Ar does not carry an additional radical Rb. In this embodiment, Ar is preferably phenyl which carries 1 radical Ra which 5 is selected from the group consisting of (CH2) vCF3, (CH2) vCHF2, (CH2) vCH2F, O (CH2) vCF3, O (CH2) vCHF2 , O (CH2) vCH2F, where v is 0, 1, 2 or 3. In this embodiment Ar is preferably phenyl, which carries Ra in position 4 with respect to the group SO2.

In another embodiment of the invention, Ar carries 1 radical Ra which is selected from the group consisting of C2-C6 alkenyl, C2-C6 fluorinated alkenyl, C1-C6 hydroxyalkyl, C1-C6-C1-C4 alkoxy, C1- hydroxy alkoxy C6, C1-C4 alkoxy-C1-C6 alkoxy, 10 COOH, CH2NR4R5, ONR4R5, NHC (O) NR4R5, C (O) NR4R5, SO2NR4R5, C1-C6 alkylcarbonyl, fluorinated C2-C6-alkylcarbonyl, C1-C6 alkylcarbonylamino , C1-C6 alkyl fluorinated amino carbonyl, C1-C6 alkyl carbonyloxy, C1-C6 alkyl fluorinated carbonyloxy, C1-C6 alkoxycarbonyl, C1-C6 alkylthio, fluorinated C1-C6 alkyl, C1-C6 alkyl sulfinyl, C1-C6 alkyl sulfonyl , C1-C6 alkyl fluorinated sulfinyl, C1-C6 alkyl fluorinated sulfonyl, phenylsulfonyl, phenoxy, benzyloxy, pyridine-2-yloxy, and a 5 or 6 membered heteroaromatic radical linked through N, where the last six mentioned radicals can be mentioned carry 1, 2, 3 or 4 radicals selected from halogen, NO2, NH2, OH, CN, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 alkoxy, alkyl or C1-C6 fluorinated, C3-C6 cycloalkyl fluorinated, C1-C6 alkoxy fluorinated, Hydroxyalkyl C1-C6, C1-C4-alkoxy-C2-C4-alkyl, Hydroxyalkoxy C1-C6, C1-C4-alkoxy-C2-C4- alkoxy, C1-C6 alkylcarbonyl, C1-C6amino alkyl, di-C1-C6amino alkyl, C1-C6 alkylaminocarbonyl, di-C1-C6 alkylaminocarbonyl, C1-C6 alkyl fluorinated carbonyl, C1-C6 alkylcarbonylamino, C1-C6 alkylcarbonyl amino fluorinated, C1-C6 alkyl carbonyloxy, C1-C6 alkyl 20 carbonyloxy fluorinated, C1-C6 alkoxycarbonyl, C1-C6 alkyl, fluorinated C1-C6 alkyl, C1-C6 alkyl sulfinyl, C1-C6 alkyl sulfonyl, C1-C6 alkyl sulfinyl fluorinated and fluorinated C1-C6 alkyl sulfonyl.

In another embodiment of the invention, Ar is phenyl, which carries 1 Ra radical and at least one Rb radical and where Ra and a Rb radical are linked to two adjacent carbon atoms of the phenyl and form a heterocyclic or carbocyclic ring of 5 or 6 members which is fused to the phenyl ring and which is unsubstituted or can carry 1, 2 or 3 radicals as indicated above. Examples of a phenyl ring fused to a heterocyclic or carbocyclic ring, saturated or unsaturated 5 or 6 membered comprise indenyl, indanyl, naphthyl, tetralin, benzofuranyl, 2,3-dihydrobenzofuranyl, benzothienyl, indolyl, indazolyl, benzimidazolyl, benzoxatiazolilo, benzoxadiazolyl, benzothiadiazolyl , benzoxazinyl, dihydrobenzoxazinyl, cholinolinyl, isoquinolinyl, tetrahydroisoquinolinyl, chromenyl, chromanyl and the like, which may be unsubstituted or may carry 1, 2 or 3 of the aforementioned radicals. Preferred substituents for the saturated or unsaturated 5 or 6 membered heterocyclic or carbocyclic ring fused to the phenyl ring are selected from halogen, C1-C4-alkyl, C1-C4-alkoxy, fluorinated C1-C4 alkyl and fluorinated C1-C4 alkoxy.

Specifically, Ra is selected from C1-C4-alkyl, fluorinated C1-C4 alkyl, in particular (CH2) vCF3, (CH2) vCHF2 and (CH2) vCH2F, C1-C4-alkoxy and fluorinated C1-C4 alkoxy, in particular O (CH2) vCF3, O (CH2) vCHF2 and O (CH2) vCH2F.

Alternatively, Ra is specifically selected from a 5 or 6 membered heteroaromatic radical having 35 as heteroatom 1 ring members selected from O, S and N and which may additionally have 1, 2 or 3 nitrogen atoms as ring members, and where the 5- or 6-membered heteroaromatic radical may be substituted as described above. Preferred heteroaromatic radicals of 5 or 6 Ra members and preferred substituents thereof are as described above.

More specifically, Ar is phenyl which preferably carries at position 4 with respect to position 1 of the sulfonyl group, a radical Ra which is selected from C1-C4-alkyl, fluorinated C1-C4 alkyl, in particular (CH2) vCF3, (CH2) vCHF2 and (CH2) vCH2F, C1-C4-alkoxy, fluorinated C1-C4 alkoxy, in particular O (CH2) vCF3, O (CH2) vCHF2 and O (CH2) vCH2F, and a radical 5 or 6 member heteroaromatic as described above.

The radical R1 is preferably H, C1-C4-alkyl, C3-C4-cycloalkyl, C3-C4-cycloalkylmethyl, C3-C4-alkenyl, fluorinated C2-C4 alkyl, fluorinated C3-C4 cycloalkyl, fluorinated C3-C4 cycloalkyl methyl , fluorinated C3-C4 alkenyl, formyl or C1-C3-45 alkylcarbonyl, in particular H, C1-C4-alkyl, C3-C4-alkenyl, fluorinated C2-C4 alkyl, fluorinated C3-C4 alkenyl, more preferably H, methyl, ethyl, n-propyl, fluorinated C2-C3 alkyl or 1-propen-3-yl (allyl), specifically H, methyl or n-propyl, in particular n-propyl.

A preferred embodiment of the invention relates to compounds, where R 1a is Hydrogen. In these compounds R 1 has the meaning given above and is preferably different from hydrogen. In particular R 1 is N-propyl. In 50 this embodiment R2a is preferably hydrogen while R2 is preferably hydrogen, methyl or fluorinated methyl. In particular, both R2a and R2 are hydrogen or one of the radicals R2a and R2 is Hydrogen while the other is methyl. In this embodiment both R8a and R8 are preferably hydrogen

In a further preferred embodiment, R1a is different from hydrogen and is preferably C1-C4-alkyl, C3-C4-alkenyl, fluorinated C2-C4 alkyl, fluorinated C3-C4 alkenyl, more preferably methyl, n-propyl, C2 alkyl -C3 fluorinated or 55 1-propen-3-yl, in particular n-propyl. In these compounds R1 has the meaning given above. In particular R1 is H, methyl or n-propyl. In this embodiment, R1 and R1a have the same meaning and are in particular both methyl or both n-propyl. In this embodiment R2a is preferably hydrogen while R2 is preferably hydrogen, methyl

or fluorinated methyl. In particular both R2a and R2 are hydrogen or one of the radicals R2a and R2 is Hydrogen while the other is methyl. In this embodiment both R8a and R8 are preferably hydrogen.

In a further preferred embodiment, R2a and R1a together are (CR6R7) n being n 2, 3 or 4 and specifically 3. R6 and R7 are preferably H. R2 is preferably hydrogen In these compounds R1 has the meaning given more above. In particular R1 is H, n-propyl, 1-propen-3-yl. In this embodiment both R8a and R8 are preferably hydrogen. 5

In a further preferred embodiment, R8a and R1a together are (CR6R7) s being 2 or 3 and specifically 2. R6 and R7 are preferably H. R2 and R2a are preferably H. R8 is preferably hydrogen In these Compounds, R1 has the meaning given above. In particular, R1 is H, n-propyl, 1-propen-3-yl and specifically H or n-propyl.

In a further preferred embodiment, R1 and R1a together are (CR6R7) r being r 3, 4 or 5 and specifically 4. R6 and R7 are preferably H. In this embodiment both R2a and R2 as well as both R8a and R8 are of preferable form hydrogen. 10

A preferred embodiment of the invention relates to compounds of the formula I, where X is CH.

Another preferred embodiment of the invention relates to compounds of the formula I, where X is N.

Preferably, R3 is H or methyl and more preferably H.

A preferred embodiment of the invention relates to compounds of the formula I, wherein R9 is selected from C1-C4-alkyl, in particular methyl, C1-C4-alkoxy, in particular methoxy, and hydrogen. fifteen

In a further preferred embodiment, R9 is linked together with the ring nitrogen of the pyridine and pyrimidine structural unit, and R9 is preferably C1-C4-alkoxy, in particular methoxy.

In a further preferred embodiment R9 is linked together with the ring nitrogen of the structural unit pyridine and pyrimidine respectively, and R9 is preferably C1-C4-alkyl, in particular methyl.

Another preferred embodiment relates to compounds where X is CH, and R1a, R2, R2a, R8 and R8a are H, R9 is methoxy and 20 Ra and Ar are as defined above.

Another preferred embodiment relates to compounds where X is N, R1a, R2, R2a, R8 and R8a are H, R9 is methoxy and Ra and Ar are as defined above.

In a preferred embodiment, Ar (together with Ra) has one of the meanings given in Table B below.

Preferred embodiments of the invention are compounds of the following formulas Ia, Ib, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, Il, 25 Im, In, Io, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, Ix, Iy, and Iz and the physiologically tolerated acid addition salts thereof. With respect to the carbon atom carrying four different groups, the compounds of the formula Ii, Ij, Ik Il, Im, In, Io, Ip, Iq, Ir, es and It may exist as R enantiomers or S enantiomers as well as mixtures of enantiomers such as racemic mixtures. Preferred embodiments include the S and R enantiomers of Ii, Ij, Ik, Il, Im, In, Io, Ip, Iq, Ir, Is, and It and mixtures of the enantiomers. 30

In the compounds of the formulas Ia, Ib, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, Il, Im, In, Io, Ip, Iq, Ir, Is, It, R1, Ar and R1a are as defined above with particular preference given to compounds where R1, Ar and R1a have one of the preferred meanings.

In the compounds of the formulas Ib, Iw, Ix, Iy and Iz, Ar is as defined above giving particular preference to those compounds where Ar has one of the preferred meanings.

Examples of preferred compounds of formula I are given in the following tables A-1, A-2, A-3, A-4, A-5, A-6, A-7, A-8, A-9 , A-10, A-11, A-12, A-13, A-14, A-15, A-16, A-17, A-18, A-19, A-20, B-1, B -2, B-3, B-4, B-5, and B-6.

Table A-1: Compounds of the formula Ia, where R1a is H and Ar and R1 have the meaning given in one of the rows of table A. 5

Table A-2: Compounds of the formula Ib, where R1a is H and Ar and R1 have the meaning given in one of the rows of table A.

Table A-3: Compounds of the formula Ic, where R1a is H and Ar and R1 have the meaning given in one of the rows of table A.

Table A-4: Compounds of the formula Id, where R1a is H and Ar and R1 have the meaning given in one of the rows of table A.

Table A-5: Compounds of the formula Ie, where R1a is H and Ar and R1 have the meaning given in one of the rows of table A.

Table A-6: Compounds of the formula If, where R1a is H and Ar and R1 have the meaning given in one of the rows of table A. 15

Table A-7: Compounds of the formula Ig, where Ar and R1 have the meaning given in one of the rows of table A.

Table A-8: Compounds of the formula Ih, where Ar and R1 have the meaning given in one of the rows of table A.

Table A-9: Compounds of formula Ii, including pure S isomers, pure R isomers and racemic mixtures, where Ar and R1 have the meaning given in one of the rows of table A.

Table A-10: Compounds of the formula Ij, including pure S isomers, pure R isomers and racemic mixtures, where Ar and R1 have the meaning given in one of the rows of table A.

Table A-11: Compounds of the formula Ik, including pure S isomers, pure R isomers and racemic mixtures, where Ar and R1 have the meaning given in one of the rows of table A.

Table A-12: Compounds of the formula Il, including pure S isomers, pure R isomers and racemic mixtures, where Ar and R1 have the meaning given in one of the rows of table A.

Table A-13: Compounds of the formula Im, including pure S isomers, pure R isomers and racemic mixtures, where Ar and R1 have the meaning given in one of the rows of table A.

Table A-14: Compounds of the formula In, including pure S isomers, pure R isomers and racemic mixtures, where Ar and R1 have the meaning given in one of the rows of table A.

Table A-15: Compounds of the formula Io, including pure S isomers, pure R isomers and racemic mixtures, where Ar and R1 have the meaning given in one of the rows of table A. 10

Table A-16: Compounds of the formula Ip, including pure S isomers, pure R isomers and racemic mixtures, where Ar and R1 have the meaning given in one of the rows of table A.

Table A-17: Compounds of the formula Iq, including pure S isomers, pure R isomers and racemic mixtures, where Ar and R1 have the meaning given in one of the rows of table A.

Table A-18: Compounds of the formula Ir, including pure S isomers, pure R isomers and racemic mixtures, where Ar and R1 have the meaning given in one of the rows of Table A.

Table A-19: Compounds of the formula Is, including pure S isomers, pure R isomers and racemic mixtures, where Ar and R1 have the meaning given in one of the rows of table A.

Table A-20: Compounds of the formula It, including pure S isomers, pure R isomers and racemic mixtures, where Ar and R1 have the meaning given in one of the rows of table A. 20

Table A

 Do not.

 R1 Ar

 one.

 methyl 4- (trifluoromethoxy) -phenyl

 2.

 methyl 3- (trifluoromethoxy) -phenyl

 3.

 methyl 4-cyanophenyl

 Four.

 methyl 4-methylphenyl

 5.

 methyl 4-ethylphenyl

 6.

 methyl 4-propylphenyl

 7.

 methyl 4-methoxyphenyl

 8.

 methyl 4-fluorophenyl

 9.

 methyl 4-chlorophenyl

 10.

 methyl 4-bromophenyl

 eleven.

 methyl 3- (trifluoromethyl) phenyl

 12.

 methyl 4- (trifluoromethyl) phenyl

 Do not.

 R1 Ar

 13.

 methyl 2- (trifluoromethyl) phenyl

 14.

 methyl 3,4-difluorophenyl

 fifteen.

 methyl 4-bromo-3-fluorophenyl

 16.

 methyl 4-bromo-2-fluorophenyl

 17.

 methyl 4-bromo-2,5-difluorophenyl

 18.

 methyl 2-fluoro-4-isopropylphenyl

 19.

 methyl 4-hydroxyphenyl

 twenty.

 methyl 4-isopropylphenyl

 twenty-one.

 methyl 4-sec-butylphenyl

 22

 methyl 4-isobutylphenyl

 2. 3.

 methyl 4- (1,1-dimethylpropyl) -phenyl

 24.

 methyl 4-vinylphenyl

 25.

 methyl 4-isopropenylphenyl

 26.

 methyl 4- (fluoromethyl) phenyl

 27.

 methyl 3- (fluoromethyl) phenyl

 28.

 methyl 2- (fluoromethyl) phenyl

 29.

 methyl 4- (difluoromethyl) phenyl

 30

 methyl 3- (difluoromethyl) phenyl

 31.

 methyl 2- (difluoromethyl) phenyl

 32

 methyl 4- (1-fluoroethyl) -phenyl

 33.

 methyl 4 - ((S) -1-fluoroethyl) -phenyl

 3. 4.

 methyl 4 - ((R) -1-fluoroethyl) -phenyl

 35

 methyl 4- (2-fluoroethyl) -phenyl

 36.

 methyl 4- (1,1-difluoroethyl) -phenyl

 37.

 methyl 4- (2,2-difluoroethyl) -phenyl

 38.

 methyl 4- (2,2,2-trifluoroethyl) -phenyl

 39.

 methyl 4- (3-fluoropropyl) -phenyl

 40

 methyl 4- (2-fluoropropyl) -phenyl

 41.

 methyl 4 - ((S) -2-fluoropropyl) -phenyl

 Do not.

 R1 Ar

 42

 methyl 4 - ((R) -2-fluoropropyl) -phenyl

 43

 methyl 4- (3,3-difluoropropyl) -phenyl

 44.

 methyl 4- (3,3,3-trifluoropropyl) -phenyl

 Four. Five.

 methyl 4- (1-fluoro-1-methyl ethyl) -phenyl

 46.

 methyl 4- (2-fluoro-1-methylethyl) -phenyl

 47

 methyl 4 - ((S) -2-fluoro-1-methylethyl) -phenyl

 48.

 methyl 4 - ((R) -2-fluoro-1-methylethyl) -phenyl

 49.

 methyl 4- (2,2-difluoro-1-methylethyl) -phenyl

 fifty.

 methyl 4 - ((S) -2,2-difluoro-1-methylethyl) -phenyl

 51.

 methyl 4 - ((R) -2,2-difluoro-1-methylethyl) -phenyl

 52

 methyl 4- (2,2,2-trifluoro-1-methylethyl) -phenyl

 53.

 methyl 4 - ((S) -2,2,2-trifluoro-1-methylethyl) -phenyl

 54

 methyl 4 - ((R) -2,2,2-trifluoro-1-methylethyl) -phenyl

 55.

 methyl 4- (2-fluoro-1-fluoromethylethyl) -phenyl

 56.

 methyl 4- (1-difluoromethyl-2,2-difluoroethyl) -phenyl

 57.

 methyl 4- (1,1-dimethyl-2-fluoroethyl) -phenyl

 58.

 methyl 4-ethoxyphenyl

 59.

 methyl 4-propoxyphenyl

 60

 methyl 4-isopropoxyphenyl

 61.

 methyl 4-butoxyphenyl

 62

 methyl 4- (fluoromethoxy) -phenyl

 63.

 methyl 4- (difluoromethoxy) -phenyl

 64.

 methyl 4- (2-fluoroethoxy) -phenyl

 65

 methyl 4- (2,2-difluoroethoxy) -phenyl

 66.

 methyl 4- (2,2,2-trifluoroethoxy) -phenyl

 67.

 methyl 4- (1,1,2,2-tetrafluoroethoxy) -phenyl

 68.

 methyl 4-cyclopropylphenyl

 69.

 methyl 4-cyclobutylphenyl

 70.

 methyl 4-cyclopentylphenyl

 Do not.

 R1 Ar

 71.

 methyl 4- (2,2-difluorocyclopropyl) -phenyl

 72.

 methyl 3-fluoro-4-isopropylphenyl

 73

 methyl 4- (1-hydroxy-1-methylethyl) -phenyl

 74.

 methyl 4- (2-hydroxy-2-methylpropyl) -phenyl

 75.

 methyl 4-acetylphenyl

 76

 methyl 4-carboxyphenyl

 77.

 methyl 4- (O-benzyl) -phenyl

 78.

 methyl 4- (2-methoxyethoxy) -phenyl

 79.

 methyl 4- (CH2-N (CH3) 2) -phenyl

 80.

 methyl 4- (NH-CO-NH2) -phenyl

 81.

 methyl 4- (methylsulfanyl) -phenyl

 82.

 methyl 4- (fluoromethylsulfanyl) phenyl

 83.

 methyl 4- (difluoromethylsulfanyl) -phenyl

 84.

 methyl 4- (trifluoromethylsulfanyl) -phenyl

 85.

 methyl 4- (methylsulfonyl) -phenyl

 86.

 methyl 4- (N-methoxy-N-methyl-amino) -phenyl

 87.

 methyl 4- (methoxyamino) -phenyl

 88.

 methyl 4- (ethoxyamino) -phenyl

 89.

 methyl 4- (N-methylaminooxy) -phenyl

 90.

 methyl 4- (N, N-dimethylaminooxy) -phenyl

 91.

 methyl 4- (azetidin-1-yl) -phenyl

 92.

 methyl 4- (2-methylazetidin-1-yl) -phenyl

 93.

 methyl 4 - ((S) -2-methylazetidin-1-yl) -phenyl

 94.

 methyl 4 - ((R) -2-methylazetidin-1-yl) -phenyl

 95.

 methyl 4- (3-fluoroazetidin-1-yl) -phenyl

 96.

 methyl 4- (3-methoxyazetidin-1-yl) -phenyl

 97.

 methyl 4- (3-hydroxyazetidin-1-yl) -phenyl

 98.

 methyl 4- (pyrrolidin-1-yl) -phenyl

 99.

 methyl 4- (pyrrolidin-2-yl) -phenyl

 Do not.

 R1 Ar

 100

 methyl 4 - ((S) -pyrrolidin-2-yl) -phenyl

 101.

 methyl 4 - ((R) -pyrrolidin-2-yl) -phenyl

 102

 methyl 4- (pyrrolidin-3-yl) -phenyl

 103.

 methyl 4 - ((S) -pyrrolidin-3-yl) -phenyl

 104.

 methyl 4 - ((R) -pyrrolidin-3-yl) -phenyl

 105.

 methyl 4- (2-fluoropyrrolidin-1-yl) -phenyl

 106.

 methyl 4 - ((S) -2-fluoropyrrolidin-1-yl) -phenyl

 107.

 methyl 4 - ((R) -2-fluoropyrrolidin-1-yl) -phenyl

 108.

 methyl 4- (3-fluoropyrrolidin-1-yl) -phenyl

 109.

 methyl 4 - ((S) -3-fluoropyn-olidin-1-yl) -phenyl

 110.

 methyl 4 - ((R) -3-fluoropyrrolidin-1-yl) -phenyl

 111.

 methyl 4- (2,2-difluoropyrrolidin-1-yl) -phenyl

 112

 methyl 4- (3,3-difluoropyrrolidin-1-yl) -phenyl

 113.

 methyl 4- (2-methylpyrrolidin-1-yl) -phenyl

 114

 methyl 4 - ((S) -2-methylpyrrolidin-1-yl) -phenyl

 115

 methyl 4 - ((R) -2-methylpyrrolidin-1-yl) -phenyl

 116.

 methyl 4- (3-methylpyrrolidin-1-yl) -phenyl

 117.

 methyl 4 - ((S) -3-methylpyrrolidin-1-yl) -phenyl

 118.

 methyl 4 - ((R) -3-methylpyrrolidin-1-yl) -phenyl

 119.

 methyl 4- (1-methylpyrrolidin-2-yl) -phenyl

 120.

 methyl 4 - ((S) -1-methylpyrrolidin-2-yl) -phenyl

 121.

 methyl 4 - ((R) -1-methylpyrrolidin-2-yl) -phenyl

 122.

 methyl 4- (1-methylpyrrolidin-3-yl) -phenyl

 123

 methyl 4 - ((S) -1-methylpyrrolidin-3-yl) -phenyl

 124.

 methyl 4 - ((R) -1-methylpyrrolidin-3-yl) -phenyl

 125

 methyl 4- (2,2-dimethylpyrrolidin-1-yl) -phenyl

 126.

 methyl 4- (3,3-dimethylpyrrolidin-1-yl) -phenyl

 Do not.

 R1 Ar

 127.

 methyl 4- (2-trifluoromethylpyrrolidin-1-yl) -phenyl

 128.

 methyl 4 - ((S) -2-trifluoromethylpyrrolidin-1-yl) -phenyl

 129.

 methyl 4 - ((R) -2-trifluoromethylpyrrolidin-1-yl) -phenyl

 130.

 methyl 4- (3-trifluoromethylpyrrolidin-1-yl) -phenyl

 131.

 methyl 4 - ((S) -3-trifluoromethylpyrrolidin-1-yl) -phenyl

 132.

 methyl 4 - ((R) -3-trifluoromethylpyn-olidin-1-yl) -phenyl

 133

 methyl 4- (2-oxopyrrolidin-1-yl) -phenyl

 134

 methyl 4- (2-oxo-oxazolidin-3-yl) -phenyl

 135

 methyl 4- (piperidin-1-yl) -phenyl

 136.

 methyl 4- (2-methylpiperidin-1-yl) -phenyl

 137.

 methyl 4 - ((S) -2-methylpiperidin-1-yl) -phenyl

 138.

 methyl 4 - ((R) -2-methylpiperidin-1-yl) -phenyl

 139.

 methyl 4- (piperazin-1-yl) -phenyl

 140.

 methyl 4- (4-methylpiperazin-1-yl) -phenyl

 141.

 methyl 4- (morpholin-4-yl) -phenyl

 142.

 methyl 4- (thiomorpholin-4-yl) -phenyl

 143.

 methyl 4- (1-oxo-thiomorpholin-4-yl) -phenyl

 144.

 methyl 4- (1,1-dioxo-thiomorpholin-4-yl) -phenyl

 145.

 methyl 4- (pyrrol-1-yl) -phenyl

 146.

 methyl 4- (pyrrol-2-yl) -phenyl

 147.

 methyl 4- (pyrrol-3-yl) -phenyl

 148.

 methyl 4- (1-methylpyrrol-2-yl) -phenyl

 149.

 methyl 4- (1-methylpyrrol-3-yl) -phenyl

 150

 methyl 4- (furan-2-yl) -phenyl

 151.

 methyl 4- (furan-3-yl) -phenyl

 152.

 methyl 4- (thiophene-2-yl) -phenyl

 153.

 methyl 4- (thiophene-3-yl) -phenyl

 154

 methyl 4- (5-propylthien-2-yl) -phenyl

 155.

 methyl 4- (pyrazol-1-yl) -phenyl

 Do not.

 R1 Ar

 156.

 methyl 4- (pyrazol-3-yl) -phenyl

 157.

 methyl 4- (pyrazol-4-yl) -phenyl

 158.

 methyl 4- (1-methyl-1H-pyrazol-4-yl) -phenyl

 159.

 methyl 4- (1-ethyl-1H-pyrazol-4-yl) -phenyl

 160

 methyl 4- (1-methyl-1H-pyrazol-5-yl) -phenyl

 161.

 methyl 4- (1H-imidazol-2-yl) -phenyl

 162.

 methyl 4- (imidazol-1-yl) -phenyl

 163.

 methyl 4- (1-methylimidazol-2-yl) -phenyl

 164.

 methyl 4- (oxazol-2-yl) -phenyl

 165.

 methyl 4- (oxazol-4-yl) -phenyl

 166.

 methyl 4- (oxazol-5-yl) -phenyl

 167.

 methyl 4- (isoxazol-3-yl) -phenyl

 168.

 methyl 4- (isoxazol-4-yl) -phenyl

 169.

 methyl 4- (isoxazol-5-yl) -phenyl

 170.

 methyl 4 - ([1,2,3] -triazol-1-yl) -phenyl

 171.

 methyl 4 - ([1,2,4] -triazol-1-yl) -phenyl

 172.

 methyl 4 - ([1,2,3] -triazol-2-yl) -phenyl

 173.

 methyl 4- (4H- [1,2,4] -triazol-3-yl) -phenyl

 174.

 methyl 4 - ([1,2,4] -triazol-4-yl) -phenyl

 175.

 methyl 4- (2H- [1,2,3] -triazol-4-yl) -phenyl

 176.

 methyl 4- (4-methyl-4H- [1,2,4] -triazol-3-yl) -phenyl

 177.

 methyl 4- (2-methyl-2H- [1,2,3] -triazol-4-yl) -phenyl

 178.

 methyl 4 - ([1,3,4] -oxadiazol-2-yl) -phenyl

 179.

 methyl 4 - ([1,2,4] -oxadiazol-3-yl) -phenyl

 180

 methyl 4 - ([1,2,4] -oxadiazol-5-yl) -phenyl

 181

 methyl 4 - ([1,2,3] -oxadiazol-4-yl) -phenyl

 182.

 methyl 4 - ([1,2,3] -oxadiazol-5-yl) -phenyl

 183

 methyl 4 - ([1,2,3] -thiadiazol-4-yl) -phenyl

 184

 methyl 4- (1H-tetrazol-5-yl) -phenyl

 Do not.

 R1 Ar

 185.

 methyl 4- (tetrazol-1-yl) -phenyl

 186.

 methyl 4- (2-methyl-2H-tetrazol-5-yl) -phenyl

 187

 methyl 4- (1-methyl-1H-tetrazol-5-yl) -phenyl

 188.

 methyl 4-furazan-3-yl-phenyl

 189.

 methyl 4- (pyrid-2-yl) -phenyl

 190.

 methyl 4- (pyrid-3-yl) -phenyl

 191

 methyl 4- (pyrid-4-yl) -phenyl

 192.

 methyl 4- (pyrimidin-2-yl) -phenyl

 193

 methyl 4- (pyrimidin-4-yl) -phenyl

 194

 methyl 4- (pyrimidin-5-yl) -phenyl

 195.

 methyl 5-isopropylthiophene-2-yl

 196

 methyl 2-chlorothiophene-5-yl

 197.

 methyl 2,5-dichlorothiophene-4-yl

 198.

 methyl 2,3-dichlorothiophene-5-yl

 199.

 methyl 2-chloro-3-nitrothiophene-5-yl

 200.

 methyl 2- (phenylsulfonyl) -thiophene-5-yl

 201.

 methyl 2- (pyridin-2-yl) thiophene-5-yl

 202.

 methyl 2- (5- (trifluoromethyl) isoxazol-3-yl) -thiophene-5-yl

 203

 methyl 2- (2-methylthiazol-4-yl) -thiophene-5-yl

 204.

 methyl 1-methyl-1H-imidazol-4-yl

 205.

 methyl 1,2-dimethyl-1H-imidazol-4-yl

 206.

 methyl 3,5-dimethylisoxazol-4-yl

 207.

 methyl thiazol-2-yl

 208.

 methyl 4-methylthiazol-2-yl

 209

 methyl 4-isopropylthiazol-2-yl

 210.

 methyl 4-trifluoromethylthiazol-2-yl

 211.

 methyl 5-methylthiazol-2-yl

 212.

 methyl 5-isopropylthiazol-2-yl

 213

 methyl 5-trifluoromethylthiazol-2-yl

 Do not.

 R1 Ar

 214.

 methyl 2,4-dimethylthiazol-5-yl

 215.

 methyl 2-acetamido-4-methylthiazol-5-yl

 216.

 methyl 4H- [1,2,4] triazol-3-yl

 217

 methyl 5-methyl-4H- [1,2,4] triazol-3-yl

 218.

 methyl 4-methyl-4H- [1,2,4] triazol-3-yl

 219.

 methyl 5-isopropyl-4H- [1,2,4] triazol-3-yl

 220.

 methyl 5-trifluoromethyl-4H- [1,2,4] triazol-3-yl

 221

 methyl 4,5-dimethyl-4H- [1,2,4] triazol-3-yl

 222

 methyl 5-isopropyl-4-methyl-4H- [1,2,4] triazol-3-yl

 223

 methyl 5-trifluoromethyl-4-methyl-4H- [1,2,4] triazol-3-yl

 224

 methyl [1,3,4] thiadiazol-2-yl

 225.

 methyl 5-methyl- [1,3,4] thiadiazol-2-yl

 226

 methyl 5-isopropyl- [1,3,4] thiadiazol-2-yl

 227

 methyl 5-trifluoromethyl- [1,3,4] thiadiazol-2-yl

 228

 methyl 3-bromo-2-chloropyrid-5-yl

 229

 methyl 2- (4-morpholino) pyrid-5-yl

 230.

 methyl 2-phenoxypyrid-5-yl

 231.

 methyl (2-isopropyl) -pyrimidin-5-yl

 232.

 methyl (5-isopropyl) -pyrimidin-2-yl

 233

 methyl 8-quinolyl

 2. 3. 4.

 methyl 5-isoquinolyl

 235

 methyl 2- (trifluoroacetyl) -1,2,3,4-tetrahydroisoquinolin-7-yl

 236.

 methyl 5-chloro-3-methylbenzothiophene-2-yl

 237

 methyl 3,4-dihydro-4-methyl-2H-benzo [b] [1,4] oxazinyl

 238.

 methyl benzothiazol-6-yl

 239

 methyl benzo [2,1,3] oxadiazol-4-yl

 240.

 methyl 5-chlorobenzo [2,1,3] oxadiazol-4-yl

  Do not.

 R1 Ar

 241

 methyl 7-chlorobenzo [2,1,3] oxadiazol-4-yl

 242

 methyl benzo [2,1,3] thiadiazol-4-yl

 243

 methyl 6-chloroimidazo [2,1-b] thiazolyl

 244

 ethyl 4- (trifluoromethoxy) -phenyl

 245

 ethyl 3- (trifluoromethoxy) -phenyl

 246

 ethyl 4-cyanophenyl

 247

 ethyl 4-methylphenyl

 248

 ethyl 4-ethylphenyl

 249

 ethyl 4-propylphenyl

 250

 ethyl 4-methoxyphenyl

 251

 ethyl 4-fluorophenyl

 252

 ethyl 4-chlorophenyl

 253

 ethyl 4-bromophenyl

 254

 ethyl 3- (trifluoromethyl) phenyl

 255

 ethyl 4- (trifluoromethyl) phenyl

 256.

 ethyl 2- (trifluoromethyl) phenyl

 257

 ethyl 3,4-difluorophenyl

 258

 ethyl 4-bromo-3-fluorophenyl

 259

 ethyl 4-bromo-2-fluorophenyl

 260.

 ethyl 4-bromo-2,5-difluorophenyl

 261

 ethyl 2-fluoro-4-isopropylphenyl

 262

 ethyl 4-hydroxyphenyl

 263

 ethyl 4-isopropylphenyl

 264

 ethyl 4-sec-butylphenyl

 265

 ethyl 4-isobutylphenyl

 266

 ethyl 4- (1,1-dimethylpropyl) -phenyl

 267

 ethyl 4-vinylphenyl

 268

 ethyl 4-isopropenylphenyl

 269

 ethyl 4- (fluoromethyl) phenyl

 Do not.

 R1 Ar

 270.

 ethyl 3- (fluoromethyl) phenyl

 271

 ethyl 2- (fluoromethyl) phenyl

 272

 ethyl 4- (difluoromethyl) phenyl

 273

 ethyl 3- (difluoromethyl) phenyl

 274

 ethyl 2- (difluoromethyl) phenyl

 275

 ethyl 4- (1-fluoroethyl) -phenyl

 276

 ethyl 4 - ((S) -1-fluoroethyl) -phenyl

 277

 ethyl 4 - ((R) -1-fluoroethyl) -phenyl

 278.

 ethyl 4- (2-fluoroethyl) -phenyl

 279.

 ethyl 4- (1,1-difluoroethyl) -phenyl

 280.

 ethyl 4- (2,2-difluoroethyl) -phenyl

 281

 ethyl 4- (2,2,2-trifluoroethyl) -phenyl

 282

 ethyl 4- (3-fluoropropyl) -phenyl

 283

 ethyl 4- (2-fluoropropyl) -phenyl

 284

 ethyl 4 - ((S) -2-fluoropropyl) -phenyl

 285

 ethyl 4 - ((R) -2-fluoropropyl) -phenyl

 286

 ethyl 4- (3,3-difluoropropyl) -phenyl

 287

 ethyl 4- (3,3,3-trifluoropropyl) -phenyl

 288

 ethyl 4- (1-fluoro-1-methylethyl) -phenyl

 289

 ethyl 4- (2-fluoro-1-methylethyl) -phenyl

 290.

 ethyl 4 - ((S) -2-fluoro-1-methylethyl) -phenyl

 291.

 ethyl 4 - ((R) -2-fluoro-1-methylethyl) -phenyl

 292

 ethyl 4- (2,2-difluoro-1-methylethyl) -phenyl

 293

 ethyl 4 - ((S) 2,2-difluoro-1-methylethyl) -phenyl

 294

 ethyl 4 - ((R) -2,2-difluoro-1-methylethyl) -phenyl

 295

 ethyl 4- (2,2,2-trifluoro-1-methylethyl) -phenyl

 296.

 ethyl 4 - ((S) -2,2,2-trifluoro-1-methylethyl) -phenyl

 297

 ethyl 4 - ((R) -2,2,2-trifluoro-1-methylethyl) -phenyl

 298.

 ethyl 4- (2-fluoro-1-fluoromethylethyl) -phenyl

 Do not.

 R1 Ar

 299.

 ethyl 4- (1-difluoromethyl-2,2-difluoroethyl) -phenyl

 300

 ethyl 4- (1,1-dimethyl-2-fluoroethyl) -phenyl

 301

 ethyl 4-ethoxyphenyl

 302

 ethyl 4-propoxyphenyl

 303

 ethyl 4-isopropoxyphenyl

 304.

 ethyl 4-butoxyphenyl

 305

 ethyl 4- (fluoromethoxy) -phenyl

 306

 ethyl 4- (difluoromethoxy) -phenyl

 307

 ethyl 4- (2-fluoroethoxy) -phenyl

 308

 ethyl 4- (2,2-difluoroethoxy) -phenyl

 309

 ethyl 4- (2,2,2-trifluoroethoxy) -phenyl

 310.

 ethyl 4- (1,1,2,2-tetrafluoroethoxy) -phenyl

 311

 ethyl 4-cyclopropylphenyl

 312

 ethyl 4-cyclobutylphenyl

 313

 ethyl 4-cylopentylphenyl

 314

 ethyl 4- (2,2-difluorocyclopropyl) -phenyl

 315

 ethyl 3-fluoro-4-isopropylphenyl

 316

 ethyl 4- (1-hydroxy-1-methylethyl) -phenyl

 317

 ethyl 4- (2-hydroxy-2-methylpropyl) -phenyl

 318

 ethyl 4-acetylphenyl

 319.

 ethyl 4-carboxyphenyl

 320.

 ethyl 4- (O-benzyl) -phenyl

 321.

 ethyl 4- (2-methoxyethoxy) -phenyl

 322

 ethyl 4- (CH2-N (CH3) 2) -phenyl

 323

 ethyl 4- (NH-CO-NH2) -phenyl

 324

 ethyl 4- (methylsulfanyl) -phenyl

 325.

 ethyl 4- (fluoromethylsulfanyl) -phenyl

 326

 ethyl 4- (difluoromethylsulfanyl) -phenyl

 327

 ethyl 4- (trifluoromethylsulfanyl) -phenyl

 Do not.

 R1 Ar

 328

 ethyl 4- (methylsulfonyl) -phenyl

 329.

 ethyl 4- (N-methoxy-N-methyl-amino) -phenyl

 330.

 ethyl 4- (methoxyamino) -phenyl

 331.

 ethyl 4- (ethoxyamino) -phenyl

 332

 ethyl 4- (N-methylaminooxy) -phenyl

 333.

 ethyl 4- (N, N-dimethylaminooxy) -phenyl

 334.

 ethyl 4- (azetidin-1-yl) -phenyl

 335.

 ethyl 4- (2-methylazetidin-1-yl) -phenyl

 336.

 ethyl 4 - ((S) -2-methylazetidin-1-yl) -phenyl

 337.

 ethyl 4 - ((R) -2-methylazetidin-1-yl) -phenyl

 338.

 ethyl 4- (3-fluoroazetidin-1-yl) -phenyl

 339

 ethyl 4- (3-methoxyazetidin-1-yl) -phenyl

 340.

 ethyl 4- (3-hydroxyazetidin-1-yl) -phenyl

 341.

 ethyl 4- (pyrrolidin-1-yl) -phenyl

 342

 ethyl 4- (pyrrolidin-2-yl) -phenyl

 343

 ethyl 4 - ((S) -pyrrolidin-2-yl) -phenyl

 344.

 ethyl 4 - ((R) -pyrrolidin-2-yl) -phenyl

 3. 4. 5.

 ethyl 4- (pyrrolidin-3-yl) -phenyl

 346.

 ethyl 4 - ((S) pyrrolidin-3-yl) -phenyl

 347.

 ethyl 4 - ((R) -pyrrolidin-3-yl) -phenyl

 348.

 ethyl 4- (2-fluoropyrrolidin-1-yl) -phenyl

 349.

 ethyl 4 - ((S) -2-fluoropyrrolidin-1-yl) -phenyl

 350

 ethyl 4 - ((R) -2-fluoropyrrolidin-1-yl) -phenyl

 351

 ethyl 4- (3-fluoropyrrolidin-1-yl) -phenyl

 352

 ethyl 4 - ((S) -3-fluoropyrrolidin-1-yl) -phenyl

 353

 ethyl 4 - ((R) -3-fluoropyrrolidin-1-yl) -phenyl

 354

 ethyl 4- (2,2-difluoropyrrolidin-1-yl) -phenyl

 355

 ethyl 4- (3,3-difluoropyrrolidin-1-yl) -phenyl

 356

 ethyl 4- (2-methylpyrrolidin-1-yl) -phenyl

 Do not.

 R1 Ar

 357

 ethyl 4 - ((S) -2-methylpyrrolidin-1-yl) -phenyl

 358

 ethyl 4 - ((R) -2-methylpyrrolidin-1-yl) -phenyl

 359.

 ethyl 4- (3-methylpyrrolidin-1-yl) -phenyl

 360

 ethyl 4 - ((S) -3-methylpyrrolidin-1-yl) -phenyl

 361.

 ethyl 4 - ((R) -3-methylpyrrolidin-1-yl) -phenyl

 362

 ethyl 4- (1-methylpyrrolidin-2-yl) -phenyl

 363

 ethyl 4 - ((S) -1-methylpyrrolidin-2-yl) -phenyl

 364

 ethyl 4 - ((R) -1-methylpyrrolidin-2-yl) -phenyl

 365.

 ethyl 4- (1-methylpyrrolidin-3-yl) -phenyl

 366.

 ethyl 4 - ((S) -1-methylpyrrolidin-3-yl) -phenyl

 367

 ethyl 4 - ((R) -1-methylpyrrolidin-3-yl) -phenyl

 368.

 ethyl 4- (2,2-dimethylpyrrolidin-1-yl) -phenyl

 369.

 ethyl 4- (3,3-dimethylpyrrolidin-1-yl) -phenyl

 370.

 ethyl 4- (2-trifluoromethylpyrrolidin-1-yl) -phenyl

 371

 ethyl 4 - ((S) -2-trifluoromethylpyrrolidin-1-yl) -phenyl

 372

 ethyl 4 - ((R) -2-trifluoromethylpyrrolidin-1-yl) -phenyl

 373

 ethyl 4- (3-trifluoromethylpyrrolidin-1-yl) -phenyl

 374

 ethyl 4 - ((S) -3-trifluoromethylpyrrolidin-1-yl) -phenyl

 375

 ethyl 4 - ((R) -3-trifluoromethylpyrrolidin-1-yl) -phenyl

 376

 ethyl 4- (2-oxopyrrolidin-1-yl) -phenyl

 377

 ethyl 4- (2-oxo-oxazolidin-3-yl) -phenyl

 378

 ethyl 4- (piperidin-1-yl) -phenyl

 379

 ethyl 4- (2-methylpiperidin-1-yl) -phenyl

 380.

 ethyl 4 - ((S) -2-methylpiperidin-1-yl) -phenyl

 381.

 ethyl 4 - ((R) -2-methylpiperidin-1-yl) -phenyl

 382

 ethyl 4- (piperazin-1-yl) -phenyl

 383

 ethyl 4- (4-methylpiperazin-1-yl) -phenyl

 384

 ethyl 4- (morpholin-4-yl) -phenyl

 385

 ethyl 4- (thiomorpholin-4-yl) -phenyl

 Do not.

 R1 Ar

 386.

 ethyl 4- (1-oxo-thiomorpholin-4-yl) -phenyl

 387

 ethyl 4- (1,1-dioxo-thiomorpholin-4-yl) -phenyl

 388.

 ethyl 4- (pyrrol-1-yl) -phenyl

 389.

 ethyl 4- (pyrrol-2-yl) -phenyl

 390.

 ethyl 4- (pyrrol-3-yl) -phenyl

 391.

 ethyl 4- (1-methylpyrrol-2-yl) -phenyl

 392

 ethyl 4- (1-methylpyrrol-3-yl) -phenyl

 393

 ethyl 4- (furan-2-yl) -phenyl

 394.

 ethyl 4- (furan-3-yl) -phenyl

 395

 ethyl 4- (thiophene-2-yl) -phenyl

 396.

 ethyl 4- (thiophen-3-yl) -phenyl

 397

 ethyl 4- (5-propylthien-2-yl) -phenyl

 398.

 ethyl 4- (pyrazol-1-yl) -phenyl

 399.

 ethyl 4- (pyrazol-3-yl) -phenyl

 400

 ethyl 4- (pyrazol-4-yl) -phenyl

 401

 ethyl 4- (1-methyl-1H-pyrazol-4-yl) -phenyl

 402

 ethyl 4- (1-ethyl-1H-pyrazol-4-yl) -phenyl

 403

 ethyl 4- (1-methyl-1H-pyrazol-5-yl) -phenyl

 404.

 ethyl 4- (1H-imidazol-2-yl) -phenyl

 405

 ethyl 4- (imidazol-1-yl) -phenyl

 406

 ethyl 4- (1-methylimidazol-2-yl) -phenyl

 407

 ethyl 4- (oxazol-2-yl) -phenyl

 408

 ethyl 4- (oxazol-4-y1) -phenyl

 409

 ethyl 4- (oxazol-5-yl) -phenyl

 410.

 ethyl 4- (isoxazol-3-yl) -phenyl

 411

 ethyl 4- (isoxazol-4-yl) -phenyl

 412

 ethyl 4- (isoxazol-5-yl) -phenyl

 413

 ethyl 4 - ([1,2,3] -triazol-1-yl) -phenyl

 414

 ethyl 4 - ([1,2,4] -triazol-1-yl) -phenyl

 Do not.

 R1 Ar

 415

 ethyl 4 - ([1,2,3] -triazol-2-yl) -phenyl

 416

 ethyl 4- (4H- [1,2,4] -triazol-3-yl) -phenyl

 417

 ethyl 4 - ([1,2,4] -triazol-4-yl) -phenyl

 418

 ethyl 4- (2H- [1,2,3] -triazol-4-yl) -phenyl

 419.

 ethyl 4- (4-methyl-4H- [1,2,4] -triazol-3-yl) -phenyl

 420.

 ethyl 4- (2-methyl-2H- [1,2,3] -triazol-4-yl) -phenyl

 421

 ethyl 4 - ([1,3,4] -oxadiazol-2-yl) -phenyl

 422

 ethyl 4 - ([1,2,4] -oxadiazol-3-yl) -phenyl

 423

 ethyl 4 - ([1,2,4] -oxadiazol-5-yl) -phenyl

 424

 ethyl 4 - ([1,2,3] -oxadiazol-4-yl) -phenyl

 425

 ethyl 4 - ([1,2,3] -oxadiazol-5-yl) -phenyl

 426

 ethyl 4 - ([1,2,3] -thiadiazol-4-yl) -phenyl

 427

 ethyl 4- (1H-tetrazol-5-yl) -phenyl

 428

 ethyl 4- (tetrazol-1-yl) -phenyl

 429

 ethyl 4- (2-methyl-2H-tetrazol-5-yl) -phenyl

 430

 ethyl 4- (1-methyl-1H-tetrazol-5-yl) -phenyl

 431

 ethyl 4-furazan-3-yl-phenyl

 432

 ethyl 4- (pyrid-2-yl) -phenyl

 433

 ethyl 4- (pyrid-3-yl) -phenyl

 434

 ethyl 4- (pyrid-4-yl) -phenyl

 435

 ethyl 4- (pyrimidin-2-yl) -phenyl

 436

 ethyl 4- (pyrimidin-4-yl) -phenyl

 437

 ethyl 4- (pyrimidin-5-yl) -phenyl

 438

 ethyl 5-isopropylthiophene-2-yl

 439

 ethyl 2-chlorothiophene-5-yl

 440

 ethyl 2,5-dichlorothiophene-4-yl

 441

 ethyl 2,3-dichlorothiophene-5-yl

 442

 ethyl 2-chloro-3-nitrothiophene-5-yl

 443

 ethyl 2- (phenylsulfonyl) -thiophene-5-yl

 Do not.

 R1 Ar

 444

 ethyl 2- (pyridin-2-yl) thiophene-5-yl

 445

 ethyl 2- (5- (trifluoromethyl) isoxazol-3-yl) -thiophene-5-yl

 446

 ethyl 2- (2-methylthiazol-4-yl) -thiophene-5-yl

 447

 ethyl 1-methyl-1H-imidazol-4-yl

 448

 ethyl 1,2-dimethyl-1H-imidazol-4-yl

 449

 ethyl 3,5-dimethylisoxazol-4-yl

 450.

 ethyl thiazol-2-yl

 451

 ethyl 4-methylthiazol-2-yl

 452

 ethyl 4-isopropylthiazol-2-yl

 453

 ethyl 4-trifluoromethylthiazol-2-yl

 454

 ethyl 5-methylthiazol-2-yl

 455

 ethyl 5-isopropylthiazol-2-yl

 456

 ethyl 5-trifluoromethylthiazol-2-yl

 457

 ethyl 2,4-dimethylthiazol-5-yl

 458

 ethyl 2-acetamido-4-methylthiazol-5-yl

 459

 ethyl 4H- [1,2,4] triazol-3-yl

 460

 ethyl 5-methyl-4H- [1,2,4] triazol-3-yl

 461.

 ethyl 4-methyl-4H- [1,2,4] triazol-3-yl

 462.

 ethyl 5-isopropyl-4H- [1,2,4] triazol-3-yl

 463

 ethyl 5-trifluoromethyl-4H- [1,2,4] triazol-3-yl

 464.

 ethyl 4,5-dimethyl-4H- [1,2,4] triazol-3-yl

 465

 ethyl 5-isopropyl-4-methyl-4H- [1,2,4] triazol-3-yl

 466.

 ethyl 5-trifluoromethyl-4-methyl-4H- [1,2,4] triazol-3-yl

 467.

 ethyl [1,3,4] thiadiazol-2-yl

 468.

 ethyl 5-methyl- [1,3,4] thiadiazol-2-yl

 469.

 ethyl 5-isopropyl- [1,3,4] thiadiazol-2-yl

 470

 ethyl 5-trifluoromethyl- [1,3,4] thiadiazol-2-yl

 471

 ethyl 3-bromo-2-chloropyrid-5-yl

 472

 ethyl 2- (4-morpholino) -pyrid-5-yl

 Do not.

 R1 Ar

 473

 ethyl 2-phenoxypyrid-5-yl

 474

 ethyl (2-isopropyl) -pyrimidin-5-yl

 475

 ethyl (5-isopropyl) -pyrimidin-2-yl

 476

 8-quinolyl ethyl

 477

 ethyl 5-isoquinolyl

 478

 ethyl 2- (trifluoroacetyl) -1,2,3,4-tetrahydroisoquinolin-7-yl

 479

 ethyl 5-chloro-3-methylbenzothiophene-2-yl

 480.

 ethyl 3,4-dihydro-4-methyl-2H-benzo [b] [1,4] oxazinyl

 481

 ethyl benzothiazol-6-yl

 482

 ethyl benzo [2,1,3] oxadiazol-4-yl

 483

 ethyl 5-chlorobenzo [2,1,3] oxadiazol-4-yl

 484

 ethyl 7-chlorobenzo [2,1,3] oxadiazol-4-yl

 485

 ethyl benzo [2,1,3] thiadiazol-4-yl

 486

 ethyl 6-chloroimidazo [2,1-b] thiazolyl

 487

 propyl 4- (trifluoromethoxy) -phenyl

 488

 propyl 3- (trifluoromethoxy) -phenyl

 489

 4-cyanophenyl propyl

 490.

 propyl 4-methylphenyl

 491.

 propyl 4-ethylphenyl

 492

 propyl 4-propylphenyl

 493

 propyl 4-methoxyphenyl

 494.

 propyl 4-fluorophenyl

 495

 propyl 4-chlorophenyl

 496.

 propyl 4-bromophenyl

 497

 propyl 3- (trifluoromethyl) phenyl

 498.

 propyl 4- (trifluoromethyl) phenyl

 499.

 propyl 2- (trifluoromethyl) phenyl

 500

 propyl 3,4-difluorophenyl

 501

 propyl 4-bromo-3-fluorophenyl

 Do not.

 R1 Ar

 502

 propyl 4-bromo-2-fluorophenyl

 503

 propyl 4-bromo-2,5-difluorophenyl

 504

 propyl 2-fluoro-4-isopropylphenyl

 505

 propyl 4-hydroxyphenyl

 506

 propyl 4-isopropylphenyl

 507

 propyl 4-sec-butylphenyl

 508

 propyl 4-isobutylphenyl

 509

 propyl 4- (1,1-dimethylpropyl) -phenyl

 510

 propyl 4-vinylphenyl

 511

 propyl 4-isopropenylphenyl

 512.

 propyl 4- (fluoromethyl) phenyl

 513

 propyl 3- (fluoromethyl) phenyl

 514

 propyl 2- (fluoromethyl) phenyl

 515

 propyl 4- (difluoromethyl) phenyl

 516

 propyl 3- (difluoromethyl) phenyl

 517

 propyl 2- (difluoromethyl) phenyl

 518

 propyl 4- (1-fluoroethyl) -phenyl

 519.

 propyl 4 - ((S) -1-fluoroethyl) -phenyl

 520.

 propyl 4 - ((R) -1-fluoroethyl) -phenyl

 521

 propyl 4- (2-fluoroethyl) -phenyl

 522

 propyl 4- (1,1-difluoroethyl) -phenyl

 523

 propyl 4- (2,2-difluoroethyl) -phenyl

 524

 propyl 4- (2,2,2-trifluoroethyl) -phenyl

 525

 propyl 4- (3-fluoropropyl) -phenyl

 526

 propyl 4- (2-fluoropropyl) -phenyl

 527

 propyl 4 - ((S) -2-fluoropropyl) -phenyl

 528

 propyl 4 - ((R) -2-fluoropropyl) -phenyl

 529

 propyl 4- (3,3-difluoropropyl) -phenyl

 530

 propyl 4- (3,3,3-trifluoropropyl) -phenyl

 Do not.

 R1 Ar

 531.

 propyl 4- (1-fluoro-1-methylethyl) -phenyl

 532

 propyl 4- (2-fluoro-1-methylethyl) -phenyl

 533

 propyl 4 - ((S) -2-fluoro-1-methylethyl) -phenyl

 534.

 propyl 4 - ((R) -2-fluoro-1-methylethyl) -phenyl

 535

 propyl 4- (2,2-difluoro-1-methylethyl) -phenyl

 536.

 propyl 4 - ((S) -2,2-difluoro-1-methylethyl) -phenyl

 537

 propyl 4 - ((R) -2,2-difluoro-1-methylethyl) -phenyl

 538.

 propyl 4- (2,2,2-trifluoro-1-methylethyl) -phenyl

 539.

 propyl 4 - ((S) -2,2,2-trifluoro-1-methylethyl) -phenyl

 540

 propyl 4 - ((R) -2,2,2-trifluoro-1-methylethyl) -phenyl

 541.

 propyl 4- (2-fluoro-1-fluoromethylethyl) -phenyl

 542

 propyl 4- (1-difluoromethyl-2,2-difluoroethyl) -phenyl

 543

 propyl 4- (1,1-dimethyl-2-fluoroethyl) -phenyl

 544

 propyl 4-ethoxyphenyl

 545

 propyl 4-propoxyphenyl

 546.

 propyl 4-isopropoxyphenyl

 547

 propyl 4-butoxyphenyl

 548.

 propyl 4- (fluoromethoxy) -phenyl

 549.

 propyl 4- (difluoromethoxy) -phenyl

 550

 propyl 4- (2-fluoroethoxy) -phenyl

 551.

 propyl 4- (2,2-difluoroethoxy) -phenyl

 552

 propyl 4- (2,2,2-trifluoroethoxy) -phenyl

 553

 propyl 4- (1,1,2,2-tetrafluoroethoxy) -phenyl

 554.

 propyl 4-cyclopropylphenyl

 555

 propyl 4-cyclobutylphenyl

 556.

 propyl 4-cyclopentylphenyl

 557.

 propyl 4- (2,2-difluorocyclopropyl) -phenyl

 558.

 propyl 3-fluoro-4-isopropylphenyl

 559.

 propyl 4- (1-hydroxy-1-methylethyl) -phenyl

 Do not.

 R1 Ar

 560

 propyl 4- (2-hydroxy-2-methylpropyl) -phenyl

 561.

 propyl 4-acetylphenyl

 562.

 propyl 4-carboxyphenyl

 563

 propyl 4- (O-benzyl) -phenyl

 564.

 propyl 4- (2-methoxyethoxy) -phenyl

 565.

 propyl 4- (CH2-N (CH3) 2) -phenyl

 566.

 propyl 4- (NH-CO-NH2) -phenyl

 567.

 propyl 4- (methylsulfanyl) -phenyl

 568.

 propyl 4- (fluoromethylsulfanyl) -phenyl

 569.

 propyl 4- (difluoromethylsulfanyl) -phenyl

 570.

 propyl 4- (trifluoromethylsulfanyl) -phenyl

 571.

 propyl 4- (methylsulfonyl) -phenyl

 572.

 propyl 4- (N-methoxy-N-methyl-amino) -phenyl

 573

 propyl 4- (methoxyamino) -phenyl

 574.

 propyl 4- (ethoxyamino) -phenyl

 575

 propyl 4- (N-methylaminooxy) -phenyl

 576.

 propyl 4- (N, N-dimethylaminooxy) -phenyl

 577

 propyl 4- (azetidin-1-yl) -phenyl

 578.

 propyl 4- (2-methylazetidin-1-yl) -phenyl

 579.

 propyl 4 - ((S) -2-methylazetidin-1-yl) -phenyl

 580

 propyl 4 - ((R) -2-methylazetidin-1-yl) -phenyl

 581.

 propyl 4- (3-fluoroazetidin-1-yl) -phenyl

 582.

 propyl 4- (3-methoxyazetidin-1-yl) -phenyl

 583.

 propyl 4- (3-hydroxyazetidin-1-yl) -phenyl

 584.

 propyl 4- (pyrrolidin-1-yl) -phenyl

 585.

 propyl 4- (pyrrolidin-2-yl) -phenyl

 586.

 propyl 4 - ((S) -pyrrolidin-2-yl) -phenyl

 587.

 propyl 4 - ((R) -pyrrolidin-2-yl) -phenyl

 588.

 propyl 4- (pyrrolidin-3-yl) -phenyl

 Do not.

 R1 Ar

 589.

 propyl 4 - ((S) -pyrrolidin-3-yl) -phenyl

 590

 propyl 4 - ((R) -pyrrolidin-3-yl) -phenyl

 591.

 propyl 4- (2-fluoropyrrolidin-1-yl) -phenyl

 592

 propyl 4 - ((S) -2-fluoropyn-olidin-1-yl) -phenyl

 593

 propyl 4 - ((R) -2-fluoropyrrolidin-1-yl) -phenyl

 594

 propyl 4- (3-fluoropyrrolidin-1-yl) -phenyl

 595

 propyl 4 - ((S) -3-fluoropyrrolidin-1-yl) -phenyl

 596

 propyl 4 - ((R) -3-fluoropyrrolidin-1-yl) -phenyl

 597

 propyl 4- (2,2-difluoropyrrolidin-1-yl) -phenyl

 598

 propyl 4- (3,3-difluoropyrrolidin-1-yl) -phenyl

 599.

 propyl 4- (2-methylpyrrolidin-1-yl) -phenyl

 600.

 propyl 4 - ((S) -2-methylpyrrolidin-1-yl) -phenyl

 601

 propyl 4 - ((R) -2-methylpyrrolidin-1-yl) -phenyl

 602

 propyl 4- (3-methylpyrrolidin-1-yl) -phenyl

 603

 propyl 4 - ((S) -3-methylpyrrolidin-1-yl) -phenyl

 604

 propyl 4 - ((R) -3-methylpyrrolidin-1-yl) -phenyl

 605

 propyl 4- (1-methylpyrrolidin-2-yl) -phenyl

 606

 propyl 4 - ((S) -1-methylpyrrolidin-2-yl) -phenyl

 607

 propyl 4 - ((R) -1-methylpyrrolidin-2-yl) -phenyl

 608

 propyl 4- (1-methylpyrrolidin-3-yl) -phenyl

 609

 propyl 4 - ((S) -1-methylpyrrolidin-3-yl) -phenyl

 610

 propyl 4 - ((R) -1-methylpyrrolidin-3-yl) -phenyl

 611

 propyl 4- (2,2-dimethylpyrrolidin-1-yl) -phenyl

 612

 propyl 4- (3,3-dimethylpyrrolidin-1-yl) -phenyl

 613

 propyl 4- (2-trifluoromethylpyrrolidin-1-yl) -phenyl

 614

 propyl 4 - ((S) -2-trifluoromethylpyrrolidin-1-yl) -phenyl

 615

 propyl 4 - ((R) -2-trifluoromethylpyrrolidin-1-yl) -phenyl

 616

 propyl 4- (3-trifluoromethylpyrrolidin-1-yl) -phenyl

 617

 propyl 4 - ((S) -3-trifluoromethylpyrrolidin-1-yl) -phenyl

 Do not.

 R1 Ar

 618

 propyl 4 - ((R) -3-trifluoromethylpyrrolidin-1-yl) -phenyl

 619.

 propyl 4- (2-oxopyrrolidin-1-yl) -phenyl

 620.

 propyl 4- (2-oxo-oxazolidin-3-yl) -phenyl

 621

 propyl 4- (piperidin-1-yl) -phenyl

 622

 propyl 4- (2-methylpiperidin-1-yl) -phenyl

 623

 propyl 4 - ((S) -2-methylpiperidin-1-yl) -phenyl

 624.

 propyl 4 - ((R) -2-methylpiperidin-1-yl) -phenyl

 625

 propyl 4- (piperazin-1-yl) -phenyl

 626

 propyl 4- (4-methylpiperazin-1-yl) -phenyl

 627

 propyl 4- (morpholin-4-yl) -phenyl

 628

 propyl 4- (thiomorpholin-4-yl) -phenyl

 629

 propyl 4- (1-oxo-thiomorpholin-4-yl) -phenyl

 630

 propyl 4- (1,1-dioxo-thiomorpholin-4-yl) -phenyl

 631

 propyl 4- (pyrrol-1-yl) -phenyl

 632

 propyl 4- (pyrrol-2-yl) -phenyl

 633

 propyl 4- (pyrrol-3-yl) -phenyl

 634.

 propyl 4- (1-methylpyrrol-2-yl) -phenyl

 635

 propyl 4- (1-methylpyrrol-3-yl) -phenyl

 636

 propyl 4- (furan-2-yl) -phenyl

 637

 propyl 4- (furan-3-yl) -phenyl

 638

 propyl 4- (thiophene-2-yl) -phenyl

 639

 propyl 4- (thiophene-3-yl) -phenyl

 640.

 propyl 4- (5-propylthien-2-yl) -phenyl

 641.

 propyl 4- (pyrazol-1-yl) -phenyl

 642

 propyl 4- (pyrazol-3-yl) -phenyl

 643

 propyl 4- (pyrazol-4-yl) -phenyl

 644.

 propyl 4- (1-methyl-1H-pyrazol-4-yl) -phenyl

 645.

 propyl 4- (1-ethyl-1H-pyrazol-4-yl) -phenyl

 646.

 propyl 4- (1-methyl-1H-pyrazol-5-yl) -phenyl

 Do not.

 R1 Ar

 647

 propyl 4- (1H-imidazol-2-yl) -phenyl

 648.

 propyl 4- (imidazol-1-yl) -phenyl

 649.

 propyl 4- (1-methylimidazol-2-yl) -phenyl

 650.

 propyl 4- (oxazol-2-yl) -phenyl

 651

 propyl 4- (oxazol-4-yl) -phenyl

 652

 propyl 4- (oxazol-5-yl) -phenyl

 653

 propyl 4- (isoxazol-3-yl) -phenyl

 654

 propyl 4- (isoxazol-4-yl) -phenyl

 655.

 propyl 4- (isoxazol-5-yl) -phenyl

 656

 propyl 4 - ([1,2,3] -triazol-1-yl) -phenyl

 657

 propyl 4 - ([1,2,4] -triazol-1-yl) -phenyl

 658

 propyl 4 - ([1,2,3] -triazol-2-yl) -phenyl

 659

 propyl 4- (4H- [1,2,4] -triazol-3-yl) -phenyl

 660

 propyl 4 - ([1,2,4] -triazol-4-yl) -phenyl

 661.

 propyl 4- (2H- [1,2,3] -triazol-4-yl) -phenyl

 662.

 propyl 4- (4-methyl-4H- [1,2,4] -triazol-3-yl) -phenyl

 663

 propyl 4- (2-methyl-2H- [1,2,3] -triazol-4-yl) -phenyl

 664.

 propyl 4 - ([1,3,4] -oxadiazol-2-yl) -phenyl

 665

 propyl 4 - ([1,2,4] -oxadiazol-3-yl) -phenyl

 666.

 propyl 4 - ([1,2,4] -oxadiazol-5-yl) -phenyl

 667

 propyl 4 - ([1,2,3] -oxadiazol-4-yl) -phenyl

 668.

 propyl 4 - ([1,2,3] -oxadiazol-5-yl) -phenyl

 669.

 propyl 4 - ([1,2,3] -thiadiazol-4-yl) -phenyl

 670

 propyl 4- (1H-tetrazol-5-yl) -phenyl

 671.

 propyl 4- (tetrazol-1-yl) -phenyl

 672.

 propyl 4- (2-methyl-2H-tetrazol-5-yl) -phenyl

 673.

 propyl 4- (1-methyl-1H-tetrazol-5-yl) -phenyl

 674.

 propyl 4-furazan-3-yl-phenyl

 675

 propyl 4- (pyrid-2-yl) -phenyl

 Do not.

 R1 Ar

 676.

 propyl 4- (pyrid-3-yl) -phenyl

 677.

 propyl 4- (pyrid-4-yl) -phenyl

 678.

 propyl 4- (pyrimidin-2-yl) -phenyl

 679.

 propyl 4- (pyrimidin-4-yl) -phenyl

 680

 propyl 4- (pyrimidin-5-yl) -phenyl

 681.

 propyl 5-isopropylthiophene-2-yl

 682.

 propyl 2-chlorothiophene-5-yl

 683

 propyl 2,5-dichlorothiophene-4-yl

 684.

 propyl 2,3-dichlorothiophene-5-yl

 685.

 propyl 2-chloro-3-nitrothiophene-5-yl

 686.

 propyl 2- (phenylsulfonyl) -thiophene-5-yl

 687.

 propyl 2- (pyridin-2-yl) thiophene-5-yl

 688.

 propyl 2- (5- (trifluoromethyl) isoxazol-3-yl) -thiophene-5-yl

 689.

 propyl 2- (2-methylthiazol-4-yl) -thiophene-5-yl

 690.

 propyl 1-methyl-1H-imidazol-4-yl

 691.

 propyl 1,2-dimethyl-1H-imidazol-4-yl

 692.

 propyl 3,5-dimethylisoxazol-4-yl

 693

 propyl thiazol-2-yl

 694.

 propyl 4-methylthiazol-2-yl

 695.

 propyl 4-isopropylthiazol-2-yl

 696.

 propyl 4-trifluoromethylthiazol-2-yl

 697.

 propyl 5-methylthiazol-2-yl

 698.

 propyl 5-isopropylthiazol-2-yl

 699.

 propyl 5-trifluoromethylthiazol-2-yl

 700.

 propyl 2,4-dimethylthiazol-5-yl

 701

 propyl 2-acetamido-4-methylthiazol-5-yl

 702

 propyl 4H- [1,2,4] triazol-3-yl

 703

 propyl 5-methyl-4H- [1,2,4] triazol-3-yl

 704

 propyl 4-methyl-4H- [1,2,4] triazol-3-yl

 Do not.

 R1 Ar

 705.

 propyl 5-isopropyl-4H- [1,2,4] triazol-3-yl

 706.

 propyl 5-trifluoromethyl-4H- [1,2,4] triazol-3-yl

 707.

 Propyl 4,5-dimethyl-4H- [1,2,4] triazol-3-yl

 708.

 propyl 5-isopropyl-4-methyl-4H- [1,2,4] triazol-3-yl

 709

 propyl 5-trifluoromethyl-4-methyl-4H- [1,2,4] triazol-3-yl

 710

 propyl [1,3,4] thiadiazol-2-yl

 711

 propyl 5-methyl- [1,3,4] thiadiazol-2-yl

 712

 propyl 5-isopropyl- [1,3,4] thiadiazol-2-yl

 713

 propyl 5-trifluoromethyl- [1,3,4] thiadiazol-2-yl

 714

 propyl 3-bromo-2-chloropyrid-5-yl

 715

 propyl 2- (4-morpholino) -pyrid-5-yl

 716

 propyl 2-phenoxypyrid-5-yl

 717

 propyl (2-isopropyl) -pyrimidin-5-yl

 718

 propyl (5-isopropyl) -pyrimidin-2-yl

 719

 8-quinolyl propyl

 720.

 propyl 5-isoquinolyl

 721

 propyl 2- (trifluoroacetyl) -1,2,3,4-tetrahydroisoquinolin-7-yl

 722

 propyl 5-chloro-3-methylbenzothiophene-2-yl

 723

 propyl 3,4-dihydro-4-methyl-2H-benzo [b] [1,4] oxazinyl

 724

 propyl benzothiazol-6-yl

 725

 propyl benzo [2,1,3] oxadiazol-4-yl

 726

 propyl 5-chlorobenzo [2,1,3] oxadiazol-4-yl

 727

 propyl 7-chlorobenzo [2,1,3] oxadiazol-4-yl

 728

 propyl benzo [2,1,3] thiadiazol-4-yl

 729

 propyl 6-chloroimidazo [2,1-b] thiazolyl

 730

 3-fluoropropyl 4-methylphenyl

 731

 3-fluoropropyl 4-ethylphenyl

 732

 3-fluoropropyl 4-propylphenyl

 733

 3-fluoropropyl 4-isopropylphenyl

 Do not.

 R1 Ar

 734

 3-fluoropropyl 4-sec-butylphenyl

 735

 3-fluoropropyl 4-isobutylphenyl

 736

 3-fluoropropyl 4- (1,1-dimethylpropyl) -phenyl

 737

 3-fluoropropyl 4-vinylphenyl

 738

 3-fluoropropyl 4-isopropenylphenyl

 739

 3-fluoropropyl 4-fluorophenyl

 740

 3-fluoropropyl 4-chlorophenyl

 741

 3-fluoropropyl 4-bromophenyl

 742

 3-fluoropropyl 4- (fluoromethyl) phenyl

 743

 3-fluoropropyl 3- (fluoromethyl) phenyl

 744

 3-fluoropropyl 2- (fluoromethyl) phenyl

 745

 3-fluoropropyl 4- (difluoromethyl) phenyl

 746

 3-fluoropropyl 3- (difluoromethyl) phenyl

 747

 3-fluoropropyl 2- (difluoromethyl) phenyl

 748

 3-fluoropropyl 4- (trifluoromethyl) phenyl

 749

 3-fluoropropyl 3- (trifluoromethyl) phenyl

 750

 3-fluoropropyl 2- (trifluoromethyl) phenyl

 751

 3-fluoropropyl 4- (1-fluoroethyl) -phenyl

 752

 3-fluoropropyl 4 - ((S) -1-fluoroethyl) -phenyl

 753

 3-fluoropropyl 4 - ((R) -1-fluoroethyl) -phenyl

 754

 3-fluoropropyl 4- (2-fluoroethyl) -phenyl

 755

 3-fluoropropyl 4- (1,1-difluoroethyl) -phenyl

 756

 3-fluoropropyl 4- (2,2-difluoroethyl) -phenyl

 757

 3-fluoropropyl 4- (2,2,2-trifluoroethyl) -phenyl

 758

 3-fluoropropyl 4- (3-fluoropropyl) -phenyl

 759

 3-fluoropropyl 4- (2-fluoropropyl) -phenyl

 760

 3-fluoropropyl 4 - ((S) -2-fluoropropyl) -phenyl

 761

 3-fluoropropyl 4 - ((R) -2-fluoropropyl) -phenyl

 762

 3-fluoropropyl 4- (3,3-difluoropropyl) -phenyl

 Do not.

 R1 Ar

 763

 3-fluoropropyl 4- (3,3,3-trifluoropropyl) -phenyl

 764

 3-fluoropropyl 4- (1-fluoro-1-methylethyl) -phenyl

 765

 3-fluoropropyl 4- (2-fluoro-1-methylethyl) -phenyl

 766

 3-fluoropropyl 4 - ((S) -2-fluoro-1-methylethyl) -phenyl

 767.

 3-fluoropropyl 4 - ((R) -2-fluoro-1-methylethyl) -phenyl

 768

 3-fluoropropyl 4- (2,2-difluoro-1-methylethyl) -phenyl

 769

 3-fluoropropyl 4 - ((S) -2,2-difluoro-1-methylethyl) -phenyl

 770

 3-fluoropropyl 4 - ((R) -2,2-difluoro-1-methylethyl) -phenyl

 771

 3-fluoropropyl 4- (2,2,2-trifluoro-1-methylethyl) -phenyl

 772

 3-fluoropropyl 4 - ((S) -2,2,2-trifluoro-1-methylethyl) -phenyl

 773

 3-fluoropropyl 4 - ((R) -2,2,2-trifluoro-1-methylethyl) -phenyl

 774

 3-fluoropropyl 4- (2-fluoro-1-fluoromethylethyl) -phenyl

 775

 3-fluoropropyl 4- (1-difluoromethyl-2,2-difluoroethyl) -phenyl

 776

 3-fluoropropyl 4- (1,1-dimethyl-2-fluoroethyl) -phenyl

 777

 3-fluoropropyl 4-methoxyphenyl

 778

 3-fluoropropyl 4-ethoxyphenyl

 779

 3-fluoropropyl 4-propoxyphenyl

 780

 3-fluoropropyl 4-isopropoxyphenyl

 781.

 3-fluoropropyl 4-butoxyphenyl

 782.

 3-fluoropropyl 4- (fluoromethoxy) -phenyl

 783

 3-fluoropropyl 4- (difluoromethoxy) -phenyl

 784.

 3-fluoropropyl 4- (trifluoromethoxy) -phenyl

 785.

 3-fluoropropyl 3- (trifluoromethoxy) -phenyl

 786.

 3-fluoropropyl 4- (2-fluoroethoxy) -phenyl

 787.

 3-fluoropropyl 4- (2,2-difluoroethoxy) -phenyl

 788

 3-fluoropropyl 4- (2,2,2-trifluoroethoxy) -phenyl

 789.

 3-fluoropropyl 4- (1,1,2,2-tetrafluoroethoxy) -phenyl

 790

 3-fluoropropyl 4-cyclopropylphenyl

 791.

 3-fluoropropyl 4-cyclobutylphenyl

 Do not.

 R1 Ar

 792

 3-fluoropropyl 4-cyclopentylphenyl

 793.

 3-fluoropropyl 4- (2,2-difluorocyclopropyl) -phenyl

 794.

 3-fluoropropyl 3,4-difluorophenyl

 795

 3-fluoropropyl 4-bromo-3-fluorophenyl

 796.

 3-fluoropropyl 4-bromo-2-fluorophenyl

 797.

 3-fluoropropyl 4-bromo-2,5-difluorophenyl

 798.

 3-fluoropropyl 2-fluoro-4-isopropylphenyl

 799

 3-fluoropropyl 3-fluoro-4-isopropylphenyl

 800.

 3-fluoropropyl 4- (1-hydroxy-1-methylethyl) -phenyl

 801

 3-fluoropropyl 4- (2-hydroxy-2-methylpropyl) -phenyl

 802.

 3-fluoropropyl 4-acetylphenyl

 803

 3-fluoropropyl 4-carboxyphenyl

 804

 3-fluoropropyl 4-cyanophenyl

 805

 3-fluoropropyl 4-hydroxyphenyl

 806

 3-fluoropropyl 4- (O-benzyl) -phenyl

 807

 3-fluoropropyl 4- (2-methoxyethoxy) -phenyl

 808

 3-fluoropropyl 4- (CH2-N (CH3) 2) -phenyl

 809

 3-fluoropropyl 4- (NH-CO-NH2) -phenyl

 810

 3-fluoropropyl 4- (methylsulfanyl) -phenyl

 811

 3-fluoropropyl 4- (fluoromethylsulfanyl) -phenyl

 812

 3-fluoropropyl 4- (difluoromethylsulfanyl) -phenyl

 813

 3-fluoropropyl 4- (trifluoromethylsulfanyl) -phenyl

 814

 3-fluoropropyl 4- (methylsulfonyl) -phenyl

 815

 3-fluoropropyl 4- (N-methoxy-N-methyl-amino) -phenyl

 816

 3-fluoropropyl 4- (methoxyamino) -phenyl

 817

 3-fluoropropyl 4- (ethoxyamino) -phenyl

 818

 3-fluoropropyl 4- (N-methylaminooxy) -phenyl

 819.

 3-fluoropropyl 4- (N, N-dimethylaminooxy) -phenyl

 820

 3-fluoropropyl 4- (azetidin-1-yl) -phenyl

 Do not.

 R1 Ar

 821

 3-fluoropropyl 4- (2-methylazetidin-1-yl) -phenyl

 822

 3-fluoropropyl 4 - ((S) -2-methylazetidin-1-yl) -phenyl

 823

 3-fluoropropyl 4 - ((R) -2-methylazetidin-1-yl) -phenyl

 824

 3-fluoropropyl 4- (3-fluoroazetidin-1-yl) -phenyl

 825

 3-fluoropropyl 4- (3-methoxyazetidin-1-yl) -phenyl

 826

 3-fluoropropyl 4- (3-hydroxyazetidin-1-yl) -phenyl

 827

 3-fluoropropyl 4- (pyrrolidin-1-yl) -phenyl

 828

 3-fluoropropyl 4- (pyrrolidin-2-yl) -phenyl

 829

 3-fluoropropyl 4 - ((S) -pyrrolidin-2-yl) -phenyl

 830

 3-fluoropropyl 4 - ((R) -pyrrolidin-2-yl) -phenyl

 831

 3-fluoropropyl 4- (pyrrolidin-3-yl) -phenyl

 832

 3-fluoropropyl 4 - ((S) -pyrrolidin-3-yl) -phenyl

 833

 3-fluoropropyl 4 - ((R) -pyrrolidin-3-yl) -phenyl

 834

 3-fluoropropyl 4- (2-fluoropyrrolidin-1-yl) -phenyl

 835

 3-fluoropropyl 4 - ((S) -2-fluoropyrrolidin-1-yl) -phenyl

 836

 3-fluoropropyl 4 - ((R) -2-fluoropyrrolidin-1-yl) -phenyl

 837

 3-fluoropropyl 4- (3-fluoropyrrolidin-1-yl) -phenyl

 838

 3-fluoropropyl 4 - ((S) -3-fluoropyrrolidin-1-yl) -phenyl

 839

 3-fluoropropyl 4 - ((R) -3-fluoropyrrolidin-1-yl) -phenyl

 840

 3-fluoropropyl 4- (2,2-difluoropyrrolidin-1-yl) -phenyl

 841

 3-fluoropropyl 4- (3,3-difluoropyrrolidin-1-yl) -phenyl

 842

 3-fluoropropyl 4- (2-methylpyrrolidin-1-yl) -phenyl

 843

 3-fluoropropyl 4 - ((S) -2-methylpyrrolidin-1-yl) -phenyl

 844

 3-fluoropropyl 4 - ((R) -2-methylpyrrolidin-1-yl) -phenyl

 845

 3-fluoropropyl 4- (3-methylpyrrolidin-1-yl) -phenyl

 846

 3-fluoropropyl 4 - ((S) -3-methylpyrrolidin-1-yl) -phenyl

 847

 3-fluoropropyl 4 - ((R) -3-methylpyrrolidin-1-yl) -phenyl

 848

 3-fluoropropyl 4- (1-methylpyrrolidin-2-yl) -phenyl

 849

 3-fluoropropyl 4 - ((S) -1-methylpyrrolidin-2-yl) -phenyl

 Do not.

 R1 Ar

 850.

 3-fluoropropyl 4 - ((R) -1-methylpyrrolidin-2-yl) -phenyl

 851.

 3-fluoropropyl 4- (1-methylpyrrolidin-3-yl) -phenyl

 852

 3-fluoropropyl 4 - ((S) -1-methylpyrrolidin-3-yl) -phenyl

 853

 3-fluoropropyl 4 - ((R) -1-methylpyrrolidin-3-yl) -phenyl

 854

 3-fluoropropyl 4- (2,2-dimethylpyrrolidin-1-yl) -phenyl

 855

 3-fluoropropyl 4- (3,3-dimethylpyrrolidin-1-yl) -phenyl

 856.

 3-fluoropropyl 4- (2-trifluoromethylpyrrolidin-1-yl) -phenyl

 857

 3-fluoropropyl 4 - ((S) -2-trifluoromethylpyrrolidin-1-yl) -phenyl

 858

 3-fluoropropyl 4 - ((R) -2-trifluoromethylpyrrolidin-1-yl) -phenyl

 859

 3-fluoropropyl 4- (3-trifluoromethylpyrrolidin-1-yl) -phenyl

 860

 3-fluoropropyl 4 - ((S) -3-trifluoromethylpyrrolidin-1-yl) -phenyl

 861

 3-fluoropropyl 4 - ((R) -3-trifluoromethylpyrrolidin-1-yl) -phenyl

 862

 3-fluoropropyl 4- (2-oxopyrrolidin-1-yl) -phenyl

 863

 3-fluoropropyl 4- (2-oxo-oxazolidin-3-yl) -phenyl

 864

 3-fluoropropyl 4- (piperidin-1-yl) -phenyl

 865

 3-fluoropropyl 4- (2-methylpiperidin-1-yl) -phenyl

 866.

 3-fluoropropyl 4 - ((S) -2-methylpiperidin-1-yl) -phenyl

 867.

 3-fluoropropyl 4 - ((R) -2-methylpiperidin-1-yl) -phenyl

 868

 3-fluoropropyl 4- (piperazin-1-yl) -phenyl

 869

 3-fluoropropyl 4- (4-methylpiperazin-1-yl) -phenyl

 870

 3-fluoropropyl 4- (morpholin-4-yl) -phenyl

 871

 3-fluoropropyl 4- (thiomorpholin-4-yl) -phenyl

 872.

 3-fluoropropyl 4- (1-oxo-thiomorpholin-4-yl) -phenyl

 873

 3-fluoropropyl 4- (1,1-dioxo-thiomorpholin-4-yl) -phenyl

 874

 3-fluoropropyl 4- (pyrrol-1-yl) -phenyl

 875

 3-fluoropropyl 4- (pyrrol-2-yl) -phenyl

 876

 3-fluoropropyl 4- (pyrrol-3-yl) -phenyl

 877

 3-fluoropropyl 4- (1-methylpyrrol-2-yl) -phenyl

 878.

 3-fluoropropyl 4- (1-methylpyrrol-3-yl) -phenyl

 Do not.

 R1 Ar

 879

 3-fluoropropyl 4- (furan-2-yl) -phenyl

 880

 3-fluoropropyl 4- (furan-3-yl) -phenyl

 881.

 3-fluoropropyl 4- (thiophene-2-yl) -phenyl

 882.

 3-fluoropropyl 4- (thiophene-3-yl) -phenyl

 883

 3-fluoropropyl 4- (5-propylthien-2-yl) -phenyl

 884.

 3-fluoropropyl 4- (pyrazol-1-yl) -phenyl

 885.

 3-fluoropropyl 4- (pyrazol-3-yl) -phenyl

 886.

 3-fluoropropyl 4- (pyrazol-4-yl) -phenyl

 887.

 3-fluoropropyl 4- (1-methyl-1H-pyrazol-4-yl) -phenyl

 888

 3-fluoropropyl 4- (1-ethyl-1H-pyrazol-4-yl) -phenyl

 889.

 3-fluoropropyl 4- (1-methyl-1H-pyrazol-5-yl) -phenyl

 890

 3-fluoropropyl 4- (1 H -imidazol-2-yl) -phenyl

 891

 3-fluoropropyl 4- (imidazol-1-yl) -phenyl

 892

 3-fluoropropyl 4- (1-methylimidazol-2-yl) -phenyl

 893,

 3-fluoropropyl 4- (oxazol-2-yl) -phenyl

 894.

 3-fluoropropyl 4- (oxazol-4-yl) -phenyl

 895.

 3-fluoropropyl 4- (oxazol-5-yl) -phenyl

 896.

 3-fluoropropyl 4- (isoxazol-3-yl) -phenyl

 897.

 3-fluoropropyl 4- (isoxazol-4-yl) -phenyl

 898.

 3-fluoropropyl 4- (isoxazol-5-yl) -phenyl

 899

 3-fluoropropyl 4 - ([1,2,3] -triazol-1-yl) -phenyl

 900.

 3-fluoropropyl 4 - ([1,2,4] -triazol-1-yl) -phenyl

 901

 3-fluoropropyl 4 - ([1,2,3] -triazol-2-yl) -phenyl

 902

 3-fluoropropyl 4- (4H- [1,2,4] -triazol-3-yl) -phenyl

 903

 3-fluoropropyl 4 - ([1,2,4] -triazol-4-yl) -phenyl

 904

 3-fluoropropyl 4- (2H- [1,2,3] -triazol-4-yl) -phenyl

 905

 3-fluoropropyl 4- (4-methyl-4H- [1,2,4] -triazol-3-yl) -phenyl

 906

 3-fluoropropyl 4- (2-methyl-2H- [1,2,3] -triazol-4-yl) -phenyl

 907

 3-fluoropropyl 4 - ([1,3,4] -oxadiazol-2-yl) -phenyl

 Do not.

 R1 Ar

 908

 3-fluoropropyl 4 - ([1,2,4] -oxadiazol-3-yl) -phenyl

 909

 3-fluoropropyl 4 - ([1,2,4] -oxadiazol-5-yl) -phenyl

 910

 3-fluoropropyl 4 - ([1,2,3] -oxadiazol-4-yl) -phenyl

 911

 3-fluoropropyl 4 - ([1,2,3] -oxadiazol-5-yl) -phenyl

 912

 3-fluoropropyl 4 - ([1,2,3] -thiadiazol-4-yl) -phenyl

 913

 3-fluoropropyl 4- (1H-tetrazol-5-yl) -phenyl

 914

 3-fluoropropyl 4- (tetrazol-1-yl) -phenyl

 915

 3-fluoropropyl 4- (2-methyl-2H-tetrazol-5-yl) -phenyl

 916.

 3-fluoropropyl 4- (1-methyl-1H-tetrazol-5-yl) -phenyl

 917.

 3-fluoropropyl 4-furazan-3-yl-phenyl

 918

 3-fluoropropyl 4- (pyrid-2-yl) -phenyl

 919.

 3-fluoropropyl 4- (pyrid-3-yl) -phenyl

 920.

 3-fluoropropyl 4- (pyrid-4-yl) -phenyl

 921

 3-fluoropropyl 4- (pyrimidin-2-yl) -phenyl

 922

 3-fluoropropyl 4- (pyrimidin-4-yl) -phenyl

 923

 3-fluoropropyl 4- (pyrimidin-5-yl) -phenyl

 924.

 3-fluoropropyl 5-isopropylthiophene-2-yl

 925

 3-fluoropropyl 2-chlorothiophene-5-yl

 926

 3-fluoropropyl 2,5-dichlorothiophene-4-yl

 927

 3-fluoropropyl 2,3-dichlorothiophene-5-yl

 928.

 3-fluoropropyl 2-chloro-3-nitrothiophene-5-yl

 929

 3-fluoropropyl 2- (phenylsulfonyl) -thiophene-5-yl

 930

 3-fluoropropyl 2- (pyridin-2-yl) thiophene-5-yl

 931

 3-fluoropropyl 2- (5- (trifluoromethyl) isoxazol-3-yl) -thiophene-5-yl

 932

 3-fluoropropyl 2- (2-methylthiazol-4-yl) -thiophene-5-yl

 933

 3-fluoropropyl 1-methyl-1H-imidazol-4-yl

 934.

 3-fluoropropyl 1,2-dimethyl-1H-imidazol-4-yl

 935

 3-fluoropropyl 3,5-dimethylisoxazol-4-yl

 936

 3-fluoropropyl thiazol-2-yl

 Do not.

 R1 Ar

 937

 3-fluoropropyl 4-methylthiazol-2-yl

 938

 3-fluoropropyl 4-isopropylthiazol-2-yl

 939.

 3-fluoropropyl 4-trifluoromethylthiazol-2-yl

 940

 3-fluoropropyl 5-methylthiazol-2-yl

 941

 3-fluoropropyl 5-isopropylthiazol-2-yl

 942

 3-fluoropropyl 5-trifluoromethylthiazol-2-yl

 943

 3-fluoropropyl 2,4-dimethylthiazol-5-yl

 944

 3-fluoropropyl 2-acetamido-4-methylthiazol-5-yl

 945

 3-fluoropropyl 4H- [1,2,4] triazol-3-yl

 946.

 3-fluoropropyl 5-methyl-4H- [1,2,4] triazol-3-yl

 947

 3-fluoropropyl 4-methyl-4H- [1,2,4] triazol-3-yl

 948

 3-fluoropropyl 5-isopropyl-4H- [1,2,4] triazol-3-yl

 949.

 3-fluoropropyl 5-trifluoromethyl-4H- [1,2,4] triazol-3-yl

 950

 3-fluoropropyl 4,5-dimethyl-4H- [1,2,4] triazol-3-yl

 951.

 3-fluoropropyl 5-isopropyl-4-methyl-4H- [1,2,4] triazol-3-yl

 952

 3-fluoropropyl 5-trifluoromethyl-4-methyl-4H- [1,2,4] triazol-3-yl

 953

 3-fluoropropyl [1,3,4] thiadiazol-2-yl

 954.

 3-fluoropropyl 5-methyl- [1,3,4] thiadiazol-2-yl

 955

 3-fluoropropyl 5-isopropyl- [1,3,4] thiadiazol-2-yl

 956.

 3-fluoropropyl 5-trifluoromethyl- [1,3,4] thiadiazol-2-yl

 957

 3-fluoropropyl 3-bromo-2-chloropyrid-5-yl

 958.

 3-fluoropropyl 2- (4-morpholino) -pyrid-5-yl

 959.

 3-fluoropropyl 2-phenoxypyrid-5-yl

 960

 3-fluoropropyl (2-isopropyl) -pyrimidin-5-yl

 961.

 3-fluoropropyl (5-isopropyl) -pyrimidin-2-yl

 962.

 3-fluoropropyl 8-quinolyl

 963

 3-fluoropropyl 5-isoquinolyl

 964

 3-fluoropropyl 2- (trifluoroacetyl) -1,2,3,4-tetrahydroisoquinolin-7-yl

 965

 3-fluoropropyl 5-chloro-3-methylbenzothiophene-2-yl

 Do not.

 R1 Ar

 966.

 3-fluoropropyl 3,4-dihydro-4-methyl-2H-benzo [b] [1,4] oxazinyl

 967.

 3-fluoropropyl benzothiazol-6-yl

 968.

 3-fluoropropyl benzo [2,1,3] oxadiazol-4-yl

 969.

 3-fluoropropyl 5-chlorobenzo [2,1,3] oxadiazol-4-yl

 970

 3-fluoropropyl 7-chlorobenzo [2,1,3] oxadiazol-4-yl

 971.

 3-fluoropropyl benzo [2,1,3] thiadiazol-4-yl

 972.

 3-fluoropropyl 6-chloroimidazo [2,1-b] thiazolyl

 973

 2-fluoroethyl 4-methylphenyl

 974

 2-fluoroethyl 4-ethylphenyl

 975

 2-fluoroethyl 4-propylphenyl

 976

 2-fluoroethyl 4-isopropylphenyl

 977

 2-fluoroethyl 4-sec-butylphenyl

 978.

 2-fluoroethyl 4-isobutylphenyl

 979

 2-fluoroethyl 4- (1,1-dimethylpropyl) -phenyl

 980

 2-fluoroethyl 4-vinylphenyl

 981.

 2-fluoroethyl 4-isopropenylphenyl

 982.

 2-fluoroethyl 4-fluorophenyl

 983

 2-fluoroethyl 4-chlorophenyl

 984.

 2-fluoroethyl 4-bromophenyl

 985.

 2-fluoroethyl 4- (fluoromethyl) phenyl

 986.

 2-fluoroethyl 3- (fluoromethyl) phenyl

 987.

 2-Fluoroethyl 2- (fluoromethyl) phenyl

 988

 2-fluoroethyl 4- (difluoromethyl) phenyl

 989.

 2-fluoroethyl 3- (difluoromethyl) phenyl

 990

 2-fluoroethyl 2- (difluoromethyl) phenyl

 991.

 2-fluoroethyl 4- (trifluoromethyl) phenyl

 992.

 2-fluoroethyl 3- (trifluoromethyl) phenyl

 993

 2-fluoroethyl 2- (trifluoromethyl) phenyl

 994.

 2-fluoroethyl 4- (1-fluoroethyl) -phenyl

 Do not.

 R1 Ar

 995

 2-fluoroethyl 4 - ((S) -1-fluoroethyl) -phenyl

 996.

 2-fluoroethyl 4 - ((R) -1-fluoroethyl) -phenyl

 997.

 2-fluoroethyl .4- (2-fluoroethyl) -phenyl

 998.

 2-fluoroethyl 4- (1,1-difluoroethyl) -phenyl

 999

 2-fluoroethyl 4- (2,2-difluoroethyl) -phenyl

 1000

 2-fluoroethyl 4- (2,2,2-trifluoroethyl) -phenyl

 1001

 2-fluoroethyl 4- (3-fluoropropyl) -phenyl

 1002

 2-fluoroethyl 4- (2-fluoropropyl) -phenyl

 1003

 2-fluoroethyl 4 - ((S) -2-fluoropropyl) -phenyl

 1004

 2-fluoroethyl 4 - ((R) -2-fluoropropyl) -phenyl

 1005

 2-fluoroethyl 4- (3,3-difluoropropyl) -phenyl

 1006

 2-fluoroethyl 4- (3,3,3-trifluoropropyl) -phenyl

 1007

 2-fluoroethyl 4- (1-fluoro-1-methylethyl) -phenyl

 1008

 2-fluoroethyl 4- (2-fluoro-1-methylethyl) -phenyl

 1009

 2-fluoroethyl 4 - ((S) -2-fluoro-1-methylethyl) -phenyl

 1010

 2-fluoroethyl 4 - ((R) -2-fluoro-1-methylethyl) -phenyl

 1011

 2-fluoroethyl 4- (2,2-difluoro-1-methylethyl) -phenyl

 1012

 2-fluoroethyl 4 - ((S) -2,2-difluoro-1-methylethyl) -phenyl

 1013

 2-fluoroethyl 4 - ((R) -2,2-difluoro-1-methylethyl) -phenyl

 1014

 2-Fluoroethyl 4- (2,2,2-trifluoro-1-methylethyl) -phenyl

 1015

 2-fluoroethyl 4 - ((S) -2,2,2-trifluoro-1-methylethyl) -phenyl

 1016

 2-fluoroethyl 4 - ((R) -2,2,2-trifluoro-1-methylethyl) -phenyl

 1017

 2-fluoroethyl 4- (2-fluoro-1-fluoromethylethyl) -phenyl

 1018

 2-fluoroethyl 4- (1-difluoromethyl-2,2-difluoroethyl) -phenyl

 1019

 2-fluoroethyl 4- (1,1-dimethyl-2-fluoroethyl) -phenyl

 1020

 2-fluoroethyl 4-methoxyphenyl

 1021

 2-fluoroethyl 4-ethoxyphenyl

 1022

 2-fluoroethyl 4-propoxyphenyl

 1023

 2-fluoroethyl 4-isopropoxyphenyl

 Do not.

 R1 Ar

 1024.

 2-fluoroethyl 4-butoxyphenyl

 1025

 2-fluoroethyl 4- (fluoromethoxy) -phenyl

 1026

 2-fluoroethyl 4- (difluoromethoxy) -phenyl

 1027

 2-fluoroethyl 4- (trifluoromethoxy) -phenyl

 1028

 2-fluoroethyl 3- (trifluoromethoxy) -phenyl

 1029

 2-fluoroethyl 4- (2-fluoroethoxy) -phenyl

 1030

 2-fluoroethyl 4- (2,2-difluoroethoxy) -phenyl

 1031

 2-fluoroethyl 4- (2,2,2-trifluoroethoxy) -phenyl

 1032

 2-Fluoroethyl 4- (1,1,2,2-tetrafluoroethoxy) -phenyl

 1033

 2-fluoroethyl 4-cyclopropylphenyl

 1034

 2-fluoroethyl 4-cyclobutylphenyl

 1035

 2-fluoroethyl 4-cyclopentylphenyl

 1036

 2-fluoroethyl 4- (2,2-difluorocyclopropyl) -phenyl

 1037

 2-fluoroethyl 3,4-difluorophenyl

 1038

 2-fluoroethyl 4-bromo-3-fluorophenyl

 1039

 2-fluoroethyl 4-bromo-2-fluorophenyl

 1040

 2-fluoroethyl 4-bromo-2,5-difluorophenyl

 1041

 2-fluoroethyl 2-fluoro-4-isopropylphenyl

 1042

 2-fluoroethyl 3-fluoro-4-isopropylphenyl

 1043

 2-fluoroethyl 4- (1-hydroxy-1-methylethyl) -phenyl

 1044

 2-fluoroethyl 4- (2-hydroxy-2-methylpropyl) -phenyl

 1045

 2-fluoroethyl 4-acetylphenyl

 1046

 2-fluoroethyl 4-carboxyphenyl

 1047

 2-fluoroethyl 4-cyanophenyl

 1048

 2-fluoroethyl 4-hydroxyphenyl

 1049

 2-fluoroethyl 4- (O-benzyl) -phenyl

 1050

 2-fluoroethyl 4- (2-methoxyethoxy) -phenyl

 1051

 2-fluoroethyl 4- (CH2-N (CH3) 2) -phenyl

 1052

 2-fluoroethyl 4- (NH-CO-NH2) -phenyl

 Do not.

 R1 Ar

 1053

 2-fluoroethyl 4- (methylsulfanyl) -phenyl

 1054

 2-fluoroethyl 4- (fluoromethylsulfanyl) -phenyl

 1055

 2-fluoroethyl 4- (difluoromethylsulfanyl) -phenyl

 1056

 2-fluoroethyl 4- (trifluoromethylsulfanyl) -phenyl

 1057

 2-fluoroethyl 4- (methylsulfonyl) -phenyl

 1058

 2-fluoroethyl 4- (N-methoxy-N-methyl-amino) -phenyl

 1059

 2-fluoroethyl 4- (methoxyamino) -phenyl

 1060

 2-fluoroethyl 4- (ethoxyamino) -phenyl

 1061

 2-fluoroethyl 4- (N-methylaminooxy) -phenyl

 1062

 2-fluoroethyl 4- (N, N-dimethylaminooxy) -phenyl

 1063

 2-fluoroethyl 4- (azetidin-1-yl) -phenyl

 1064

 2-fluoroethyl 4- (2-methylazetidin-1-yl) -phenyl

 1065

 2-fluoroethyl 4 - ((S) -2-methylazetidin-1-yl) -phenyl

 1066

 2-fluoroethyl 4 - ((R) -2-methylazetidin-1-yl) -phenyl

 1067

 2-fluoroethyl 4- (3-fluoroazetidin-1-yl) -phenyl

 1068

 2-fluoroethyl 4- (3-methoxyazetidin-1-yl) -phenyl

 1069

 2-fluoroethyl 4- (3-hydroxyazetidin-1-yl) -phenyl

 1070

 2-fluoroethyl 4- (pyrrolidin-1-yl) -phenyl

 1071

 2-fluoroethyl 4- (pyrrolidin-2-yl) -phenyl

 1072

 2-fluoroethyl 4 - ((S) -pyrrolidin-2-yl) -phenyl

 1073

 2-fluoroethyl 4 - ((R) -pyrrolidin-2-yl) -phenyl

 1074

 2-fluoroethyl 4- (pyrrolidin-3-yl) -phenyl

 1075

 2-fluoroethyl 4 - ((S) -pyrrolidin-3-yl) -phenyl

 1076

 2-fluoroethyl 4 - ((R) -pyrrolidin-3-yl) -phenyl

 1077

 2-Fluoroethyl 4- (2-fluoropyrrolidin-1-yl) -phenyl

 1078

 2-fluoroethyl 4 - ((S) -2-fluoropyrrolidin-1-yl) -phenyl

 1079

 2-fluoroethyl 4 - ((R) -2-fluoropyrrolidin-1-yl) -phenyl

 1080.

 2-fluoroethyl 4- (3-fluoropyrrolidin-1-yl) -phenyl

 1081

 2-fluoroethyl 4 - ((S) -3-fluoropyrrolidin-1-yl) -phenyl

 Do not.

 R1 Ar

 1082

 2-fluoroethyl 4 - ((R) -3-fluoropyrrolidin-1-yl) -phenyl

 1083

 2-fluoroethyl 4- (2,2-difluoropyrrolidin-1-yl) -phenyl

 1084

 2-fluoroethyl 4- (3,3-difluoropyrrolidin-1-yl) -phenyl

 1085

 2-fluoroethyl 4- (2-methylpyrrolidin-1-yl) -phenyl

 1086

 2-fluoroethyl 4 - ((S) -2-methylpyrrolidin-1-yl) -phenyl

 1087

 2-fluoroethyl 4 - ((R) -2-methylpyrrolidin-1-yl) -phenyl

 1088

 2-fluoroethyl 4- (3-methylpyrrolidin-1-yl) -phenyl

 1089

 2-fluoroethyl 4 - ((S) -3-methylpyrrolidin-1-yl) -phenyl

 1090

 2-fluoroethyl 4 - ((R) -3-methylpyrrolidin-1-yl) -phenyl

 1091

 2-fluoroethyl 4- (1-methylpyrrolidin-2-yl) -phenyl

 1092

 2-fluoroethyl 4 - ((S) -1-methylpyrrolidin-2-yl) -phenyl

 1093

 2-fluoroethyl 4 - ((R) -1-methylpyrrolidin-2-yl) -phenyl

 1094.

 2-fluoroethyl 4- (1-methylpyrrolidin-3-yl) -phenyl

 1095

 2-fluoroethyl 4 - ((S) -1-methylpyrrolidin-3-yl) -phenyl

 1096

 2-fluoroethyl 4 - ((R) -1-methylpyrrolidin-3-yl) -phenyl

 1097

 2-fluoroethyl 4- (2,2-dimethylpyrrolidin-1-yl) -phenyl

 1098.

 2-fluoroethyl 4- (3,3-dimethylpyrrolidin-1-yl) -phenyl

 1099

 2-fluoroethyl 4- (2-trifluoromethylpyrrolidin-1-yl) -phenyl

 1100

 2-fluoroethyl 4 - ((S) -2-trifluoromethylpyrrolidin-1-yl) -phenyl

 1101.

 2-fluoroethyl 4 - ((R) -2-trifluoromethylpyrrolidin-1-yl) -phenyl

 1102

 2-fluoroethyl 4- (3-trifluoromethylpyrrolidin-1-yl) -phenyl

 1103

 2-fluoroethyl 4 - ((S) -3-trifluoromethylpyrrolidin-1-yl) -phenyl

 1104.

 2-fluoroethyl 4 - ((R) -3-trifluoromethylpyrrolidin-1-yl) -phenyl

 1105

 2-fluoroethyl 4- (2-oxopyrrolidin-1-yl) -phenyl

 1106.

 2-fluoroethyl 4- (2-oxo-oxazolidin-3-yl) -phenyl

 1107.

 2-fluoroethyl 4- (piperidin-1-yl) -phenyl

 1108.

 2-fluoroethyl 4- (2-methylpiperidin-1-yl) -phenyl

 1109.

 2-fluoroethyl 4 - ((S) -2-methylpiperidin-1-yl) -phenyl

 1110

 2-fluoroethyl 4 - ((R) -2-methylpiperidin-1-yl) -phenyl

 Do not.

 R1 Ar

 1111

 2-fluoroethyl 4- (piperazin-1-yl) -phenyl

 1112

 2-fluoroethyl 4- (4-methylpiperazin-1-yl) -phenyl

 1113

 2-fluoroethyl 4- (morpholin-4-yl) -phenyl

 1114

 2-fluoroethyl 4- (thiomorpholin-4-yl) -phenyl

 1115

 2-fluoroethyl 4- (1-oxo-thiomorpholin-4-yl) -phenyl

 1116

 2-fluoroethyl 4- (1,1-dioxo-thiomorpholin-4-yl) -phenyl

 1117

 2-fluoroethyl 4- (pyrrol-1-yl) -phenyl

 1118

 2-fluoroethyl 4- (pyrrol-2-yl) -phenyl

 1119

 2-fluoroethyl 4- (pyrrol-3-yl) -phenyl

 1120

 2-fluoroethyl 4- (1-methylpyrrol-2-yl) -phenyl

 1121

 2-fluoroethyl 4- (1-methylpyrrol-3-yl) -phenyl

 1122

 2-fluoroethyl 4- (furan-2-yl) -phenyl

 1123

 2-fluoroethyl 4- (furan-3-yl) -phenyl

 1124

 2-fluoroethyl 4- (thiophene-2-yl) -phenyl

 1125

 2-fluoroethyl 4- (thiophene-3-yl) -phenyl

 1126

 2-fluoroethyl 4- (5-propylthien-2-yl) -phenyl

 1127

 2-fluoroethyl 4- (pyrazol-1-yl) -phenyl

 1128

 2-fluoroethyl 4- (pyrazol-3-yl) -phenyl

 1129

 2-fluoroethyl 4- (pyrazol-4-yl) -phenyl

 1130.

 2-fluoroethyl 4- (1-methyl-1H-pyrazol-4-yl) -phenyl

 1131

 2-Fluoroethyl 4- (1-ethyl-1H-pyrazol-4-yl) -phenyl

 1132

 2-fluoroethyl 4- (1-methyl-1H-pyrazol-5-yl) -phenyl

 1133

 2-fluoroethyl 4- (1H-imidazol-2-yl) -phenyl

 1134.

 2-fluoroethyl 4- (imidazol-1-yl) -phenyl

 1135

 2-fluoroethyl 4- (1-methylimidazol-2-yl) -phenyl

 1136

 2-fluoroethyl 4- (oxazol-2-yl) -phenyl

 1137

 2-fluoroethyl 4- (oxazol-4-yl) -phenyl

 1138

 2-fluoroethyl 4- (oxazol-5-yl) -phenyl

 1139

 2-fluoroethyl 4- (isoxazol-3-yl) -phenyl

 Do not.

 R1 Ar

 1140

 2-fluoroethyl 4- (isoxazol-4-yl) -phenyl

 1141

 2-fluoroethyl 4- (isoxazol-5-yl) -phenyl

 1142

 2-fluoroethyl 4 - ([1,2,3] -triazol-1-yl) -phenyl

 1143

 2-fluoroethyl 4 - ([1,2,4] -triazol-1-yl) -phenyl

 1144

 2-fluoroethyl 4 - ([1,2,3] -triazol-2-yl) -phenyl

 1145

 2-Fluoroethyl 4- (4H- [1,2,4] -triazol-3-yl) -phenyl

 1146.

 2-fluoroethyl 4 - ([1,2,4] -triazol-4-yl) -phenyl

 1147

 2-Fluoroethyl 4- (2H- [1,2,3] -triazol-4-yl) -phenyl

 1148

 2-Fluoroethyl 4- (4-methyl-4H- [1,2,4] -triazol-3-yl) -phenyl

 1149.

 2-Fluoroethyl 4- (2-methyl-2H- [1,2,3] -triazol-4-yl) -phenyl

 1150

 2-fluoroethyl 4 - ([1,3,4] -oxadiazol-2-yl) -phenyl

 1151

 2-fluoroethyl 4 - ([1,2,4] -oxadiazol-3-yl) -phenyl

 1152

 2-fluoroethyl 4 - ([1,2,4] -oxadiazol-5-yl) -phenyl

 1153

 2-fluoroethyl 4 - ([1,2,3] -oxadiazol-4-yl) -phenyl

 1154

 2-fluoroethyl 4 - ([1,2,3] -oxadiazol-5-yl) -phenyl

 1155

 2-fluoroethyl 4 - ([1,2,3] -thiadiazol-4-yl) -phenyl

 1156

 2-fluoroethyl 4- (1H-tetrazol-5-yl) -phenyl

 1157

 2-fluoroethyl 4- (tetrazol-1-yl) -phenyl

 1158

 2-Fluoroethyl 4- (2-methyl-2H-tetrazol-5-yl) -phenyl

 1159

 2-fluoroethyl 4- (1-methyl-1H-tetrazol-5-yl) -phenyl

 1160

 2-fluoroethyl 4-furazan-3-yl-phenyl

 1161

 2-fluoroethyl 4- (pyrid-2-yl) -phenyl

 1162.

 2-fluoroethyl 4- (pyrid-3-yl) -phenyl

 1163

 2-fluoroethyl 4- (pyrid-4-yl) -phenyl

 1164

 2-fluoroethyl 4- (pyrimidin-2-yl) -phenyl

 1165

 2-fluoroethyl 4- (pyrimidin-4-yl) -phenyl

 1166.

 2-fluoroethyl 4- (pyrimidin-5-yl) -phenyl

 1167.

 2-fluoroethyl 5-isopropylthiophene-2-yl

 1168.

 2-fluoroethyl 2-chlorothiophene-5-yl

 Do not.

 R1 Ar

 1169

 2-fluoroethyl 2,5-dichlorothiophene-4-yl

 1170

 2-fluoroethyl 2,3-dichlorothiophene-5-yl

 1171.

 2-fluoroethyl 2-chloro-3-nitrothiophene-5-yl

 1172

 2-fluoroethyl 2- (phenylsulfonyl) -thiophene-5-yl

 1173

 2-fluoroethyl 2- (pyridin-2-yl) thiophene-5-yl

 1174

 2-Fluoroethyl 2- (5- (trifluoromethyl) isoxazol-3-yl) -thiophene-5-yl

 1175

 2-Fluoroethyl 2- (2-methylthiazol-4-yl) -thiophene-5-yl

 1176

 2-fluoroethyl 1-methyl-1H-imidazol-4-yl

 1177

 2-Fluoroethyl 1,2-dimethyl-1H-imidazol-4-yl

 1178.

 2-fluoroethyl 3,5-dimethylisoxazol-4-yl

 1179

 2-fluoroethyl thiazol-2-yl

 1180

 2-fluoroethyl 4-methylthiazol-2-yl

 1181

 2-fluoroethyl 4-isopropylthiazol-2-yl

 1182.

 2-fluoroethyl 4-trifluoromethylthiazol-2-yl

 1183

 2-fluoroethyl 5-methylthiazol-2-yl

 1184.

 2-fluoroethyl 5-isopropylthiazol-2-yl

 1185

 2-fluoroethyl 5-trifluoromethylthiazol-2-yl

 1186.

 2-Fluoroethyl 2,4-dimethylthiazol-5-yl

 1187

 2-fluoroethyl 2-acetamido-4-methylthiazol-5-yl

 1188

 2-fluoroethyl 4H- [1,2,4] triazol-3-yl

 1189

 2-fluoroethyl 5-methyl-4H- [1,2,4] triazol-3-yl

 1190

 2-fluoroethyl 4-methyl-4H- [1,2,4] triazol-3-yl

 1191.

 2-fluoroethyl 5-isopropyl-4H- [1,2,4] triazol-3-yl

 1192

 2-fluoroethyl 5-trifluoromethyl-4H- [1,2,4] triazol-3-yl

 1193.

 2-Fluoroethyl 4,5-dimethyl-4H- [1,2,4] triazol-3-yl

 1194.

 2-fluoroethyl 5-isopropyl-4-methyl-4H- [1,2,4] triazol-3-yl

 1195

 2-fluoroethyl 5-trifluoromethyl-4-methyl-4H- [1,2,4] triazol-3-yl

 1196.

 2-fluoroethyl [1,3,4] thiadiazol-2-yl

 1197.

 2-fluoroethyl 5-methyl- [1,3,4] thiadiazol-2-yl

 Do not.

 R1 Ar

 1198.

 2-fluoroethyl 5-isopropyl- [1,3,4] thiadiazol-2-yl

 1199

 2-fluoroethyl 5-trifluoromethyl- [1,3,4] thiadiazol-2-yl

 1200

 2-fluoroethyl 3-bromo-2-chloropyrid-5-yl

 1201.

 2-fluoroethyl 2- (4-morpholino) -pyrid-5-yl

 1202.

 2-fluoroethyl 2-phenoxypyrid-5-yl

 1203

 2-fluoroethyl (2-isopropyl) -pyrimidin-5-yl

 1204.

 2-fluoroethyl (5-isopropyl) -pyrimidin-2-yl

 1205

 2-fluoroethyl 8-quinolyl

 1206.

 2-fluoroethyl 5-isoquinolyl

 1207

 2-fluoroethyl 2- (trifluoroacetyl) -1,2,3,4-tetrahydroisoquinolin-7-yl

 1208.

 2-fluoroethyl 5-chloro-3-methylbenzothiophene-2-yl

 1209.

 2-Fluoroethyl 3,4-dihydro-4-methyl-2H-benzo [b] [1,4] oxazinyl

 1210

 2-fluoroethyl benzothiazol-6-yl

 1211

 2-Fluoroethyl benzo [2,1,3] oxadiazol-4-yl

 1212

 2-fluoroethyl 5-chlorobenzo [2,1,3] oxadiazol-4-yl

 1213

 2-fluoroethyl 7-chlorobenzo [2,1,3] oxadiazol-4-yl

 1214

 2-fluoroethyl benzo [2,1,3] thiadiazol-4-yl

 1215

 2-fluoroethyl 6-chloroimidazo [2,1-b] thiazolyl

 1216

 cyclopropylmethyl 4-methylphenyl

 1217

 cyclopropylmethyl 4-ethylphenyl

 1218

 cyclopropylmethyl 4-propylphenyl

 1219

 cyclopropylmethyl 4-isopropylphenyl

 1220

 cyclopropylmethyl 4-sec-butylphenyl

 1221

 cyclopropylmethyl 4-isobutylphenyl

 1222

 cyclopropylmethyl 4- (1,1-dimethylpropyl) -phenyl

 1223

 cyclopropylmethyl 4-vinylphenyl

 1224

 cyclopropylmethyl 4-isopropenylphenyl

 1225

 cyclopropylmethyl 4-fluorophenyl

 1226

 cyclopropylmethyl 4-chlorophenyl

 Do not.

 R1 Ar

 1227

 cyclopropylmethyl 4-bromophenyl

 1228

 cyclopropylmethyl 4- (fluoromethyl) phenyl

 1229

 cyclopropylmethyl 3- (fluoromethyl) phenyl

 1230.

 cyclopropylmethyl 2- (fluoromethyl) phenyl

 1231

 cyclopropylmethyl 4- (difluoromethyl) phenyl

 1232

 cyclopropylmethyl 3- (difluoromethyl) phenyl

 1233

 cyclopropylmethyl 2- (difluoromethyl) phenyl

 1234

 cyclopropylmethyl 4- (trifluoromethyl) phenyl

 1235

 cyclopropylmethyl 3- (trifluoromethyl) phenyl

 1236.

 cyclopropylmethyl 2- (trifluoromethyl) phenyl

 1237

 cyclopropylmethyl 4- (1-fluoroethyl) -phenyl

 1238.

 cyclopropylmethyl 4 - ((S) -1-fluoroethyl) -phenyl

 1239.

 cyclopropylmethyl 4 - ((R) -1-fluoroethyl) -phenyl

 1240

 cyclopropylmethyl 4- (2-fluoroethyl) -phenyl

 1241

 cyclopropylmethyl 4- (1,1-difluoroethyl) -phenyl

 1242

 cyclopropylmethyl 4- (2,2-difluoroethyl) -phenyl

 1243

 cyclopropylmethyl 4- (2,2,2-trifluoroethyl) -phenyl

 1244

 cyclopropylmethyl 4- (3-fluoropropyl) -phenyl

 1245

 cyclopropylmethyl 4- (2-fluoropropyl) -phenyl

 1246

 cyclopropylmethyl 4 - ((S) -2-fluoropropyl) -phenyl

 1247

 cyclopropylmethyl 4 - ((R) -2-fluoropropyl) -phenyl

 1248

 cyclopropylmethyl 4- (3,3-difluoropropyl) -phenyl

 1249

 cyclopropylmethyl 4- (3,3,3-trifluoropropyl) -phenyl

 1250

 cyclopropylmethyl 4- (1-fluoro-1-methylethyl) -phenyl

 1251

 cyclopropylmethyl 4- (2-fluoro-1-methylethyl) -phenyl

 1252

 cyclopropylmethyl 4 - ((S) -2-fluoro-1-methylethyl) -phenyl

 1253

 cyclopropylmethyl 4 - ((R) -2-fluoro-1-methylethyl) -phenyl

 1254

 cyclopropylmethyl 4- (2,2-difluoro-1-methylethyl) -phenyl

 1255

 cyclopropylmethyl 4 - ((S) -2,2-difluoro-1-methylethyl) -phenyl

 Do not.

 R1 Ar

 1256

 cyclopropylmethyl 4 - ((R) -2,2-difluoro-1-methylethyl) -phenyl

 1257

 cyclopropylmethyl 4- (2,2,2-trifluoro-1-methylethyl) -phenyl

 1258

 cyclopropylmethyl 4 - ((S) -2,2,2-trifluoro-1-methylethyl) -phenyl

 1259

 cyclopropylmethyl 4 - ((R) -2,2,2-trifluoro-1-methylethyl) -phenyl

 1260

 cyclopropylmethyl 4- (2-fluoro-1-fluoromethylethyl) -phenyl

 1261

 cyclopropylmethyl 4- (1-difluoromethyl-2,2-difluoroethyl) -phenyl

 1262

 cyclopropylmethyl 4- (1,1-dimethyl-2-fluoroethyl) -phenyl

 1263

 cyclopropylmethyl 4-methoxyphenyl

 1264

 cyclopropylmethyl 4-ethoxyphenyl

 1265

 cyclopropylmethyl 4-propoxyphenyl

 1266

 cyclopropylmethyl 4-isopropoxyphenyl

 1267.

 cyclopropylmethyl 4-butoxyphenyl

 1268

 cyclopropylmethyl 4- (fluoromethoxy) -phenyl

 1269

 cyclopropylmethyl 4- (difluoromethoxy) -phenyl

 1270

 cyclopropylmethyl 4- (trifluoromethoxy) -phenyl

 1271

 cyclopropylmethyl 3- (trifluoromethoxy) -phenyl

 1272

 cyclopropylmethyl 4- (2-fluoroethoxy) -phenyl

 1273

 cyclopropylmethyl 4- (2,2-difluoroethoxy) -phenyl

 1274

 cyclopropylmethyl 4- (2,2,2-trifluoroethoxy) -phenyl

 1275

 cyclopropylmethyl 4- (1,1,2,2-tetrafluoroethoxy) -phenyl

 1276

 cyclopropylmethyl 4-cyclopropylphenyl

 1277

 cyclopropylmethyl 4-cyclobutylphenyl

 1278.

 cyclopropylmethyl 4-cyclopentylphenyl

 1279

 cyclopropylmethyl 4- (2,2-difluorocyclopropyl) -phenyl

 1280

 cyclopropylmethyl 3,4-difluorophenyl

 1281

 cyclopropylmethyl 4-bromo-3-fluorophenyl

 1282

 cyclopropylmethyl 4-bromo-2-fluorophenyl

 1283

 cyclopropylmethyl 4-bromo-2,5-difluorophenyl

 1284.

 cyclopropylmethyl 2-fluoro-4-isopropylphenyl

 Do not.

 R1 Ar

 1285

 cyclopropylmethyl 3-fluoro-4-isopropylphenyl

 1286

 cyclopropylmethyl 4- (1-hydroxy-1-methylethyl) -phenyl

 1287

 cyclopropylmethyl 4- (2-hydroxy-2-methylpropyl) -phenyl

 1288

 cyclopropylmethyl 4-acetylphenyl

 1289

 cyclopropylmethyl 4-carboxyphenyl

 1290

 cyclopropylmethyl 4-cyanophenyl

 1291

 cyclopropylmethyl 4-hydroxyphenyl

 1292

 cyclopropylmethyl 4- (O-benzyl) -phenyl

 1293.

 cyclopropylmethyl 4- (2-methoxyethoxy) -phenyl

 1294.

 cyclopropylmethyl 4- (CH2-N (CH3) 2) -phenyl

 1295

 cyclopropylmethyl 4- (NH-CO-NH2) -phenyl

 1296

 cyclopropylmethyl 4- (methylsulfanyl) -phenyl

 1297

 cyclopropylmethyl 4- (fluoromethylsulfanyl) -phenyl

 1298.

 cyclopropylmethyl 4- (difluoromethylsulfanyl) -phenyl

 1299

 cyclopropylmethyl 4- (trifluoromethylsulfanyl) -phenyl

 1300

 cyclopropylmethyl 4- (methylsulfonyl) -phenyl

 1301.

 cyclopropylmethyl 4- (N-methoxy-N-methyl-amino) -phenyl

 1302

 cyclopropylmethyl 4- (methoxyamino) -phenyl

 1303

 cyclopropylmethyl 4- (ethoxyamino) -phenyl

 1304

 cyclopropylmethyl 4- (N-methylaminooxy) -phenyl

 1305

 cyclopropylmethyl 4- (N, N-dimethylaminooxy) -phenyl

 1306.

 cyclopropylmethyl 4- (azetidin-1-yl) -phenyl

 1307

 cyclopropylmethyl 4- (2-methylazetidin-1-yl) -phenyl

 1308.

 cyclopropylmethyl 4 - ((S) -2-methylazetidin-1-yl) -phenyl

 1309.

 cyclopropylmethyl 4 - ((R) -2-methylazetidin-1-yl) -phenyl

 1310

 cyclopropylmethyl 4- (3-fluoroazetidin-1-yl) -phenyl

 1311

 cyclopropylmethyl 4- (3-methoxyazetidin-1-yl) -phenyl

 1312

 cyclopropylmethyl 4- (3-hydroxyazetidin-1-yl) -phenyl

 1313

 cyclopropylmethyl 4- (pyrrolidin-1-yl) -phenyl

 Do not.

 R1 Ar

 1314

 cyclopropylmethyl 4- (pyrrolidin-2-yl) -phenyl

 1315

 cyclopropylmethyl 4 - ((S) -pyrrolidin-2-yl) -phenyl

 1316

 cyclopropylmethyl 4 - ((R) -pyrrolidin-2-yl) -phenyl

 1317

 cyclopropylmethyl 4- (pyrrolidin-3-yl) -phenyl

 1318

 cyclopropylmethyl 4 - ((S) -pyrrolidin-3-yl) -phenyl

 1319

 cyclopropylmethyl 4 - ((R) -pyrrolidin-3-yl) -phenyl

 1320

 cyclopropylmethyl 4- (2-fluoropyrrolidin-1-yl) -phenyl

 1321

 cyclopropylmethyl 4 - ((S) -2-fluoropyrrolidin-1-yl) -phenyl

 1322

 cyclopropylmethyl 4 - ((R) -2-fluoropyrrolidin-1-yl) -phenyl

 1323

 cyclopropylmethyl 4- (3-fluoropyrrolidin-1-yl) -phenyl

 1324

 cyclopropylmethyl 4 - ((S) -3-fluoropyrrolidin-1-yl) -phenyl

 1325

 cyclopropylmethyl 4 - ((R) -3-fluoropyrrolidin-1-yl) -phenyl

 1326

 cyclopropylmethyl 4- (2,2-difluoropyrrolidin-1-yl) -phenyl

 1327

 cyclopropylmethyl 4- (3,3-difluoropyrrolidin-1-yl) -phenyl

 1328

 cyclopropylmethyl 4- (2-methylpyrrolidin-1-yl) -phenyl

 1329

 cyclopropylmethyl 4 - ((S) -2-methylpyrrolidin-1-yl) -phenyl

 1330

 cyclopropylmethyl 4 - ((R) -2-methylpyrrolidin-1-yl) -phenyl

 1331

 cyclopropylmethyl 4- (3-methylpyrrolidin-1-yl) -phenyl

 1332

 cyclopropylmethyl 4 - ((S) -3-methylpyrrolidin-1-yl) -phenyl

 1333

 cyclopropylmethyl 4 - ((R) -3-methylpyrrolidin-1-yl) -phenyl

 1334.

 cyclopropylmethyl 4- (1-methylpyrrolidin-2-yl) -phenyl

 1335

 cyclopropylmethyl 4 - ((S) -1-methylpyrrolidin-2-yl) -phenyl

 1336

 cyclopropylmethyl 4 - ((R) -1-methylpyrrolidin-2-yl) -phenyl

 1337

 cyclopropylmethyl 4- (1-methylpyrrolidin-3-yl) -phenyl

 1338

 cyclopropylmethyl 4 - ((S) -1-methylpyrrolidin-3-yl) -phenyl

 1339

 cyclopropylmethyl 4 - ((R) -1-methylpyrrolidin-3-yl) -phenyl

 1340

 cyclopropylmethyl 4- (2,2-dimethylpyrrolidin-1-yl) -phenyl

 1341

 cyclopropylmethyl 4- (3,3-dimethylpyrrolidin-1-yl) -phenyl

 1342

 cyclopropylmethyl 4- (2-trifluoromethylpyrrolidin-1-yl) -phenyl

 Do not.

 R1 Ar

 1343

 cyclopropylmethyl 4 - ((S) -2-trifluoromethylpyrrolidin-1-yl) -phenyl

 1344

 cyclopropylmethyl 4 - ((R) -2-trifluoromethylpyrrolidin-1-yl) -phenyl

 1345

 cyclopropylmethyl 4- (3-trifluoromethylpyrrolidin-1-yl) -phenyl

 1346

 cyclopropylmethyl 4 - ((S) -3-trifluoromethylpyrrolidin-1-yl) -phenyl

 1347

 cyclopropylmethyl 4 - ((R) -3-trifluoromethylpyrrolidin-1-yl) -phenyl

 1348

 cyclopropylmethyl 4- (2-oxopyrrolidin-1-yl) -phenyl

 1349

 cyclopropylmethyl 4- (2-oxo-oxazolidin-3-yl) -phenyl

 1350

 cyclopropylmethyl 4- (piperidin-1-yl) -phenyl

 1351

 cyclopropylmethyl 4- (2-methylpiperidin-1-yl) -phenyl

 1352

 cyclopropylmethyl 4 - ((S) -2-methylpiperidin-1-yl) -phenyl

 1353

 cyclopropylmethyl 4 - ((R) -2-methylpiperidin-1-yl) -phenyl

 1354

 cyclopropylmethyl 4- (piperazin-1-yl) -phenyl

 1355

 cyclopropylmethyl 4- (4-methylpiperazin-1-yl) -phenyl

 1356

 cyclopropylmethyl 4- (morpholin-4-yl) -phenyl

 1357

 cyclopropylmethyl 4- (thiomorpholin-4-yl) -phenyl

 1358

 cyclopropylmethyl 4- (1-oxo-thiomorpholin-4-yl) -phenyl

 1359

 cyclopropylmethyl 4- (1,1-dioxo-thiomorpholin-4-yl) -phenyl

 1360

 cyclopropylmethyl 4- (pyrrol-1-yl) -phenyl

 1361

 cyclopropylmethyl 4- (pyrrol-2-yl) -phenyl

 1362

 cyclopropylmethyl 4- (pyrrol-3-yl) -phenyl

 1363

 cyclopropylmethyl 4- (1-methylpyrrol-2-yl) -phenyl

 1364

 cyclopropylmethyl 4- (1-methylpyrrol-3-yl) -phenyl

 1365

 cyclopropylmethyl 4- (furan-2-yl) -phenyl

 1366

 cyclopropylmethyl 4- (furan-3-yl) -phenyl

 1367.

 cyclopropylmethyl 4- (thiophene-2-yl) -phenyl

 1368

 cyclopropylmethyl 4- (thiophene-3-yl) -phenyl

 1369

 cyclopropylmethyl 4- (5-propylthien-2-yl) -phenyl

 1370

 cyclopropylmethyl 4- (pyrazol-1-yl) -phenyl

 1371

 cyclopropylmethyl 4- (pyrazol-3-yl) -phenyl

 Do not.

 R1 Ar

 1372

 cyclopropylmethyl 4- (pyrazol-4-yl) -phenyl

 1373

 cyclopropylmethyl 4- (1-methyl-1H-pyrazol-4-yl) -phenyl

 1374

 cyclopropylmethyl 4- (1-ethyl-1H-pyrazol-4-yl) -phenyl

 1375

 cyclopropylmethyl 4- (1-methyl-1H-pyrazol-5-yl) -phenyl

 1376

 cyclopropylmethyl 4- (1H-imidazol-2-yl) -phenyl

 1377

 cyclopropylmethyl 4- (imidazol-1-yl) -phenyl

 1378

 cyclopropylmethyl 4- (1-methylimidazol-2-yl) -phenyl

 1379

 cyclopropylmethyl 4- (oxazol-2-yl) -phenyl

 1380

 cyclopropylmethyl 4- (oxazol-4-yl) -phenyl

 1381

 cyclopropylmethyl 4- (oxazol-5-yl) -phenyl

 1382

 cyclopropylmethyl 4- (isoxazol-3-yl) -phenyl

 1383

 cyclopropylmethyl 4- (isoxazol-4-yl) -phenyl

 1384

 cyclopropylmethyl 4- (isoxazol-5-yl) -phenyl

 1385

 cyclopropylmethyl 4 - ([1,2,3] -triazol-1-yl) -phenyl

 1386

 cyclopropylmethyl 4 - ([1,2,4] -triazol-1-yl) -phenyl

 1387

 cyclopropylmethyl 4 - ([1,2,3] -triazol-2-yl) -phenyl

 1388

 cyclopropylmethyl 4- (4H- [1,2,4] -triazol-3-yl) -phenyl

 1389

 cyclopropylmethyl 4 - ([1,2,4] -triazol-4-yl) -phenyl

 1390

 cyclopropylmethyl 4- (2H- [1,2,3] -triazol-4-yl) -phenyl

 1391

 cyclopropylmethyl 4- (4-methyl-4H- [1,2,4] -triazol-3-yl) -phenyl

 1392

 cyclopropylmethyl 4- (2-methyl-2H- [1,2,3] -triazol-4-yl) -phenyl

 1393

 cyclopropylmethyl 4 - ([1,3,4] -oxadiazol-2-yl) -phenyl

 1394

 cyclopropylmethyl 4 - ([1,2,4] -oxadiazol-3-yl) -phenyl

 1395

 cyclopropylmethyl 4 - ([1,2,4] -oxadiazol-5-yl) -phenyl

 1396

 cyclopropylmethyl 4 - ([1,2,3] -oxadiazol-4-yl) -phenyl

 1397

 cyclopropylmethyl 4 - ([1,2,3] -oxadiazol-5-yl) -phenyl

 1398

 cyclopropylmethyl 4 - ([1,2,3] -thiadiazol-4-yl) -phenyl

 1399

 cyclopropylmethyl 4- (1H-tetrazol-5-yl) -phenyl

 1400

 cyclopropylmethyl 4- (tetrazol-1-yl) -phenyl

 Do not.

 R1 Ar

 1401.

 cyclopropylmethyl 4- (2-methyl-2H-tetrazol-5-yl) -phenyl

 1402

 cyclopropylmethyl 4- (1-methyl-1H-tetrazol-5-yl) -phenyl

 1403

 cyclopropylmethyl 4-furazan-3-yl-phenyl

 1404

 cyclopropylmethyl 4- (pyrid-2-yl) -phenyl

 1405

 cyclopropylmethyl 4- (pyrid-3-yl) -phenyl

 1406.

 cyclopropylmethyl 4- (pyrid-4-yl) -phenyl

 1407

 cyclopropylmethyl 4- (pyrimidin-2-yl) -phenyl

 1408.

 cyclopropylmethyl 4- (pyrimidin-4-yl) -phenyl

 1409.

 cyclopropylmethyl 4- (pyrimidin-5-yl) -phenyl

 1410

 cyclopropylmethyl 5-isopropylthiophene-2-yl

 1411

 cyclopropylmethyl 2-chlorothiophene-5-yl

 1412

 cyclopropylmethyl 2,5-dichlorothiophene-4-yl

 1413

 cyclopropylmethyl 2,3-dichlorothiophene-5-yl

 1414

 cyclopropylmethyl 2-chloro-3-nitrothiophene-5-yl

 1415

 cyclopropylmethyl 2- (phenylsulfonyl) -thiophene-5-yl

 1416

 cyclopropylmethyl 2- (pyridin-2-yl) thiophene-5-yl

 1417

 cyclopropylmethyl 2- (5- (trifluoromethyl) isoxazol-3-yl) -thiophene-5-yl

 1418

 cyclopropylmethyl 2- (2-methylthiazol-4-yl) -thiophene-5-yl

 1419

 cyclopropylmethyl 1-methyl-1H-imidazol-4-yl

 1420

 cyclopropylmethyl 1,2-dimethyl-1H-imidazol-4-yl

 1421

 cyclopropylmethyl 3,5-dimethylisoxazol-4-yl

 1422

 cyclopropylmethyl thiazol-2-yl

 1423

 cyclopropylmethyl 4-methylthiazol-2-yl

 1424

 cyclopropylmethyl 4-isopropylthiazol-2-yl

 1425

 cyclopropylmethyl 4-trifluoromethylthiazol-2-yl

 1426

 cyclopropylmethyl 5-methylthiazol-2-yl

 1427

 cyclopropylmethyl 5-isopropylthiazol-2-yl

 1428

 cyclopropylmethyl 5-trifluoromethylthiazol-2-yl

 1429

 cyclopropylmethyl 2,4-dimethylthiazol-5-yl

 Do not.

 R1 Ar

 1430

 cyclopropylmethyl 2-acetamido-4-methylthiazol-5-yl

 1431

 cyclopropylmethyl 4H- [1,2,4] triazol-3-yl

 1432

 cyclopropylmethyl 5-methyl-4H- [1,2,4] triazol-3-yl

 1433

 cyclopropylmethyl 4-methyl-4H- [1,2,4] triazol-3-yl

 1434

 cyclopropylmethyl 5-isopropyl-4H- [1,2,4] triazol-3-yl

 1435

 cyclopropylmethyl 5-trifluoromethyl-4H- [1,2,4] triazol-3-yl

 1436

 cyclopropylmethyl 4,5-dimethyl-4H- [1,2,4] triazol-3-yl

 1437

 cyclopropylmethyl 5-isopropyl-4-methyl-4H- [1,2,4] triazol-3-yl

 1438

 cyclopropylmethyl 5-trifluoromethyl-4-methyl-4H- [1,2,4] triazol-3-yl

 1439

 cyclopropylmethyl [1,3,4] thiadiazol-2-yl

 1440

 cyclopropylmethyl 5-methyl- [1,3,4] thiadiazol-2-yl

 1441

 cyclopropylmethyl 5-isopropyl- [1,3,4] thiadiazol-2-yl

 1442

 cyclopropylmethyl 5-trifluoromethyl- [1,3,4] thiadiazol-2-yl

 1443

 cyclopropylmethyl 3-bromo-2-chloropyrid-5-yl

 1444

 cyclopropylmethyl 2- (4-morpholino) -pyrid-5-yl

 1445

 cyclopropylmethyl 2-phenoxypyrid-5-yl

 1446

 cyclopropylmethyl (2-isopropyl) -pyrimidin-5-yl

 1447

 cyclopropylmethyl (5-isopropyl) -pyrimidin-2-yl

 1448

 cyclopropylmethyl 8-quinolyl

 1449

 cyclopropylmethyl 5-isoquinolyl

 1450

 cyclopropylmethyl 2- (trifluoroacetyl) -1,2,3,4-tetrahydroisoquinolin-7-yl

 1451

 cyclopropylmethyl 5-chloro-3-methylbenzothiophene-2-yl

 1452

 cyclopropylmethyl 3,4-dihydro-4-methyl-2H-benzo [b] [1,4] oxazinyl

 1453

 cyclopropylmethyl benzothiazol-6-yl

 1454

 cyclopropylmethyl benzo [2,1,3] oxadiazol-4-yl

 1455

 cyclopropylmethyl 5-chlorobenzo [2,1,3] oxadiazol-4-yl

 1456

 cyclopropylmethyl 7-chlorobenzo [2,1,3] oxadiazol-4-yl

 1457

 cyclopropylmethyl benzo [2,1,3] thiadiazol-4-yl

 1458

 cyclopropylmethyl 6-chloroimidazo [2,1-b] thiazolyl

 Do not.

 R1 Ar

 1459

 4-methylphenyl allyl

 1460

 allyl 4-ethylphenyl

 1461

 4-propylphenyl allyl

 1462

 allyl 4-isopropylphenyl

 1463

 4-sec-butylphenyl allyl

 1464

 allyl 4-isobutylphenyl

 1465

 4- (1,1-dimethylpropyl) -phenyl allyl

 1466

 allyl 4-vinylphenyl

 1467.

 allyl 4-isopropenylphenyl

 1468

 4-fluorophenyl allyl

 1469

 4-chlorophenyl allyl

 1470

 4-bromophenyl allyl

 1471

 allyl 4- (fluoromethyl) phenyl

 1472

 allyl 3- (fluoromethyl) phenyl

 1473

 allyl 2- (fluoromethyl) phenyl

 1474

 4- (difluoromethyl) phenyl allyl

 1475

 allyl 3- (difluoromethyl) phenyl

 1476

 allyl 2- (difluoromethyl) phenyl

 1477

 4- (trifluoromethyl) phenyl allyl

 1478.

 allyl 3- (trifluoromethyl) phenyl

 1479

 2- (trifluoromethyl) phenyl allyl

 1480

 allyl 4- (1-fluoroethyl) -phenyl

 1481

 allyl 4 - ((S) -1-fluoroethyl) -phenyl

 1482

 allyl 4 - ((R) -1-fluoroethyl) -phenyl

 1483

 allyl 4- (2-fluoroethyl) -phenyl

 1484

 allyl 4- (1,1-difluoroethyl) -phenyl

 1485

 allyl 4- (2,2-difluoroethyl) -phenyl

 1486

 allyl 4- (2,2,2-trifluoroethyl) -phenyl

 1487

 4- (3-fluoropropyl) -phenyl allyl

 Do not.

 R1 Ar

 1488

 4- (2-fluoropropyl) -phenyl allyl

 1489

 allyl 4 - ((S) -2-fluoropropyl) -phenyl

 1490

 allyl 4 - ((R) -2-fluoropropyl) -phenyl

 1491

 4- (3,3-difluoropropyl) -phenyl allyl

 1492

 allyl 4- (3,3,3-trifluoropropyl) -phenyl

 1493

 4- (1-fluoro-1-methylethyl) -phenyl allyl

 1494.

 4- (2-fluoro-1-methylethyl) -phenyl allyl

 1495

 allyl 4 - ((S) -2-fluoro-1-methylethyl) -phenyl

 1496

 allyl 4 - ((R) -2-fluoro-1-methylethyl) -phenyl

 1497

 4- (2,2-difluoro-1-methylethyl) -phenyl allyl

 1498

 allyl 4 - ((S) -2,2-difluoro-1-methylethyl) -phenyl

 1499

 allyl 4 - ((R) -2,2-difluoro-1-methylethyl) -phenyl

 1500

 allyl 4- (2,2,2-trifluoro-1-methylethyl) -phenyl

 1501

 allyl 4 - ((S) -2,2,2-trifluoro-1-methylethyl) -phenyl

 1502

 allyl 4 - ((R) -2,2,2-trifluoro-1-methylethyl) -phenyl

 1503

 allyl 4- (2-fluoro-1-fluoromethylethyl) -phenyl

 1504

 allyl 4- (1-difluoromethyl-2,2-difluoroethyl) -phenyl

 1505

 4- (1,1-dimethyl-2-fluoroethyl) -phenyl allyl

 1506

 4-methoxyphenyl allyl

 1507

 allyl 4-ethoxyphenyl

 1508

 4-propoxyphenyl allyl

 1509

 allyl 4-isopropoxyphenyl

 1510

 4-butoxyphenyl allyl

 1511

 allyl 4- (fluoromethoxy) -phenyl

 1512

 4- (difluoromethoxy) -phenyl allyl

 1513

 4- (trifluoromethoxy) -phenyl allyl

 1514

 allyl 3- (trifluoromethoxy) -phenyl

 1515

 4- (2-fluoroethoxy) -phenyl allyl

 1516

 4- (2,2-difluoroethoxy) -phenyl allyl

 Do not.

 R1 Ar

 1517

 Allyl 4- (2,2,2-trifluoroethoxy) -phenyl

 1518

 allyl 4- (1,1,2,2-tetrafluoroethoxy) -phenyl

 1519

 4-cyclopropylphenyl allyl

 1520

 4-cyclobutylphenyl allyl

 1521

 4-cyclopentylphenyl allyl

 1522

 allyl 4- (2,2-difluorocyclopropyl) -phenyl

 1523

 3,4-difluorophenyl allyl

 1524

 allyl 4-bromo-3-fluorophenyl

 1525

 allyl 4-bromo-2-fluorophenyl

 1526

 allyl 4-bromo-2,5-difluorophenyl

 1527

 allyl 2-fluoro-4-isopropylphenyl

 1528

 allyl 3-fluoro-4-isopropylphenyl

 1529

 4- (1-hydroxy-1-methylethyl) -phenyl allyl

 1530

 4- (2-hydroxy-2-methylpropyl) -phenyl allyl

 1531

 allyl 4-acetylphenyl

 1532

 4-carboxyphenyl allyl

 1533

 4-cyanophenyl allyl

 1534

 4-hydroxyphenyl allyl

 1535

 4- (O-benzyl) -phenyl allyl

 1536

 4- (2-methoxyethoxy) -phenyl allyl

 1537

 4- (CH2-N (CH3) 2) -phenyl allyl

 1538

 allyl 4- (NH-CO-NH2) -phenyl

 1539

 4- (methylsulfanyl) -phenyl allyl

 1540

 allyl 4- (fluoromethylsulfanyl) -phenyl

 1541

 allyl 4- (difluoromethylsulfanyl) -phenyl

 1542

 4- (trifluoromethylsulfanyl) -phenyl allyl

 1543

 4- (methylsulfonyl) -phenyl allyl

 1544

 4- (N-methoxy-N-methyl-amino) -phenyl allyl

 1545

 allyl 4- (methoxyamino) -phenyl

 Do not.

 R1 Ar

 1546

 allyl 4- (ethoxyamino) -phenyl

 1547

 4- (N-methylaminooxy) -phenyl allyl

 1548

 4- (N, N-dimethylaminooxy) -phenyl allyl

 1549

 allyl 4- (azetidin-1-yl) -phenyl

 1550

 allyl 4- (2-methylazetidin-1-yl) -phenyl

 1551

 allyl 4 - ((S) -2-methylazetidin-1-yl) -phenyl

 1552

 allyl 4 - ((R) -2-methylazetidin-1-yl) -phenyl

 1553

 allyl 4- (3-fluoroazetidin-1-yl) -phenyl

 1554

 4- (3-methoxyazetidin-1-yl) -phenyl allyl

 1555

 4- (3-hydroxyazetidin-1-yl) -phenyl allyl

 1556

 4- (pyrrolidin-1-yl) -phenyl allyl

 1557

 4- (pyrrolidin-2-yl) -phenyl allyl

 1558

 allyl 4 - ((S) -pirro) idin-2-yl) -phenyl

 1559

 allyl 4 - ((R) -pyrrolidin-2-yl) -phenyl

 1560

 4- (pyrrolidin-3-yl) -phenyl allyl

 1561

 allyl 4 - ((S) -pyrrolidin-3-yl) -phenyl

 1562

 allyl 4 - ((R) -pyrrolidin-3-yl) -phenyl

 1563

 4- (2-fluoropyrrolidin-1-yl) -phenyl allyl

 1564

 allyl 4 - ((S) -2-fluoropyrrolidin-1-yl) -phenyl

 1565

 allyl 4 - ((R) -2-fluoropyrrolidin-1-yl) -phenyl

 1566

 4- (3-fluoropyrrolidin-1-yl) -phenyl allyl

 1567

 allyl 4 - ((S) -3-fluoropyrrolidin-1-yl) -phenyl

 1568

 allyl 4 - ((R) -3-fluoropyrrolidin-1-yl) -phenyl

 1569

 4- (2,2-difluoropyrrolidin-1-yl) -phenyl allyl

 1570

 4- (3,3-difluoropyrrolidin-1-yl) -phenyl allyl

 1571

 4- (2-methylpyrrolidin-1-yl) -phenyl allyl

 1572

 allyl 4 - ((S) -2-methylpyrrolidin-1-yl) -phenyl

 1573

 allyl 4 - ((R) -2-methylpyrrolidin-1-yl) -phenyl

 1574

 4- (3-methylpyrrolidin-1-yl) -phenyl allyl

 Do not.

 R1 Ar

 1575

 allyl 4 - ((S) -3-methylpyrrolidin-1-yl) -phenyl

 1576

 allyl 4 - ((R) -3-methylpyrrolidin-1-yl) -phenyl

 1577

 4- (1-methylpyrrolidin-2-yl) -phenyl allyl

 1578

 allyl 4 - ((S) -1-methylpyrrolidin-2-yl) -phenyl

 1579

 allyl 4 - ((R) -1-methylpyrrolidin-2-yl) -phenyl

 1580

 4- (1-methylpyrrolidin-3-yl) -phenyl allyl

 1581

 allyl 4 - ((S) -1-metithpyrrolidin-3-yl) -phenyl

 1582

 allyl 4 - ((R) -1-methylpyrrolidin-3-yl) -phenyl

 1583

 4- (2,2-dimethylpyrrolidin-1-yl) -phenyl allyl

 1584

 4- (3,3-dimethylpyrrolidin-1-yl) -phenyl allyl

 1585

 4- (2-trifluoromethylpyrrolidin-1-yl) -phenyl allyl

 1586

 allyl 4 - ((S) -2-trifluoromethylpyrrolidin-1-yl) -phenyl

 1587

 allyl 4 - ((R) -2-trifluoromethylpyrrolidin-1-yl) -phenyl

 1588

 4- (3-trifluoromethylpyrrolidin-1-yl) -phenyl allyl

 1589

 allyl 4 - ((S) -3-trifluoromethylpyrrolidin-1-yl) -phenyl

 1590

 allyl 4 - ((R) -3-trifluoromethylpyrrolidin-1-yl) -phenyl

 1591

 4- (2-oxopyrrolidin-1-yl) -phenyl allyl

 1592

 4- (2-oxo-oxazolidin-3-yl) -phenyl allyl

 1593

 4- (piperidin-1-yl) -phenyl allyl

 1594.

 4- (2-methylpiperidin-1-yl) -phenyl allyl

 1595

 allyl 4 - ((S) -2-methylpiperidin-1-yl) -phenyl

 1596

 allyl 4 - ((R) -2-methylpiperidin-1-yl) -phenyl

 1597

 allyl 4- (piperazin-1-yl) -phenyl

 1598

 4- (4-methylpiperazin-1-yl) -phenyl allyl

 1599

 allyl 4- (morpholin-4-yl) -phenyl

 1600.

 allyl 4- (thiomorpholin-4-yl) -phenyl

 1601

 4- (1-oxo-thiomorpholin-4-yl) -phenyl allyl

 1602

 allyl 4- (1,1-dioxo-thiomorpholin-4-yl) -phenyl

 1603

 4- (pyrrol-1-yl) -phenyl allyl

 Do not.

 R1 Ar

 1604

 4- (pyrrol-2-yl) -phenyl allyl

 1605

 4- (pyrrol-3-yl) -phenyl allyl

 1606

 4- (1-methylpyrrol-2-yl) -phenyl allyl

 1607

 4- (1-methylpyrrol-3-yl) -phenyl allyl

 1608

 4- (furan-2-yl) -phenyl allyl

 1609

 4- (furan-3-yl) -phenyl allyl

 1610

 4- (thiophene-2-yl) -phenyl allyl

 1611

 4- (thiophene-3-yl) -phenyl allyl

 1612

 4- (5-propylthien-2-yl) -phenyl allyl

 1613

 allyl 4- (pyrazol-1-yl) -phenyl

 1614

 allyl 4- (pyrazol-3-yl) -phenyl

 1615

 4- (pyrazol-4-yl) -phenyl allyl

 1616

 4- (1-methyl-1H-pyrazol-4-yl) -phenyl allyl

 1617

 4- (1-ethyl-1H-pyrazol-4-yl) -phenyl allyl

 1618

 4- (1-methyl-1H-pyrazol-5-yl) -phenyl allyl

 1619.

 4- (1 H -imidazol-2-yl) -phenyl allyl

 1620

 4- (imidazol-1-yl) -phenyl allyl

 1621

 4- (1-methylimidazol-2-yl) -phenyl allyl

 1622

 4- (oxazol-2-yl) -phenyl allyl

 1623

 4- (oxazol-4-yl) -phenyl allyl

 1624

 4- (oxazol-5-yl) -phenyl allyl

 1625

 4- (isoxazol-3-yl) -phenyl allyl

 1626

 4- (isoxazol-4-yl) -phenyl allyl

 1627

 4- (isoxazol-5-yl) -phenyl allyl

 1628

 allyl 4 - ([1,2,3] -triazol-1-yl) -phenyl

 1629

 allyl 4 - ([1,2,4] -triazol-1-yl) -phenyl

 1630

 allyl 4 - ([1,2,3] -triazol-2-yl) -phenyl

 1631

 4- (4H- [1,2,4] -triazol-3-yl) -pheriyl allyl

 1632

 allyl 4 - ([1,2,4] -triazol-4-yl) -phenyl

 Do not.

 R1 Ar

 1633

 4- (2H- [1,2,3] -triazol-4-yl) -phenyl allyl

 1634.

 4- (4-methyl-4H- [1,2,4] -triazol-3-yl) -phenyl allyl

 1635

 4- (2-methyl-2H- [1,2,3] -triazol-4-yl) -phenyl allyl

 1636

 allyl 4 - ([1,3,4] -oxadiazol-2-yl) -phenyl

 1637

 allyl 4 - ([1,2,4] -oxadiazol-3-yl) -phenyl

 1638

 allyl 4 - ([1,2,4] -oxadiazol-5-yl) -phenyl

 1639

 allyl 4 - ([1,2,3] -oxadiazol-4-yl) -phenyl

 1640

 allyl 4 - ([1,2,3] -oxadiazol-5-yl) -phenyl

 1641

 allyl 4 - ([1,2,3] -thiadiazol-4-yl) -phenyl

 1642

 4- (1H-tetrazol-5-yl) -phenyl allyl

 1643

 4- (tetrazol-1-yl) -phenyl allyl

 1644

 4- (2-methyl-2H-tetrazol-5-yl) -phenyl allyl

 1645

 4- (1-methyl-1H-tetrazol-5-yl) -phenyl allyl

 1646

 allyl 4-furazan-3-yl-phenyl

 1647

 4- (pyrid-2-yl) -phenyl allyl

 1648

 4- (pyrid-3-yl) -phenyl allyl

 1649

 4- (pyrid-4-yl) -phenyl allyl

 1650

 allyl 4- (pyrimidin-2-yl) -phenyl

 1651

 4- (pyrimidin-4-yl) -phenyl allyl

 1652

 4- (pyrimidin-5-yl) -phenyl allyl

 1653

 allyl 5-isopropylthiophene-2-yl

 1654

 allyl 2-chlorothiophene-5-yl

 1655

 allyl 2,5-dichlorothiophene-4-yl

 1656

 allyl 2,3-dichlorothiophene-5-yl

 1657

 allyl 2-chloro-3-nitrothiophene-5-yl

 1658

 allyl 2- (phenylsulfonyl) -thiophene-5-yl

 1659

 allyl 2- (pyridin-2-yl) thiophene-5-yl

 1660

 2- (5- (trifluoromethyl) isoxazol-3-yl) -thiophene-5-yl allyl

 1661

 2- (2-methylthiazol-4-yl) -thiophene-5-yl allyl

 Do not.

 R1 Ar

 1662.

 1-methyl-1H-imidazol-4-yl allyl

 1663

 1,2-dimethyl-1H-imidazol-4-yl allyl

 1664

 3,5-dimethylisoxazol-4-yl allyl

 1665

 allyl thiazol-2-yl

 1666.

 allyl 4-methylthiazol-2-yl

 1667.

 allyl 4-isopropylthiazol-2-yl

 1668.

 allyl 4-trifluoromethylthiazol-2-yl

 1669

 allyl 5-methylthiazol-2-yl

 1670

 allyl 5-isopropylthiazol-2-yl

 1671

 allyl 5-trifluoromethylthiazol-2-yl

 1672

 allyl 2,4-dimethylthiazol-5-yl

 1673

 allyl 2-acetamido-4-methylthiazol-5-yl

 1674

 allyl 4H- [1,2,4] triazol-3-yl

 1675

 5-methyl-4H- [1,2,4] triazol-3-yl allyl

 1676

 4-methyl-4H- [1,2,4] triazol-3-yl allyl

 1677

 allyl 5-isopropyl-4H- [1,2,4] triazol-3-yl

 1678.

 allyl 5-trifluoromethyl-4H- [1,2,4] triazol-3-yl

 1679

 allyl 4,5-dimethyl-4H- [1,2,4] triazol-3-yl

 1680

 allyl 5-isopropyl-4-methyl-4H- [1,2,4] triazol-3-yl

 1681.

 5-trifluoromethyl-4-methyl-4H- [1,2,4] triazol-3-yl allyl

 1682.

 allyl [1,3,4] thiadiazol-2-yl

 1683

 allyl 5-methyl- [1,3,4] thiadiazol-2-yl

 1684.

 allyl 5-isopropyl- [1,3,4] thiadiazol-2-yl

 1685

 5-trifluoromethyl- [1,3,4] thiadiazol-2-yl allyl

 1686

 allyl 3-bromo-2-chloropyrid-5-yl

 1687

 allyl 2- (4-morpholino) -pyrid-5-yl

 1688

 allyl 2-phenoxypyrid-5-yl

 1689

 allyl (2-isopropyl) -pyrimidin-5-yl

 1690

 allyl (5-isopropyl) -pyrimidin-2-yl

 Do not.

 R1 Ar

 1691.

 8-quinolyl allyl

 1692

 5-isoquinolyl allyl

 1693.

 allyl 2- (trifluoroacetyl) -1,2,3,4-tetrahydroisoquinolin-7-yl

 1694.

 allyl 5-chloro-3-methylbenzothiophene-2-yl

 1695

 3,4-dihydro-4-methyl-2H-benzo [b] [1,4] oxazinyl allyl

 1696.

 allyl benzothiazol-6-yl

 1697.

 allyl benzo [2,1,3] oxadiazol-4-yl

 1698.

 allyl 5-chlorobenzo [2,1,3] oxadiazol-4-yl

 1699

 allyl 7-chlorobenzo [2,1,3] oxadiazol-4-yl

 1700

 allyl benzo [2,1,3] thiadiazol-4-yl

 1701

 6-chloroimidazo [2,1-b] thiazolyl allyl

 1702

 H 4- (trifluoromethoxy) -phenyl

 1703

 H 3- (trifluoromethoxy) -phenyl

 1704

 H 4-cyanophenyl

 1705

 H 4-methylphenyl

 1706

 H 4-ethylphenyl

 1707

 H 4-propylphenyl

 1708

 H 4-methoxyphenyl

 1709

 H 4-fluorophenyl

 1710

 H 4-chlorophenyl

 1711

 H 4-bromophenyl

 1712

 H 3- (trifluoromethyl) phenyl

 1713

 H 4- (trifluoromethyl) phenyl

 1714

 H 2- (trifluoromethyl) phenyl

 1715

 H 3,4-difluorophenyl

 1716

 H 4-bromo-3-fluorophenyl

 1717

 H 4-bromo-2-fluorophenyl

 1718

 H 4-bromo-2,5-difluorophenyl

 1719

 H 2-fluoro-4-isopropylphenyl

 Do not.

 R1 Ar

 1720

 H 4-hydroxyphenyl

 1721

 H 4-Isopropylphenyl

 1722

 H 4-sec-butylphenyl

 1723

 H 4-isobutylphenyl

 1724

 H 4- (1,1-dimethylpropyl) -phenyl

 1725

 H 4-vinylphenyl

 1726

 H 4-isopropenylphenyl

 1727

 H 4- (fluoromethyl) phenyl

 1728

 H 3- (fluoromethyl) phenyl

 1729

 H 2- (fluoromethyl) phenyl

 1730

 H 4- (difluoromethyl) phenyl

 1731

 H 3- (difluoromethyl) phenyl

 1732

 H 2- (difluoromethyl) phenyl

 1733

 H 4- (1-fluoroethyl) -phenyl

 1734

 H 4 - ((S) -1-fluoroethyl) -phenyl

 1735

 H 4 - ((R) -1-fluoroethyl) -phenyl

 1736

 H 4- (2-fluoroethyl) -phenyl

 1737

 H 4- (1,1-difluoroethyl) -phenyl

 1738

 H 4- (2,2-Difluoroethyl) -phenyl

 1739

 H 4- (2,2,2-trifluoroethyl) -phenyl

 1740

 H 4- (3-fluoropropyl) -phenyl

 1741

 H 4- (2-fluoropropyl) -phenyl

 1742

 H 4 - ((S) -2-fluoropropyl) -phenyl

 1743

 H 4 - ((R) -2-fluoropropyl) -phenyl

 1744

 H 4- (3,3-Difluoropropyl) -phenyl

 1745

 H 4- (3,3,3-trifluoropropyl) -phenyl

 1746

 H 4- (1-Fluoro-1-methylethyl) -phenyl

 1747

 H 4- (2-Fluoro-1-methylethyl) -phenyl

 1748

 H 4 - ((S) -2-fluoro-1-methylethyl) -phenyl

 Do not.

 R1 Ar

 1749

 H 4 - ((R) -2-fluoro-1-methylethyl) -phenyl

 1750

 H 4- (2,2-Difluoro-1-methylethyl) -phenyl

 1751

 H 4 - ((S) -2,2-difluoro-1-methylethyl) -phenyl

 1752

 H 4 - ((R) -2,2-difluoro-1-methylethyl) -phenyl

 1753

 H 4- (2,2,2-trifluoro-1-methylethyl) -phenyl

 1754

 H 4 - ((S) -2,2,2-trifluoro-1-methylethyl) -phenyl

 1755

 H 4 - ((R) -2,2,2-trifluoro-1-methylethyl) -phenyl

 1756

 H 4- (2-Fluoro-1-fluoromethylethyl) -phenyl

 1757

 H 4- (1-difluoromethyl-2,2-difluoroethyl) -phenyl

 1758

 H 4- (1,1-dimethyl-2-fluoroethyl) -phenyl

 1759

 H 4-ethoxyphenyl

 1760

 H 4-Propoxyphenyl

 1761

 H 4-isopropoxyphenyl

 1762

 H 4-Butoxyphenyl

 1763

 H 4- (fluoromethoxy) -phenyl

 1764

 H 4- (difluoromethoxy) -phenyl

 1765

 H 4- (2-Fluoroethoxy) -phenyl

 1766

 H 4- (2,2-Difluoroethoxy) -phenyl

 1767

 H 4- (2,2,2-trifluoroethoxy) -phenyl

 1768

 H 4- (1,1,2,2-tetrafluoroethoxy) -phenyl

 1769

 H 4-cyclopropylphenyl

 1770

 H 4-cyclobutylphenyl

 1771

 H 4-cyclopentylphenyl

 1772

 H 4- (2,2-Difluorocyclopropyl) -phenyl

 1773

 H 3-fluoro-4-isopropylphenyl

 1774

 H 4- (1-hydroxy-1-methylethyl) -phenyl

 1775

 H 4- (2-hydroxy-2-methylpropyl) -phenyl

 1776

 H 4-acetylphenyl

 1777

 H 4-carboxyphenyl

 Do not.

 R1 Ar

 1778

 H 4- (O-benzyl) -phenyl

 1779

 H 4- (2-Methoxyethoxy) -phenyl

 1780

 H 4- (CH2-N (CH3) 2) -phenyl

 1781

 H 4- (NH-CO-NH2) -phenyl

 1782

 H 4- (methylsulfanyl) -phenyl

 1783

 H 4- (fluoromethylsulfanyl) -phenyl

 1784

 H 4- (difluoromethylsulfanyl) -phenyl

 1785

 H 4- (trifluoromethylsulfanyl) -phenyl

 1786

 H 4- (methylsulfonyl) -phenyl

 1787

 H 4- (N-Methoxy-N-methyl-amino) -phenyl

 1788

 H 4- (methoxyamino) -phenyl

 1789

 H 4- (ethoxyamine) -phenyl

 1790

 H 4- (N-Methylaminooxy) -phenyl

 1791

 H 4- (N, N-dimethylaminooxy) -phenyl

 1792

 H 4- (azetidin-1-yl) -phenyl

 1793

 H 4- (2-Methylazetidin-1-yl) -phenyl

 1794

 H 4 - ((S) -2-methylazetidin-1-yl) -phenyl

 1795

 H 4 - ((R) -2-methylazetidin-1-yl) -phenyl

 1796

 H 4- (3-Fluoroazetidin-1-yl) -phenyl

 1797

 H 4- (3-Methoxyazetidin-1-yl) -phenyl

 1798

 H 4- (3-hydroxyazetidin-1-yl) -phenyl

 1799

 H 4- (pyrrolidin-1-yl) -phenyl

 1800

 H 4- (pyrrolidin-2-yl) -phenyl

 1801

 H 4 - ((S) -pyrrolidin-2-yl) -phenyl

 1802

 H 4 - ((R) -pyrrolidin-2-yl) -phenyl

 1803

 H 4- (pyrrolidin-3-yl) -phenyl

 1804

 H 4 - ((S) -pyrrolidin-3-yl) -phenyl

 1805

 H 4 - ((R) -pyrrolidin-3-yl) -phenyl

 1806

 H 4- (2-fluoropyrrolidin-1-yl) -phenyl

 Do not.

 R1 Ar

 1807

 H 4 - ((S) -2-fluoropyrrolidin-1-yl) -phenyl

 1808

 H 4 - ((R) -2-fluoropyrrolidin-1-yl) -phenyl

 1809

 H 4- (3-fluoropyrrolidin-1-yl) -phenyl

 1810

 H 4 - ((S) -3-fluoropyrrolidin-1-yl) -phenyl

 1811

 H 4 - ((R) -3-fluoropyrrolidin-1-yl) -phenyl

 1812

 H 4- (2,2-Difluoropyrrolidin-1-yl) -phenyl

 1813

 H 4- (3,3-Difluoropyrrolidin-1-yl) -phenyl

 1814

 H 4- (2-methylpyrrolidin-1-yl) -phenyl

 1815

 H 4 - ((S) -2-methylpyrrolidin-1-yl) -phenyl

 1816

 H 4 - ((R) -2-methylpyrrolidin-1-yl) -phenyl

 1817

 H 4- (3-methylpyrrolidin-1-yl) -phenyl

 1818

 H 4 - ((S) -3-methylpyrrolidin-1-yl) -phenyl

 1819

 H 4 - ((R) -3-methylpyrrolidin-1-yl) -phenyl

 1820

 H 4- (1-methylpyrrolidin-2-yl) -phenyl

 1821

 H 4 - ((S) -1-methylpyrrolidin-2-yl) -phenyl

 1822

 H 4 - ((R) -1-methylpyrrolidin-2-yl) -phenyl

 1823

 H 4- (1-methylpyrrolidin-3-yl) -phenyl

 1824

 H 4 - ((S) -1-methylpyrrolidin-3-yl) -phenyl

 1825

 H 4 - ((R) -1-methylpyrrolidin-3-yl) -phenyl

 1826

 H 4- (2,2-dimethylpyrrolidin-1-yl) -phenyl

 1827

 H 4- (3,3-dimethylpyrrolidin-1-yl) -phenyl

 1828

 H 4- (2-Trifluoromethylpyrrolidin-1-yl) -phenyl

 1829

 H 4 - ((S) -2-trifluoromethylpyrrolidin-1-yl) -phenyl

 1830

 H 4 - ((R) -2-trifluoromethylpyrrolidin-1-yl) -phenyl

 1831

 H 4- (3-Trifluoromethylpyrrolidin-1-yl) -phenyl

 1832

 H 4 - ((S) -3-trifluoromethylpyrrolidin-1-yl) -phenyl

 1833

 H 4 - ((R) -3-trifluoromethylpyrrolidin-1-yl) -phenyl

 1834

 H 4- (2-oxopyrrolidin-1-yl) -phenyl

 1835

 H 4- (2-oxo-oxazolidin-3-yl) -phenyl

 Do not.

 R1 Ar

 1836

 H 4- (piperidin-1-yl) -phenyl

 1837

 H 4- (2-methylpiperidin-1-yl) -phenyl

 1838

 H 4 - ((S) -2-methylpiperidin-1-yl) -phenyl

 1839

 H 4 - ((R) -2-methylpiperidin-1-yl) -phenyl

 1840

 H 4- (piperazin-1-yl) -phenyl

 1841

 H 4- (4-methylpiperazin-1-yl) -phenyl

 1842

 H 4- (morpholin-4-yl) -phenyl

 1843

 H 4- (thiomorpholin-4-yl) -phenyl

 1844

 H 4- (1-oxo-thiomorpholin-4-yl) -phenyl

 1845

 H 4- (1,1-dioxo-thiomorpholin-4-yl) -phenyl

 1846

 H 4- (pyrrol-1-yl) -phenyl

 1847

 H 4- (pyrrol-2-yl) -phenyl

 1848

 H 4- (pyrrol-3-yl) -phenyl

 1849

 H 4- (1-methylpyrrol-2-yl) -phenyl

 1850

 H 4- (1-methylpyrrol-3-yl) -phenyl

 1851

 H 4- (furan-2-yl) -phenyl

 1852

 H 4- (furan-3-yl) -phenyl

 1853

 H 4- (thiophen-2-yl) -phenyl

 1854

 H 4- (thiophen-3-yl) -phenyl

 1855

 H 4- (5-propylthien-2-yl) -phenyl

 1856

 H 4- (pyrazol-1-yl) -phenyl

 1857

 H 4- (pyrazol-3-yl) -phenyl

 1858

 H 4- (pyrazol-4-yl) -phenyl

 1859

 H 4- (1-methyl-1H-pyrazol-4-yl) -phenyl

 1860

 H 4- (1-ethyl-1H-pyrazol-4-yl) -phenyl

 1861

 H 4- (1-methyl-1H-pyrazol-5-yl) -phenyl

 1862

 H 4- (1H-imidazol-2-yl) -phenyl

 1863

 H 4- (imidazol-1-yl) -phenyl

 1864

 H 4- (1-methylimidazol-2-yl) -phenyl

 Do not.

 R1 Ar

 1865

 H 4- (oxazol-2-yl) -phenyl

 1866

 H 4- (oxazol-4-yl) -phenyl

 1867

 H 4- (oxazol-5-yl) -phenyl

 1868

 H 4- (isoxazol-3-yl) -phenyl

 1869

 H 4- (isoxazol-4-yl) -phenyl

 1870

 H 4- (isoxazol-5-yl) -phenyl

 1871

 H 4 - ([1,2,3] -triazol-1-yl) -phenyl

 1872

 H 4 - ([1,2,4] -triazol-1-yl) -phenyl

 1873

 H 4 - ([1,2,3] -triazol-2-yl) -phenyl

 1874

 H 4- (4H- [1,2,4] -triazol-3-yl) -phenyl

 1875

 H 4 - ([1,2,4] -triazol-4-yt) -phenyl

 1876

 H 4- (2H- [1,2,3] -triazol-4-yl) -phenyl

 1877

 H 4- (4-methyl-4H- [1,2,4] -triazol-3-yl) -phenyl

 1878

 H 4- (2-methyl-2H- [1,2,3] -triazol-4-yl) -phenyl

 1879

 H 4 - ([1,3,4] -oxadiazol-2-yl) -phenyl

 1880

 H 4 - ([1,2,4] -oxadiazol-3-yl) -phenyl

 1881

 H 4 - ([1,2,4] -oxadiazol-5-yl) -phenyl

 1882

 H 4 - ([1,2,3] -oxadiazol-4-yl) -phenyl

 1883

 H 4 - ([1,2,3] -oxadiazol-5-yl) -phenyl

 1884

 H 4 - ([1,2,3] -thiadiazol-4-yl) -phenyl

 1885

 H 4- (1H-tetrazol-5-yl) -phenyl

 1886

 H 4- (tetrazol-1-yl) -phenyl

 1887

 H 4- (2-methyl-2H-tetrazol-5-yl) -phenyl

 1888

 H 4- (1-methyl-1H-tetrazol-5-yl) -phenyl

 1889

 H 4-furazan-3-yl-phenyl

 1890

 H 4- (pyrid-2-yl) -phenyl

 1891

 H 4- (pyrid-3-yl) -phenyl

 1892

 H 4- (pyrid-4-yl) -phenyl

 1893

 H 4- (pyrimidin-2-yl) -phenyl

 Do not.

 R1 Ar

 1894

 H 4- (pyrimidin-4-yl) -phenyl

 1895

 H 4- (pyrimidin-5-yl) -phenyl

 1896

 H 5-isopropylthiophene-2-yl

 1897

 H 2-chlorothiophene-5-yl

 1898

 H 2,5-dichlorothiophene-4-yl

 1899

 H 2,3-dichlorothiophene-5-yl

 1900.

 H 2-Chloro-3-nitrothiophene-5-yl

 1901

 H 2- (phenylsulfonyl) -thiophene-5-yl

 1902

 H 2- (pyridin-2-yl) thiophene-5-yl

 1903

 H 2- (5- (trifluoromethyl) isoxazol-3-yl) -thiophene-5-yl

 1904

 H 2- (2-methylthiazol-4-yl) -thiophene-5-yl

 1905

 H 1-methyl-1H-imidazol-4-yl

 1906

 H 1,2-dimethyl-1H-imidazol-4-yl

 1907

 H 3,5-dimethylisoxazol-4-yl

 1908

 H thiazol-2-yl

 1909

 H 4-methylthiazol-2-yl

 1910

 H 4-isopropylthiazol-2-yl

 1911

 H 4-trifluoromethylthiazol-2-yl

 1912

 H 5-methylthiazol-2-yl

 1913

 H 5-isopropylthiazol-2-yl

 1914

 H 5-trifluoromethylthiazol-2-yl

 1915

 H 2,4-dimethylthiazol-5-yl

 1916

 H 2-acetamido-4-methylthiazol-5-yl

 1917

 H 4H- [1,2,4] triazol-3-yl

 1918

 H 5-methyl-4H- [1,2,4] triazol-3-yl

 1919

 H 4-methyl-4H- [1,2,4] triazol-3-yl

 1920

 H 5-isopropyl-4H- [1,2,4] triazol-3-yl

 1921

 H 5-trifluoromethyl-4H- [1,2,4] triazol-3-yl

 1922

 H 4,5-dimethyl-4H- [1,2,4] triazol-3-yl

 Do not.

 R1 Ar

 1923

 H 5-isopropyl-4-methyl-4H- [1,2,4] triazol-3-yl

 1924

 H 5-trifluoromethyl-4-methyl-4H- [1,2,4] triazol-3-yl

 1925

 H [1,3,4] thiadiazol-2-yl

 1926

 H 5-methyl- [1,3,4] thiadiazol-2-yl

 1927

 H 5-isopropyl- [1,3,4] thiadiazol-2-yl

 1928

 H 5-trifluoromethyl- [1,3,4] thiadiazol-2-yl

 1929

 H 3-bromo-2-chloropyrid-5-yl

 1930

 H 2- (4-morpholino) -pyrid-5-yl

 1931

 H 2-phenoxypyrid-5-yl

 1932

 H (2-isopropyl) -pyrimidin-5-yl

 1933

 H (5-isopropyl) -pyrimidin-2-yl

 1934

 H 8-quinolyl

 1935

 H 5-isoquinolyl

 1936

 H 2- (trifluoroacetyl) -1,2,3,4-tetrahydroisoquinolin-7-yl

 1937

 H 5-Chloro-3-methylbenzothiophene-2-yl

 1938

 H 3,4-dihydro-4-methyl-2H-benzo [b] [1,4] oxazinyl

 1939

 H benzothiazol-6-yl

 1940

 H benzo [2,1,3] oxadiazol-4-yl

 1941

 H 5-chlorobenzo [2,1,3] oxadiazol-4-yl

 1942

 H 7-chlorobenzo [2,1,3] oxadiazol-4-yl

 1943

 H benzo [2,1,3] thiadiazol-4-yl

 1944

 H 6-chloroimidazo [2,1-b] thiazolyl

Table B-1: Compounds of the formula Iu, where Ar has the meaning given in one of the rows of table B.

Table B-2: Compounds of formula Iv, where Ar has the meaning given in one of the rows of table B.

Table B-3: Compounds of the formula Iw, where Ar has the meaning given in one of the rows of B.

Table B-4: Compounds of the formula Ix, where Ar has the meaning given in one of the rows of table B. 5

Table B-5: Compounds of the formula Iy, where Ar has the meaning given in one of the rows of table B.

Table B-6: Compounds of the formula Iz, where Ar has the meaning given in one of the rows of table B.

Table B

 Do not.

 Ar

 1945

 4- (trifluoromethoxy) -phenyl

 1946

 3- (trifluoromethoxy) -phenyl

 1947

 4-cyanophenyl

 1948

 4-methylphenyl

 1949

 4-ethylphenyl

 1950

 4-propylphenyl

 1951

 4-methoxyphenyl

 1952

 4-fluorophenyl

 1953

 4-chlorophenyl

 1954

 4-bromophenyl

 1955

 3- (trifluoromethyl) phenyl

 1956

 4- (trifluoromethyl) phenyl

 1957

 2- (trifluoromethyl) phenyl

 1958

 3,4-difluorophenyl

 1959

 4-bromo-3-fluorophenyl

 1960

 4-bromo-2-fluorophenyl

 1961

 4-bromo-2,5-difluorophenyl

 1962

 2-fluoro-4-isopropylphenyl

 1963

 4-hydroxyphenyl

 1964

 4-isopropylphenyl

 1965

 4-sec-butylphenyl

 1966

 4-isobutylphenyl

 1967

 4- (1,1-dimethylpropyl) -phenyl

 1968.

 4-vinylphenyl

 1969

 4-isopropenylphenyl

 1970

 4- (fluoromethyl) phenyl

 1971.

 3- (fluoromethyl) phenyl

 Do not.

 Ar

 1972

 2- (fluoromethyl) phenyl

 1973

 4- (difluoromethyl) phenyl

 1974

 3- (difluoromethyl) phenyl

 1975

 2- (difluoromethyl) phenyl

 1976

 4- (1-fluoroethyl) -phenyl

 1977.

 4 - ((S) -1-fluoroethyl) -phenyl

 1978.

 4 - ((R) -1-fluoroethyl) -phenyl

 1979.

 4- (2-fluoroethyl) -phenyl

 1980.

 4- (1,1-difluoroethyl) -phenyl

 1981.

 4- (2,2-difluoroethyl) -phenyl

 1982

 4- (2,2,2-trifluoroethyl) -phenyl

 1983

 4- (3-fluoropropyl) -phenyl

 1984.

 4- (2-fluoropropyl) -phenyl

 1985

 4 - ((S) -2-fluoropropyl) -phenyl

 1986

 4 - ((R) -2-fluoropropyl) -phenyl

 1987.

 4- (3,3-difluoropropyl) -phenyl

 1988

 4- (3,3,3-trifluoropropyl) -phenyl

 1989

 4- (1-Fluoro-1-methylethyl) -phenyl

 1990.

 4- (2-Fluoro-1-methylethyl) -phenyl

 1991

 4 - ((S) -2-fluoro-1-methylethyl) -phenyl

 1992.

 4 - ((R) -2-fluoro-1-methylethyl) -phenyl

 1993

 4- (2,2-Difluoro-1-methylethyl) -phenyl

 1994

 4 - ((S) -2,2-difluoro-1-methylethyl) -phenyl

 nineteen ninety five.

 4 - ((R) -2,2-difluoro-1-methylethyl) -phenyl

 nineteen ninety six.

 4- (2,2,2-trifluoro-1-methylethyl) -phenyl

 1997

 4 - ((S) -2,2,2-trifluoro-1-methylethyl) -phenyl

 1998

 4 - ((R) -2,2,2-trifluoro-1-methylethyl) -phenyl

 1999.

 4- (2-Fluoro-1-fluoromethylethyl) -phenyl

 2000

 4- (1-difluoromethyl-2,2-difluoroethyl) -phenyl

 Do not.

 Ar

 2001

 4- (1,1-dimethyl-2-fluoroethyl) -phenyl

 2002

 4-ethoxyphenyl

 2003

 4-propoxyphenyl

 2004

 4-isopropoxyphenyl

 2005

 4-butoxyphenyl

 2006

 4- (fluoromethoxy) -phenyl

 2007

 4- (difluoromethoxy) -phenyl

 2008

 4- (2-fluoroethoxy) -phenyl

 2009

 4- (2,2-difluoroethoxy) -phenyl

 2010

 4- (2,2,2-trifluoroethoxy) -phenyl

 2011

 4- (1,1,2,2-tetrafluoroethoxy) -phenyl.

 2012

 4-cyclopropylphenyl

 2013

 4-cyclobutylphenyl

 2014.

 4-cyclopentylphenyl

 2015

 4- (2,2-difluorocyclopropyl) -phenyl

 2016.

 3-fluoro-4-isopropylphenyl

 2017

 4- (1-hydroxy-1-methylethyl) -thienyl

 2018.

 4- (2-hydroxy-2-methylpropyl) -phenyl

 2019.

 4-acetylphenyl

 2020

 4-carboxyphenyl

 2021

 4- (O-benzyl) -phenyl

 2022

 4- (2-methoxyethoxy) -phenyl

 2023

 4- (CH2-N (CH3) 2) -phenyl

 2024

 4- (NH-CO-NH2) -phenyl

 2025

 4- (methylsulfanyl) -phenyl

 2026

 4- (fluoromethylsulfanyl) -phenyl

 2027

 4- (difluoromethylsulfanyl) -phenyl

 2028

 4- (trifluoromethylsulfanyl) -phenyl

 2029

 4- (methylsulfonyl) -phenyl

 Do not.

 Ar

 2030

 4- (N-Methoxy-N-methyl-amino) -phenyl

 2031

 4- (methoxyamino) -phenyl

 2032

 4- (ethoxyamine) -phenyl

 2033

 4- (N-methylaminooxy) -phenyl

 2034

 4- (N, N-dimethylaminooxy) -phenyl

 2035

 4- (azetidin-1-yl) -phenyl

 2036

 4- (2-Methylazetidin-1-yl) -phenyl

 2037

 4 - ((S) -2-methylazetidin-1-yl) -phenyl

 2038

 4 - ((R) -2-Methylazetidin-1-yi) -phenyl

 2039

 4- (3-fluoroazetidin-1-yl) -phenyl

 2040

 4- (3-Methoxyazetidin-1-yl) -phenyl

 2041

 4- (3-hydroxyazetidin-1-yl) -phenyl

 2042

 4- (pyrrolidin-1-yl) -phenyl

 2043

 4- (pyrrolidin-2-yl) -phenyl

 2044

 4 - ((S) -pyrrolidin-2-yl) -phenyl

 2045

 4 - ((R) -pyn-olidin-2-yl) -phenyl

 2046

 4- (pyrrolidin-3-yl) -phenyl

 2047

 4 - ((S) -pyrrolidin-3-yl) -phenyl

 2048

 4 - ((R) -pyrrolidin-3-yl) -phenyl

 2049

 4- (2-fluoropyrrolidin-1-yl) -phenyl

 2050

 4 - ((S) -2-fluoropyrrolidin-1-yl) -phenyl

 2051

 4 - ((R) -2-fluoropyrrolidin-1-yl) -phenyl

 2052

 4- (3-fluoropyrrolidin-1-yl) -phenyl

 2053

 4 - ((S) -3-fluoropyrrolidin-1-yl) -phenyl

 2054

 4 - ((R) -3-fluoropyrrolidin-1-yl) -phenyl

 2055

 4- (2,2-difluoropyrrolidin-1-yl) -phenyl

 2056

 4- (3,3-Difluorooyrrolidin-1-yl) -phenyl

 2057

 4- (2-methylpyrrolidin-1-yl) -phenyl

 2058

 4 - ((S) -2-methylpyrrolidin-1-yl) -phenyl

 Do not.

 Ar

 2059

 4 - ((R) -2-methylpyrrolidin-1-yl) -phenyl

 2060

 4- (3-methylpyrrolidin-1-yl) -phenyl

 2061

 4 - ((S) -3-methylpyrrolidin-1-yl) -phenyl

 2062

 4 - ((R) -3-methylpyrrolidin-1-yl) -phenyl

 2063

 4- (1-methylpyrrolidin-2-yl) -phenyl

 2064

 4 - ((S) -1-methylpyrrolidin-2-yl) -phenyl

 2065

 4 - ((R) -1-methylpyrrolidin-2-yl) -phenyl

 2066

 4- (1-methylpyrrolidin-3-yl) -phenyl

 2067

 4 - ((S) -1-methylpyrrolidin-3-yl) -phenyl

 2068

 4 - ((R) -1-methylpyrrolidin-3-yl) -phenyl

 2069

 4- (2,2-dimethylpyrrolidin-1-yl) -phenyl

 2070

 4- (3,3-dimethylpyrrolidin-1-yl) -phenyl

 2071

 4- (2-Trifluoromethylpyrrolidin-1-yl) -phenyl

 2072

 4 - ((S) -2-trifluoromethylpyrrolidin-1-yl) -phenyl

 2073

 4 - ((R) -2-trifluoromethylpyrrolidin-1-yl) -phenyl

 2074

 4- (3-Trifluoromethylpyrrolidin-1-yl) -phenyl

 2075

 4 - ((S) -3-Trifluoromethylpyrrolidin-1-yl) -phenyl

 2076

 4 - ((R) -3-trifluoromethylpyrrolidin-1-yl) -phenyl

 2077

 4- (2-oxopyrrolidin-1-yl) -phenyl

 2078

 4- (2-oxo-oxazolidin-3-yl) -phenyl

 2079

 4- (piperidin-1-yl) -phenyl

 2080

 4- (2-methylpiperidin-1-yl) -phenyl

 2081

 4 - ((S) -2-methylpiperidin-1-yl) -phenyl

 2082

 4 - ((R) -2-methylpiperidin-1-yl) -phenyl

 2083

 4- (piperazin-1-yl) -phenyl

 2084

 4- (4-methylpiperazin-1-yl) -phenyl

 2085

 4- (morpholin-4-yl) -phenyl

 2086

 4- (thiomorpholin-4-yl) -phenyl

 2087

 4- (1-oxo-thiomorpholin-4-yl) -phenyl

 Do not.

 Ar

 2088

 4- (1,1-dioxo-thiomorpholin-4-yl) -phenyl

 2089

 4- (pyrrol-1-yl) -phenyl

 2090

 4- (pyrrol-2-yl) -phenyl

 2091

 4- (pyrrole-3-yl) -phenyl

 2092

 4- (1-methylpyrrol-2-yl) -phenyl

 2093

 4- (1-methylpyrrol-3-yl) -phenyl

 2094

 4- (furan-2-yl) -phenyl

 2095

 4- (furan-3-yl) -phenyl

 2096

 4- (thiophen-2-yl) -phenyl

 2097

 4- (thiophen-3-yl) -phenyl

 2098

 4- (5-propylthien-2-yl) -phenyl

 2099

 4- (pyrazol-1-yl) -phenyl

 2100

 4- (pyrazol-3-yl) -phenyl

 2101.

 4- (pyrazol-4-yl) -phenyl

 2102

 4- (1-methyl-1H-pyrazol-4-yl) -phenyl

 2103

 4- (1-ethyl-1H-pyrazol-4-yl) -phenyl

 2104

 4- (1-methyl-1H-pyrazol-5-yl) -phenyl

 2105

 4- (1H-imidazol-2-yl) -phenyl

 2106

 4- (imidazol-1-yl) -phenyl

 2107

 4- (1-methylimidazol-2-yl) -phenyl

 2108

 4- (oxazol-2-yl) -phenyl

 2109

 4- (oxazol-4-yl) -phenyl

 2110

 4- (oxazol-5-yl) -phenyl

 2111

 4- (isoxazol-3-yl) -phenyl

 2112

 4- (isoxazol-4-yl) -phenyl

 2113

 4- (isoxazol-5-yl) -phenyl

 2114

 4 - ([1,2,3] -triazot-1-yl) -phenyl

 2115

 4 - ([1,2,4] -triazol-1-yl) -phenyl

 2116

 4 - ([1,2,3] -triazol-2-yl) -phenyl

 Do not.

 Ar

 2117

 4- (4H- [1,2,4] -triazol-3-yl) -phenyl

 2118

 4 - ([1,2,4] -triazol-4-yl) -phenyl

 2119.

 4- (2H- [1,2,3] -triazol-4-yl) -phenyl

 2120

 4- (4-methyl-4H- [1,2,4] -triazol-3-yl) -phenyl

 2121

 4- (2-methyl-2H- [1,2,3] -triazol-4-yl) -phenyl

 2122

 4 - ([1,3,4] -oxadiazol-2-yl) -phenyl

 2123

 4 - ([1,2,4] -oxadiazol-3-yl) -phenyl

 2124

 4 - ([1,2,4] -Oxadiazol-5-yl) -phenyl

 2125

 4 - ([1,2,3] -Oxadiazol-4-yl) -phenyl

 2126

 4 - ([1,2,3] -oxadiazol-5-yl) -phenyl

 2127

 4 - ([1,2,3] -thiadiazol-4-yl) -phenyl

 2128

 4- (1H-tetrazol-5-yl) -phenyl

 2129

 4- (tetrazol-1-yl) -phenyl

 2130

 4- (2-methyl-2H-tetrazol-5-yl) -phenyl

 2131

 4- (1-methyl-1H-tetrazol-5-yl) -phenyl

 2132

 4-furazan-3-il-phenyl

 2133

 4- (pyrid-2-yl) -phenyl

 2134.

 4- (pyrid-3-yl) -phenyl

 2135

 4- (pyrid-4-yl) -phenyl

 2136

 4- (pyrimidin-2-yl) -phenyl

 2137

 4- (pyrimidin-4-yl) -phenyl

 2138

 4- (pyrimidin-5-yl) -phenyl

 2139

 5-isopropylthiophene-2-yl

 2140

 2-chlorothiophene-5-yl

 2141

 2,5-dichlorothiophene-4-yl

 2142

 2,3-dichlorothiophene-5-yl

 2143

 2-chloro-3-nitrothiophene-5-yl

 2144

 2- (phenylsulfonyl) -thiophene-5-yl

 2145

 2- (pyridin-2-yl) thiophene-5-yl

 Do not.

 Ar

 2146

 2- (5- (trifluoromethyl) isoxazol-3-yl) -thiophene-5-yl

 2147

 2- (2-methylthiazol-4-yl) -thiophene-5-yl

 2148

 1-methyl-1H-imidazol-4-yl

 2149.

 1,2-dimethyl-1H-imidazol-4-yl

 2150

 3,5-dimethylisoxazol-4-yl

 2151

 thiazol-2-yl

 2152

 4-methylthiazol-2-yl

 2153

 4-isopropylthiazol-2-yl

 2154

 4-trifluoromethylthiazol-2-yl

 2155

 5-methylthiazol-2-yl

 2156

 5-isopropylthiazol-2-yl

 2157

 5-trifluoromethylthiazol-2-yl

 2158

 2,4-dimethylthiazol-5-yl

 2159

 2-acetamido-4-methylthiazol-5-yl

 2160

 4H- [1,2,4] triazol-3-yl

 2161

 5-methyl-4H- [1,2,4] triazol-3-yl

 2162.

 4-methyl-4H- [1,2,4] triazol-3-yl

 2163

 5-Isopropyl-4H- [1,2,4] triazot-3-yl

 2164

 5-trifluoromethyl-4H- [1,2,4] triazol-3-yl

 2165

 4,5-dimethyl-4H- [1,2,4] triazol-3-yl

 2166.

 5-Isopropyl-4-methyl-4H- [1,2,4] triazol-3-yl

 2167.

 5-trifluoromethyl-4-methyl-4H- [1,2,4] triazol-3-yl

 2168.

 [1,3,4] thiadiazol-2-yl

 2169

 5-methyl- [1,3,4] thiadiazol-2-yl

 2170

 5-isopropyl- [1,3,4] thiadiazol-2-yl

 2171

 5-trifluoromethyl- [1,3,4] thiadiazol-2-yl

 2172

 3-bromo-2-chloropyrid-5-yl

 2173

 2- (4-morpholino) -pyrid-5-yl

 2174

 2-phenoxypyrid-5-yl

 Do not.

 Ar

 2175

 (2-Isopropyl) -pyrimidin-5-yl

 2176

 (5-Isopropyl) -pyrimidin-2-yl

 2177

 8-quinolyl

 2178.

 5-isoquinolyl

 2179

 2- (trifluoroacetyl) -1,2,3,4-tetrahydroisoquinolin-7-yl

 2180

 5-Chloro-3-methylbenzothiophene-2-yl

 2181.

 3,4-dihydro-4-methyl-2H-benzo [b] [1,4] oxazinyl

 2182.

 benzothiazol-6-yl

 2183

 benzo [2,1,3] oxadiazol-4-yl

 2184.

 5-Chlorobenzo [2,1,3] oxadiazol-4-yl

 2185

 7-chlorobenzo [2,1,3] oxadiazol-4-yl

 2186

 benzo [2,1,3] thiadiazol-4-yl

 2187

 6-chloroimidazo [2,1-b] thiazolyl

The compounds of the formula I where R3 and R1a are both hydrogen and can be prepared by analogy with the methods that are well known in the art. A preferred method for the preparation of compounds I is outlined in scheme 1:

Scheme 1 5

In scheme 1 R1, R2, R2a, R8, R8a, R9, X and Ar have the meanings given above. PG is an amino protecting group such as tert-butoxycarbonyl or benzyl. Suitable protecting groups are disclosed, for example, in P. Kocienski, Protecting Groups, Tieme-Verland, Stuttgart 2000, Chapter 6. Hal is halogen, in particular bromine or chlorine. 10

According to scheme 1, following standard methods for nucleophilic aromatic substitution reactions, compound II is reacted in step a) with an amino alcohol VIII in the presence of a base, such as hydride of

sodium, sodium alkoxide or potassium carbonate in an organic solvent such as dimethylformamide, dioxane or tetrahydrofuran (see for example WO 2004/000830).

Alternatively, compounds III may be prepared from compounds II and VIII through reactions catalyzed with palladium described in the literature, for example, in J. Am. Chem. Soc. 2001, 123, pp. 10770-10771. An example of a suitable catalyst for Pd (0) is Pd (OAc) 2 which is normally used in the presence of a ligand such as [1,1 '] binaphthalenyl-2-yl-di-tert- butyl phosphate in solvents such as toluene or 1,2-dimethoxy ethane.

The nitro compound III thus obtained is reduced in step b) by conventional means to give the corresponding amino compound IV. The reaction conditions required correspond to the usual conditions for the reduction of aromatic nitro groups, which have been extensively described in the literature (see, for example, J. 10 March, Advanced Organic Chemistry, 3rd ed., J. Wiley & Sons , New-York, 1985, p. 1138 and the literature cited in this reference). The reduction is achieved, for example, by reacting the nitro III compound with a metal such as iron, zinc or tin under acidic reaction conditions, that is, using nascent hydrogen, or using a hydride complex such as lithium aluminum hydride. or sodium borohydride, preferably in the presence of nickel or cobalt transition metal compounds such as NiCl2 (P (phenyl3) 2 'or CoCl2' (see Ono et al. Chem, 15 Ind. (London), 1983 p. 480 ), or using NaBH2S3 (see Lalancette et al., Can. J. Chem. 49, 1971, p. 2990), it being possible to carry out these reductions, depending on the reagent given, in substance or in a solvent or diluent. , the reduction from III to IV can be carried out with hydrogen in the presence of a transition metal catalyst, for example, using hydrogen in the presence of catalysts based on platinum, palladium, nickel, ruthenium or rhodium. the goal Transition in elemental form or in the form of a complex compound, of a salt or of an oxide of the transition metal, being possible, for the purpose of the activity modification, to use usual co-ligands, for example, organic compounds phosphine, such as triphenylphosphine, tricyclohexylphosphine or tri-n-butylphosphines or phosphites. The catalyst is usually used in amounts ranging from 0.001 to one mole per mole of compound III, calculated as catalyst metal. In a preferred variant, the reduction is effected using tin (II) chloride in analogy with the methods described in Bioorganic and Medicinal 25 Chemistry Letters 2002, 12 (15), pp. 1917-1919 and J. Med. Chem. 2002, 45 (21), pp. 4679-4688. The reaction of III with tin (II) chloride is preferably carried out in an inert organic solvent, preferably an alcohol such as methanol, ethanol, isopropanol or butanol.

The compound IV thus obtained is reacted with an arylsulfonylchloride Cl-SO2-Ar, preferably in the presence of a base, according to standard procedures of the art to provide compound V. The reaction 30 represented in the scheme 1 step c) takes site under the reaction conditions that are customary for the preparation of arylsulfonamide compounds or arylsulfonic esters, respectively, and which are described, for example, in J. March, Advanced Organic Chemistry, 3rd edition, Jonh Wiley & Sons, New York 1985 p 444 and in the literature cited there, European J. Org. Chem. 2002 (13), pp. 2094-2108, Tetrahedron 2001, 57 (27) pp. 5885-5895, Bioorganic and Medicinal Chemistry Letters, 2000, 10 (8), pp. 835-838 and Synthesis 2000 (1), pp. 103-108. The reaction usually takes place in an inert solvent, for example in an ether, such as diethyl ether, diisopropyl ether, methyltertbutyl ether or tetrahydrofuran, a halohydrocarbon, such as dichloromethane, an aliphatic or cycloaliphatic hydrocarbon, such as pentane, hexane or cyclohexane, or an aromatic hydrocarbon, such as toluene, xylene, cumene and the like, or in a mixture of the solvents mentioned above. The reaction of IV with Cl-SO2-Ar is usually carried out in the presence of an auxiliary base. Suitable bases are inorganic bases, such as sodium carbonate or potassium carbonate, or sodium hydrogen carbonate or potassium hydrogen carbonate, and organic bases, for example trialkylamines such as triethylamine, or pyridine compounds, such as pyridine, lutidine and the like. The latter compounds can at the same time serve as solvents. The auxiliary base is usually used in at least equimolar amounts, based on the amine compound IV.

In step d) the protective group PG is cleaved by conventional means (see for example P. Kocienski, Protecting 45 Groups, Tieme-Verlang, Stuttgar 2000, Chapter 6), thereby producing a compound I where R1a is hydrogen.

Scheme 2

Scheme 2 shows the synthesis of the compounds of the formula I where R1, R1a, R2, R2a, R8, R8a, R9, X and Ar have the meanings given above. Hal is halogen, in particular bromine and chlorine. The reaction steps a), b), and c) to obtain compounds I in scheme 2 follow the reaction steps a), b), and c) described for scheme 1.

Compounds II can be obtained from commercial sources. 5

Scheme 3

If R9 is alkoxy, compounds II can also be synthesized according to scheme 3. Following standard methods, commercially available compounds XI, where Hal is halogen, in particular bromine or chlorine, is reacted with an alkaline salt of an alcohol, for example, sodium or potassium salt of for example methanol, ethanol or n-10 propanol, in the corresponding alcohol as a solvent, for example, methanol, ethanol or n-propanol. The mixture thus obtained of compounds II and XII can be separated, for example, by recrystallization from a solvent or by chromatography to provide the desired compound II. Protected amino alcohols VIII are also commercially available or can be obtained from commercially available amino alcohols by selective protection of the amino groups of these compounds according to standard methods (see, for example P. Kocienski, 15 Protecting Groups, loc. Cit.) .

Amino alcohols IX may also be commercially available or may be prepared by analogy with methods that are well known in the art.

An experienced person will also appreciate that the compounds of the formula I where R 3 is different from hydrogen, can be obtained by selective alkylation of the sulfonamide group in the compounds of the formula V or I.

If R1 or R1a in compound I is (are) allyl, the allyl group or groups can be cleaved to obtain a compound I 'or I ", where R is hydrogen. The cleavage of the allyl group is achieved, for example, by reacting I [R1 = allyl] with an allyl trapping agent, such as mercaptobenzoic acid or 1,3-dimethylbarbituric acid, in the presence of catalytic amounts of palladium compounds (0) or palladium compounds that are capable of forming a palladium compound ( 0) under reaction conditions, for example, palladium dichloride, tetrakis (triphenylphosphine) palladium (0) or tris 25 (dibenzylidenacetone) dipaladium (0), advantageously in combination with phosphine ligands, such as for example triarylphosphines, such as triphenylphosphine, trialkylphosphines, such as tributylphosphine, and cycloalkylphosphines, such as tricyclohexylphosphine, and especially with phosphine chelate ligands such as 2,2'-bis (diphenylphosphine) -1,1'-binaphthyl or 1,4-bis (diphenylphosphine) buta no, using methods known in the literature (with respect to the removal of N-allyl in the presence of mercaptobenzoic acid, see WO 94/24088; with respect to the elimination in the presence of 1,3-30 dimethylbarbituric acid, see J. Am Chem Soc 2001, 123 (28), pp 6,801-6808 and J. Org. Chem. 2002, 67 (11) pp 3718-3723). Alternatively, N-allyl cleavage can also be carried out by reacting it in the presence of rhodium compounds, such as tris (triphenylphosphine) chlororodium (I), using methods known in the literature (see J. Chem. Soc., Perkin Transaction I: Organic and Bio-Organic Chemistry 1999 (21) pp. 3089-3104 and Tetrahedron Asymmetry 1997, 8 (20), pp. 3387-3391). If R1 or R1a in a compound I is (are) allyl, the allyl group can also be converted into an n-35 propyl group by hydrogenation in the presence of Pd-C as a catalyst.

If nothing else is indicated, the reactions described above are generally carried out in a solvent at temperatures between room temperature and the boiling temperature of the solvent used. Alternatively, the activation energy required for the reaction can be introduced into the reaction mixture using microwaves, something that has proven to be valuable, in particular, in the case of reactions catalyzed by transition metals (with respect to the reactions using microwave, see Tetrahedron 2001, 57, p. 9199 ff. p. 9225 ff. and also, in general, "Microwaves in Organic Synthesis", André Loupy (Ed.), Wiley-VCH 2002.

Cl-SO2-Ar sulfonylchlorides are also commercially available or can be prepared according to standard synthetic methods. Sulfonylchlorides containing a fluorinated Ra radical can be prepared by different synthetic routes, for example, by reacting a suitable hydroxy or oxo precursor (for example, a compound 45 Cl-SO2-Ar, which carries a substituted hydroxy or oxo radical) with agents fluoridants such as DAST (diethylaminosulfurotrifluoride), morpholine-DAST, deoxofluor (bis (-2-methoxyethyl) aminosulfur trifluoride), reagent of Ishikawa (N, N-diethyl- (1,1,2,3,3,3-hexafluoropropyl) amine; Journal of Fluor Chemistry, 1989, 43, 371-377). More conventionally, the hydroxy group of an aromatic compound that carries a substituted hydroxy radical but not a chlorosulfonyl group, is transformed into a leaving group which is replaced by a fluoride ion (J. Org. Chem., 1994, 59, 50

2898-22901; Tetrahedron Letters, 1998, 7305-6; J. Org. Chem., 1998, 63, 9587-9589, Synthesis, 1987, 920-21)). 9587-9589, Synthesis, 1987, 920-21)). Subsequent direct chlorosulfonation with chlorosulfonic acid (Heterocicles, 2001, 55, 9,1789-1803; J. Org. Chem., 2000, 65, 1399-1406) or a two-stage process that first prepares the sulfonic acid derivatives that they are then transformed into the sulfonylchlorides with, for example, chlorosulfonic acid, phosphorus pentachloride (Eur. J. Med. Quim., 2002, 36, 809-828) and the like, produces the desired sulfonylchloride 5 (Tetrahedron Letters, 1991, 33 , 50 from 7787-7788). Sulfonylchlorides can also be prepared by diazotization of a suitable Ar-NH2 amine precursor with sodium nitrite under acidic conditions and reaction with sulfur dioxide in acetic acid (scheme (iii); J. Org Chem, 1960, 25, 1824-26) ; by oxidation of suitable heteroaryl thiols HS-Ar or heteroaryl-benzyl-thioethers C6H5-CH2-S-Ar with chlorine (Synthesis, 1998, 36-38; J. Am. Chem. Soc., 1950, 74, 4890-92) ; directly to the corresponding sulfonyl chlorides. The following are known in the art or can be prepared by standard methods, for example mercapto-pyrimidine or pyrimidinyl-benzylthioether precursors can, for example, be prepared according to the literature (Chemische Berichte, 1960, 1208-11; Chemische Berichte , 1960, 95, 230-235; Collection Czechoslow. Chem. Comm., 1959, 24, 1667-1671; Austr. J. Chem., 1966, 19, 2321-30; Chemiker-Zeitung, 101, 6, 1977, 305-7; Tetrahedron, 2002, 58, 887-890; Synthesis, 1983, 641-645.

An experienced person will readily appreciate that the compounds of the formula I can also be obtained from structurally similar compounds by interconversion of functional groups. In particular, the N Ra radicals linked to N can be introduced into the compounds of the formula I by reacting the corresponding halogenated compound, this is a compound of the formula I, which instead of Ra carries a halogen atom, in particular an atom of bromine or iodine, with a primary or secondary amine in the presence of a base, preferably also in the presence of a palladium catalyst in terms of the Buchwald-Hartwig reaction. twenty

In the following schemes 4 to 6 several routes are shown that are suitable for preparing benzenesulfonyl chlorides bearing a fluorinated propyl radical.

Scheme 4:

The intermediate 4- (1,1-difluoropropan-2-yl) benzene-1-sulfonyl chloride can be prepared from commercially available 2-25 phenylpropanoic acid. In the first stage a) 2-phenylpropanoic acid is converted into the alkyl ester by esterification with an alcohol (for example, methanol or ethanol), under acid catalysis (for example, HCl, SO2Cl2). The ester can be reduced to the corresponding 2-phenyl propanol and by a reducing agent such as DIBAL (diisobutylaluminum hydride). The aldehyde is converted into the 1,1-difluoro-2-propyl derivative by reaction with a suitable fluorine reagent such as DAST (diethylaminosulfurtrifluoride), morpholine-DAST, deoxofluor (bis (2-methoxyethyl) 30 aminosulfur trifluoride), Ishikawa reagent ( N, N-diethyl- (1,1,2,3,3,3-hexafluoropropyl) amine; Journal of Fluor Chemistry, 1989, 43, 371-377) (step b). The 1,1-difluoro-2-phenylpropane thus obtained can be converted to 4- (1,1-difluoro-2-propyl) benzenesulfonyl chloride either by direct chlorosulfonation with chlorosulfonic acid (Heterocicles, 2001, 55, 9, 1789-1803; J. Org. Chem., 2000, 65, 1399-1406) (stage c) or by a two-stage process that first prepares the sulphonic acid derivatives (stage d) which are then transformed into the sulfonylchlorides (stage e) by reaction with, for example, chlorosulfonic acid, phosphorus pentachloride ((Eur. J. Med. Chem., 2002, 36, 809-828); through diazotization of suitable amine precursors with sodium nitrite under acidic conditions and reaction with sulfur dioxide in acetic acid (J. Org. Chem., 1960, 25, 1824-26); oxidation of suitable heteroarylthiols or heteroaryl-benzylthioethers with chlorine (Synthesis, 1998, 36-38; J. Am. Chem Soc., 1950, 74, 4890-92) direct to the corresponding sulfonyl chlorides.

The synthesis shown in scheme 4 can also be carried out using (R) -2-phenylpropanoic acid and (S) -2-phenylpropanoic acid, respectively, to give the corresponding 4- (1,1-difluoropropan-2- chlorides il) chiral benzene-1sulfonyl.

Scheme 5:

The 4- (1,1,1-Trifluoropropan-2-yl) benzene-1-sulfonyl chloride intermediate can be prepared from the commercially available 2,2,2-trifluoro-1-phenyletanone by a synthetic route shown in Scheme 5. The ketone can be converted into 3,3,3-trifluoro-2-phenylpropene by a Wittig reaction with a suitable ilide, such as methylene-triphenylphosphane (prepared by reaction of methyltriphenylphosphonium halide and a suitable base such as 5 lithium diisopropylamide or potassium tertbutoxide) or according to the Horner-Emmons reaction by reacting the ketone with a suitable phosphonate such as a diethylmethylphosphonate and a suitable base such as lithium diisopropylamide or potassium tertbutoxide. The 3,3,3-trifluoro-2-phenylpropene thus obtained can then be reduced to saturated alkane by catalytic hydrogenation (for example Pd-C) followed by conversion to sulfonyl chloride by the methods described in Scheme 4. 10

The synthesis of scheme 5 can be carried out using a chiral catalyst for the hydrogenation of the alkene to allow the preparation of the corresponding chiral 4- (1,1,1-trifluoropropan-2-yl) benzene-1-sulfonyl chlorides.

Scheme 6:

4- (1,1,1-Trifluoropropan-2-yl) benzene-1-sulfonyl chloride can also be prepared from commercially available 1-phenyl-ethanone 15 by a four-step process as shown in the scheme 6. The ketone can be converted into the trifluoromethyl hydroxyl intermediate by reaction with trimethyl-trifluoromethyl-silane (Journal of Organic Chemistry, 2000, 65, 8848-8856; Journal of Fluor Chemistry, 2003, 122, 243-246) which can be converted into trifluoromethyl bromide (Journal of the American Chemical Society, 1987, 109, 2435-4). Dehalogenation by catalytic hydrogenation (for example, Pd-C) can be followed by conversion of sulfonyl chloride by the methods described above.

Examples of solvents that can be used are ethers, such as diethyl ether, diisopropyl ether, methyl tert-butyl ether or tetrahydrofuran, aprotic polar solvents, such as dimethylformamide, dimethyl sulfoxide, dimethoxyethane and acetonitrile, aromatic hydrocarbons, such as toluene and xylene, ketones such as acetone methyl ethyl ketone, halohydrocarbons, such as dichloromethane, trichloromethane or dichloroethane, esters, such as ethyl acetate and methyl butyrate, carboxylic acids such as acetic acid or propionic acid, and alcohols such as methanol, ethanol, n-propanol, isopropanol , n-butanol, isobutanol, 2-butanol and tert-butanol.

If desired, a base may be present in order to neutralize the protons that are released in the reactions. Suitable bases include inorganic bases, such as sodium carbonate, potassium carbonate, sodium hydrogen carbonate or potassium hydrogen carbonate, and, in addition, alkoxides, such as sodium methoxide or sodium ethoxide, alkali metal hydrides, such as sodium hydride, and also organometallic compounds, such as butyllithium compounds or alkyl magnesium compounds, or organic nitrogen bases, such as triethylamine or pyridine. The latter compounds can at the same time serve as solvents.

The crude product is isolated in a customary manner, for example, by filtration, solvent distillation removal or reaction mixture extraction, etc. The resulting compounds can be purified in a customary manner, for example, by recrystallization of a solvent, by chromatography or by conversion into an acid addition salt.

Acidic addition salts are prepared in a usual manner by mixing the free base with the corresponding acid, when appropriate in solution in an organic solvent, for example, a lower alcohol, such as methanol, ethanol or propanol, an ether, such as methyl tert-butyl ether or diisopropylether, a ketone, such as acetone or methyl ethyl ketone, or an ester, such as ethyl acetate.

The compounds according to the invention of formula I are highly selective dopamine D3 receptor ligands, due to their low affinity for other receptors such as D1 receptors, D4 receptors, α1-adrenergic receptors and / or α2- adrenergic, muscarinergic receptors, histamine receptors, opiate receptors and, in particular, dopamine D2 receptors, leading to lower side effects than do the classic neuroleptics, which are antagonists of the D2 receptor. A compound of the invention can be a dopamine D3 receptor agonist, including partial agonistic activity or an antagonist of a D3 dopamine receptor, including partial antagonistic activity.

The high affinity of the compounds according to the invention for the D3 receptors is reflected in the very low receptor binding constants in vitro (Ki (D3) values) of as a rule less than 50 nm (nmol / l), preferably less 10 nM and, in particular, less than 5 nm. The displacement of [125I] -iodosuipride can, for example, be used in receptor binding studies to determine binding affinities for 15 D3 receptors.

The selectivity of the compounds according to the invention, that is, the ratio of Ki (D2) / Ki (D3) of the receptor binding constants, is as a rule at least 50, preferably at least 100, even better at least 150. The displacement of [3H] SCH23390, [125I] yodosulpride or [125I] espiperone can be used, for example, to carry out receptor binding studies on D1, D2 and D4 receptors. twenty

Due to their binding profile, the compounds can be used to treat diseases that respond to dopamine D3 receptor ligands (or that are susceptible to treatment with a dopamine D3 receptor ligand, respectively), that is, they are effective for treating those medical disorders or diseases in which exerting a (modular) influence on dopamine D3 receptors leads to an improvement in the clinical picture or for the disease to be cured. Examples of these diseases are disorders or diseases of the central nervous system.

Disorders or diseases of the central nervous system are understood as significant disorders that affect the spinal cord and, in particular, the brain. Within the meaning of the invention, the term "disorder" denotes disturbances and / or anomalies that are as a general rule seen as pathological conditions or functions that can manifest themselves in the form of particular signs, symptoms and / or malfunctions. While the treatment according to the invention can be directed towards individual disorders, that is, abnormalities or pathological conditions, it is also possible for several anomalies, which can be casuistically linked to each other, combined into patterns, that is, syndromes , which can be treated according to the invention.

The disorders that can be treated according to the invention are, in particular, psychiatric and neurological disturbances. These disturbances include, in particular, organic disturbances, which include symptomatic disturbances such as psychosis of the type of acute exogenous reaction or attention psychosis or of organic or exogenous causes, for example, in association with metabolic disturbances, infections and endocrinopathologies; endogenous psychoses, such as schizophrenia and schizotypal disturbances and hallucinations; affective disturbances, such as manic depressions and / or manic-depressive conditions, and also mixed forms of the aforementioned disturbances; neurotic and somatoform disturbances and also disturbances in association with stress; 40 dissociative disturbances, for example, loss of consciousness, turbidity in consciousness, double consciousness and personal disturbances; disturbances in attention and gait / sleep check, such as behavioral disturbances and emotional disturbances whose onset lies in childhood and youth, for example, hyperactivity in children, intellectual deficits, in particular attention disturbances (disorders attention deficit), memory disturbances and cognitive disturbances, for example, abnormal learning and memory 45 (abnormal cognitive function), dementia, narcolepsy and sleep disturbances, for example, restless legs syndrome, developmental disturbances; states of anxiety, delirium, disturbances in sexual life, for example, impotence in men; eating disturbances, for example anorexia or bulimia, addiction and other unspecified psychiatric disturbances.

Disorders that can be treated in accordance with the invention also include Parkinson's disease and epilepsy 50 and, in particular, affective disturbances related thereto.

Addiction diseases include psychic disorders and behavioral disturbances that are caused by the abuse of psychotropic substances, such as pharmaceuticals or narcotics, and also other addiction diseases, such as gambling addiction (unclassified impulse control control disorders somewhere else). Examples of addictive substances are: opioids (morphine, for example, heroin and codeine), cocaine; nicotine; alcohol, substances that interact with the GABA chloride channel complex, sedatives, hypnotics and tranquilizers, for example, benzodiazepines; LSD, cannabinoids; psychomotor stimulants, such as 3,4-methylenedioxy-N-methylamphetamine (ecstasy); amphetamine and amphetamine-like substances such as methylphenidate and other stimulants including

caffeine; Addictive substances that are particularly considered are opioids, cocaine, amphetamines or substances similar to amphetamine, nicotine and alcohol.

With regard to the treatment of addiction diseases, particular preference is given to those compounds according to the invention of formula I which themselves do not possess any psychotropic effect. This can also be observed in a test using rats, which, after receiving the administration of 5 compounds that can be used according to the invention, reduce their self-administration of psychotropic substances, for example cocaine.

In accordance with another aspect of the present invention, the compounds according to the invention are suitable for treating disorders whose causes can at least partially be attributed to the abnormal activity of dopamine D3 receptors. 10

In accordance with another aspect of the present invention, the treatment is directed, in particular, towards those disorders that can be influenced, within the meaning of expedited medicinal treatment, by linking exogenously administered binding patterns preferably (ligands) to dopamine D3 receptors.

Diseases that can be treated with the compounds according to the invention are often characterized by progressive development, that is, the conditions described above change over time; 15 As a general rule, the severity increases and the conditions may possibly merge with one another or other conditions may appear in addition to those that already exist.

The compounds according to the invention can be used to treat a large number of signs, symptoms and / or malfunctions that are related to disorders of the central nervous system and, in particular, with the aforementioned conditions. These signs, symptoms and / or malfunction include, for example, a disturbed relationship with reality, lack of discernment and ability to meet habitual social norms or demands made by life, changes in temperament, changes in individual behaviors, such as hunger, sleep, thirst, etc., and in the mood, disturbances in the ability to observe and combine, personality changes, in particular emotional flexibility, hallucinations, ego disturbances, distraction, ambivalence, autism, depersonalization and false perceptions, ideas from hallucinations, disjointed speech, lack of 25 synquinesia, walking in short steps, flexed posture of trunk and limbs, tremor, poverty of facial expression, monotonous speech, depressions, apathy, spontaneity and decision power impeded, ability of impoverished association, anxiety, nervous agitation, stuttering, social phobia, panic disturbances, symptoms of re shot in association with dependence, overt syndromes, states of excitement and confusion, dysphoria, dyskinetic syndromes and tics-like disorders, for example, Huntington's chorea and Gilles-de-la-Tourette syndrome, vertigo syndromes, for example, positional vertigo 30 peripheral, rotational and oscillatory, melancholy, hysteria, hypochondria and the like.

Within the meaning of the invention, a treatment also includes a preventive treatment (prophylaxis), in particular a relapsa prophylaxis or prophylaxis in phase, as well as treatment of signs, symptoms and / or poor chronic acute functions. The treatment can be symptomatically oriented, for example as symptom suppression. It can also be carried out for a short period, oriented to the medium term or it can be a long-term treatment, for example within the context of a maintenance therapy.

Therefore the compounds according to the invention are preferably suitable for the treatment of diseases of the central nervous system, in particular for treating affective disorders; neurotic disturbances, stress disturbances and somatoform disturbances and psychosis, and in particular, to treat schizophrenia and depression. Due to their high selectivity with respect to the D3 receptor, the compounds according to the invention are also suitable for treating renal function disturbances, in particular renal function disturbances that are caused by diabetes mellitus (see WO 00/67847 ) and, especially, diabetic nephropathy.

In particular, the compounds of the invention are suitable for treating the following disorders: Parkinson's disease, schizophrenia, cognitive disturbances, depression, anxiety, addiction, renal function disturbances, eating disturbances and epilepsy. Four. Five

Within the context of the treatment, the use according to the invention of the described compounds involves a method. In this method, an effective amount of one or more compounds, as a general rule formulated in accordance with pharmaceutical and veterinary practice, is administered to the individual to be treated, preferably a mammal, in particular a human being, a productive animal or A domestic animal. If such treatment is indicated, and in what form it will take place, it depends on the individual case and is subject to medical advice (diagnosis) that takes into consideration signs, symptoms and / or malfunctions that are present, the risks of developing signals , symptoms and / or particular malfunctions, and other factors.

As a general rule, the treatment is carried out by means of a simple or repeated daily administration, when appropriate together, or alternatively with other active compounds or preparations containing an active compound such as a daily dose of preferably from about 0.1 to 1000 mg / kg body weight, in 55

the case of oral administration, or from about 0.1 to 100 mg / kg of body weight, in the case of parenteral administration, which is given to an individual to be treated.

The invention also relates to the production of pharmaceutical compositions for treating an individual, preferably a mammal, in particular a human, productive animal or domestic animal. Thus, the ligands are usually administered in the form of pharmaceutical compositions comprising a pharmaceutically acceptable excipient together with at least one compound according to the invention and, where appropriate, other active compounds. These compositions can, for example, be administered orally, rectally, transdermically, subcutaneously, intravenously, intramuscularly or intranasally.

Examples of suitable pharmaceutical formulations are solid medicinal forms, such as powders, granules, tablets, in particular film tablets, dragees, sachets, sachets, sugar-coated tablets, capsules, such as hard gelatin capsules and soft gelatin capsules, vaginal suppositories or medicinal forms, semi-solid medicinal forms, such as ointments, creams, hydrogels, pastes or plasters, and also also liquid medicinal forms, such as solutions, emulsions, in particular oil-in-water emulsions, suspensions, for example lotions, preparations for injection and infusion preparations, and eye drops and ear drops. Implanted release devices can also be used to administer the inhibitors according to the invention. In addition, it is also possible to use liposomes or microspheres.

When the compositions are produced, the compounds according to the invention are optionally mixed or diluted with one or more excipients. The excipients may be solid, semi-solid or liquid materials that serve as vehicles, carriers or media for the active compound.

Suitable excipients are listed in specialist medical monographs. In addition, the formulations may comprise conventional pharmaceutically acceptable carriers or auxiliary substances, such as sliders; wetting agents, emulsifying and suspending agents; condoms; antioxidants; anti-irritants; chelating agents; coating aids; emulsion stabilizers; film formers; gel formers; odor masking agents; flavor correctors, resins, hydrocolloids, solvents, solubilizer; neutralizing agents; diffusion accelerators; pigments; quaternary ammonium compounds; re-greasing agents and 25 greasing agents; raw materials for ointments, creams or oils, silicone derivatives; spreading aids; stabilizers; sterilizers; suppository bases; tablet auxiliaries, such as binders, fillers, glidants, disintegrants or coatings; propellants; drying agents, opacifiers, thickeners, waxes, plasticizers and white mineral oils. A formulation in this regard is based on specialized knowledge as described, for example, in Fiedler, HP, Lexikon der Hilfsstoffe for Pharmazie, Kosmetik und 30 angrenzende Gebiete [Encyclopedia of auxiliary substances for pharmacy, cosmetics and related fields], 4th edition , Aulendorf: ECV-Editio Kantor-Verlag, 1996.

The following examples serve to explain the invention without limiting it.

The compounds were characterized by proton NMR in d6-dimethylsulfoxide or d-chloroform, if not otherwise established, in a 400 MHz or 500 MHz NMR instrument (Bruker ADVANCE), or by 35 mass spectrometry, in general , recorded through HPLC-MS in a rapid gradient on a C18 material (electrospray-ionization mode (ESI)), or melting point.

The nuclear magnetic resonance (NMR) spectral properties refer to chemical shifts (δ) expressed in parts per million (ppm). The relative area of displacements in the 1 H NMR spectrum corresponds to the number of hydrogen atoms for a particular functional type in the molecule. The nature of the displacement, 40 with respect to multiplicity, is indicated as singlet (s), wide singlet (s.br.), doublet (d), wide doublet (d br.), Triplet (t), wide triplet (t br.), quartet (q), quintet (quint.) and multiplet (m).

Preparation Examples

I. Intermediates

to. [2- (5-Amino-6-methoxy-pyridin-2-yloxy) -ethyl] -propyl- (acid) carbamic, tert-butyl ester 45

a.1 [2- (6-Methoxy-5-nitro-pyridin-2-yloxy) -ethyl] -propyl- (acid) carbamic, tert-butyl ester

A mixture of 6-bromo-2-methoxy-3-nitropyridine (5 g, 21.46 mmol), tert-butyl ester of (2-hydroxy-ethyl) -propyl-carbamic acid (4.36 g, 21.46 mmol) and K2CO3 (2.97 g, 21.46 mmol) in dimethylformamide (DMF) (60 ml) was stirred at room temperature for 24 hours and at 40 ° C for 4 hours. After evaporation of the solvent under reduced pressure the residue was purified by chromatography on silica gel with dichloromethane / methanol (10: 0, 9: 1, 7: 3, 0:10) as 50 eluent to provide 2.81 g (36.9%) of the product.

MS (ESI) m / z: 356.25 [M + H (-BOC)] +

a.2 [2- (5-Amino-6-methoxy-pyridin-2-yloxy) -ethyl] -propyl- (acid) carbamic acid, tert-butyl ester

A mixture of [2- (6-methoxy-5-nitro-pyridin-2-yloxy) -ethyl] -propyl- (acid) carbamic acid, tert-butyl ester (1.12 g, 3.16 mmol) and 10% palladium on carbon (0.34 g, 0.316 mmol in ethanol (80 ml) was hydrogenated at atmospheric pressure until hydrogen consumption was complete. After filtration and evaporation of the solvent under reduced pressure, 960 mg (93.5% of the title compound was obtained. 5

MS (ESI) m / z: 326.25 [M + H] +

b. 6- (1-Benzyl-Dyrrolidin-3-yloxy) -2-methoxy-pyridin-3-ylamine

b.1 6- (1-Benzyl-pyrrolidin-3-yloxy) -2-methoxy-3-nitro-pyridine

A mixture of 6-bromo-2-methoxy-3-nitropyridine (1.5 g, 6.44 mmol), 1-benzyl-pyrrolidin-3-ol (1.14 g, 6.44 mmol) and K2CO3 (0.89 g, 6.44 mmol) in dimethylformamide ( DMF) (20 ml) was stirred at room temperature for 24 hours and at 40 ° C for 4 hours. After evaporation of the solvent under reduced pressure the residue was purified by silica gel chromatography with dichloromethane / methanol (10: 0, 9: 1, 7: 3, 0:10) as eluent to provide 380 mg (18.1%) of the product.

MS (ESI) m / z: 330.15 [M + H] +

b.2 6- (1-Benzyl-pyrrolidin-3-yloxy) -2-methoxy-pyridin-3-ylamine

To a solution of 6- (1-benzyl-pyrrolidin-3-yloxy) -2-methoxy-3-nitro-pyridine (0.38 g, 1.15 mmol) in acetic acid (4 ml) at 80 ° C was added iron (0.32 g, 5.77 mmol) slowly in portions. The exothermic reaction was stirred for 3 hours at 80 ° C. After evaporation of the solvent under reduced pressure the solid residue was dissolved in 1N NaOH, which was extracted 6 times with dichloromethane. The combined organic layers were dried over MgSO4, filtered and the solvent evaporated to obtain 240 mg (68.9%) of the title compound. twenty

MS (ESI) m / z: 300.15 [M + H] +

C. 2-Methoxy-6- (2-pyrrolidin-1-yl-ethoxy) -oyridin-3-ylamine

The desired product was obtained following the analogous synthetic procedure described in the preparation of intermediates a. starting from 6-bromo-2-methoxy-3-nitropyridine and 2-pyrrolidin-1-yl-ethanol.

MS (ESI) m / z: 268.15 [M + H] + 25

d. [2- (5-Amino-4-methoxy-pyrimidin-2-yloxy) -ethyl] -propyl- (acid) carbamic, tert-butyl ester

d.1 2-Chloro-4-methoxy-5-nitro-pyrimidine

To a solution of 2,4-dichloro-5-nitropyrimidine (10 g, 51.55 mmol) in methanol (150 ml) at -10 ° C was added a solution of potassium methanolate (3.62 g, 51.55 mmol) in methanol (150 ml) over a period of 10 minutes. The mixture was allowed to warm to 0 ° C and the solvent was evaporated under reduced pressure at 30 ° C. The residue was purified by silica gel chromatography with n-heptane ethyl acetate (3: 1) as eluent yielding 3.7 g (37.9%) of the title compound. 1.34 g (13.7%) of 4-chloro-2-methoxy-5-nitropyrimidine were obtained as collateral product.

MS (ESI) m / z: 196.15 [M + H] +

d.2 [2- (4-Methoxy-5-nitro-pyrimidin-2-yloxy) -ethyl] -propyl- (acid) carbamic, tert-butyl ester

To a solution of tert-butyl ester of (2-hydroxy-ethyl) -propyl-carbamic acid (1.07 g, 5.28 mmol) in THF (40 ml) at 0 ° C was added NaH (0.25 g, 5.80 mmol). After stirring the suspension at 0 ° C for 30 minutes a solution of 2-chloro-4-methoxy-5-nitropyrimidine (1 g, 5.28 mmol) in THF (10 ml) was added and the mixture was stirred at room temperature for 16 hours . The mixture was added to water, which was extracted three times with dichloromethane. The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure to obtain the title compound. 40

MS (ESI) m / z: 357.15 [M + H] +

d.3 [2- (5-Amino-4-methoxy-pyrimidin-2-yloxy) -ethyl] -propyl- (acid) carbamic, tert-butyl ester

To a mixture of [2- (4-methoxy-5-nitro-pyrimidin-2-yloxy) -ethyl] -propyl (acid) carbamic acid, tert-butyl ester (1.76 g, 4.94 mmol) crude and 10% palladium on carbon (200 mg) in water (15 ml) was slowly added a solution of formate of

ammonium (3.12 g, 49.44 mmol) in water (10 ml) at 80 ° C. After stirring for 1 hour at 80 ° C the mixture was filtered and concentrated under reduced pressure. The aqueous layer was extracted three times with dichloromethane. The combined organic layers were dried over MgSO4, filtered and the solvent was evaporated under reduced pressure. The residue was purified by chromatography on silica gel with toluene / THF / MeOH (4: 1: 1) / 2.5% triethylamine to give 720 mg (44.7%) of the title compound. 5

MS (ESI) m / z: 327.15 [M + H] +

and. 6- (2-Dimethylamino-ethoxy) -pyridin-3-viamine

The desired product was obtained following the synthetic procedure analogous to that described for the preparation of intermediate a., Starting from 2-chloro-5-nitropyridine and 2-dimethylaminoethanol.

MS (ESI) m / z: 182.15 [M + H] + 10

F. [2- (5-Amino-pyridin-2-yloxy) -ethyl] -propyl- (acid) carbamic, tert-butyl ester

The desired product was obtained following the synthetic procedure analogous to that described for the preparation of intermediate a. starting from 2-chloro-5-nitropyridine and (2-hydroxy-ethyl) -propyl- (acid) carbamic acid, tert-butyl ester.

MS (ESI) m / z: 326.15 [M + H] +

g. 4 - ((S) -2-Fluoro-1-methyl-ethyl) benzenesulfonyl chloride 15

g.1 Toluene-4-sulfonic acid (S) -2-phenyl-propyl ester

To a solution of 20 g of (S) - (-) - 2-phenyl-1-propanol in 240 ml of dichloromethane 28 g of p-toluenesulfonyl chloride (146.8 mmol) were added portionwise. After stirring for 18 hours at room temperature, the organic phase was washed with 100 ml of water, dried over magnesium sulfate, filtered, and the solvent was evaporated under reduced pressure to yield 43 g of the title compound. twenty

1H-NMR (CDCl3, 400 MHz): δ [ppm] 7.65 (d, 2H), 7.15-7.3 (m, 5H), 7.1 (d, 2H), 4.0-4.1 (m, 2H), 3.1 (m, 1H), 2.4 (s, 3H), 1.3 (d, 3H).

g.2 ((S) -2-Fluoro-1-methyl-ethyl) -benzene

9.62 g of (S) -2-phenyl-propyl ester of toluene-4-sulfonic acid (33.13 mmol) was dissolved in 80 ml of polyethylene glycol 400. 9.62 g of potassium fluoride (165.6 mmol) was added and the reaction mixture stirred at 50 ° C for 3 days and another 2 days at 55-70 ° C. The reaction was treated with 150 ml of saturated aqueous sodium chloride solution, extracted three times with diethyl ether, and the combined organic layers were dried over magnesium sulfate, filtered and the solvent was evaporated under reduced pressure. The crude product was purified through silica gel chromatography, using 15% cyclohexane / ethyl acetate as eluent. 2.85 g of the desired product, containing 25% of the collateral removal product, was isolated. 30

1H-NMR (CDCl3, 400 MHz): δ [ppm] 7.2-7.4 (m, 5H), 4.3-4.6 (several m, 2H), 3.15 (m, 1H). 1.3 (m, 3H).

g.3 4 - ((S) -2-Fluoro-1-methyl-ethyl) -benzenesulfonyl chloride

3.5 g of ((S) -2-fluoro-l-methyl-ethyl) -benzene (25.32 mmol) was dissolved in 80 ml of dichloromethane. At 0-5 ° C, 11.81 g of chlorosulfonic acid (101.31 mmol) dissolved in 20 ml of dichloromethane were added dropwise. The reaction mixture was stirred for 30 minutes at room temperature and 2 hours at 30 ° C. The solvent was evaporated. 150 ml of diethyl ether was added to the residue, washed once with 150 ml of water, and the organic layer was dried over magnesium sulfate, filtered, and the solvent was evaporated under reduced pressure. The crude product was purified by chromatography on silica gel with n-heptane-dichloromethane (6: 4) as eluent to give 1.5 g of the title compound.

1H-NMR (CDCl3, 400 MHz): δ [ppm] 8.0 (d, 2H), 7.5 (d, 2H), 4.5 (dd, 2H), 3.25 (m, 1H), 1.4 (d, 3H). 40

h. 4 - ((R) -2-Fluoro-1-methyl-ethyl) -benzenesulfonyl chloride

h.1 Toluene-4-sulfonic acid (R) -2-phenyl-propyl ester

Following the procedure analogous to that used for the synthesis of toluene-4-sulfonic acid (S) -2-phenyl-propyl ester, but using (R) -2-phenyl-1-propanol as the starting compound, the compound of the Title.

h.2 ((R) -2-Fluoro-1-methyl-ethyl) -benzene

The title compound was prepared as described above for the synthesis of ((S) -2-ftuoro-1-methyl-ethyl) -benzene, but using toluene-4-sulfonic acid (R) -2-phenyl-propyl ester instead of toluene-4-sulfonic acid (S) -2-phenylpropyl ester.

1H-NMR (CDCl3, 400 MHz): δ [ppm] 7.2-7.4 (m, 5H), 4.3-4.6 (several m, 2H), 3.15 (m, 1H) .1.3 (m, 3H).

h.3 4 - ((R) -2-Fluoro-1-methyl-ethyl) -benzenesulfonyl chloride 5

1.3 g of ((R) -2-fluoro-1-methyl-ethyl) -benzene (9.4 mmol) were dissolved in 50 ml of dichloromethane. 1.1 g of chlorosulfonic acid (9.4 mmol) dissolved in 10 ml of dichloromethane were added dropwise at 0-5 ° C. The reaction mixture was stirred for 20 minutes at 0-5 ° C and then added to a solution of 2.15 g of phosphorus pentachloride dissolved in 40 ml of dichloromethane. The reaction mixture was stirred for 30 minutes at 0-5 ° C and for 1 hour at room temperature. The solvent was evaporated, 100 ml of diethyl ether was added, the mixture was washed once with 150 ml of water, and the organic layer was dried over magnesium sulfate, filtered and the solvent was evaporated under reduced pressure. The crude product was purified by silica gel chromatography with n-heptane-dichloromethane (1: 1) as eluent to give 0.261 g of the title compound.

1H-NMR (CDCl3, 400 MHz): δ [ppm] 8.0 (d, 2H), 7.5 (d, 2H), 4.5 (dd, 2H), 3.25 (m, 1H), 1.4 (d, 3H).

i. 4- (2-Fluoro-1-methyl-ethyl) -benzenesulfonyl chloride

Following the procedures analogous to that used for the preparation of 4 - ((S) -2-fluoro-1-methyl-ethyl) -benzenesulfonylchloride, but starting from 2-phenyl-1-propanol in step a.3.g.1, the title compound was prepared.

1H-NMR (CDCl3, 400 MHz): δ [ppm] 8.0 (d, 2H), 7.5 (d, 2H), 4.5 (dd, 2H), 3.25 (m, 1H), 1.4 (d, 3H).

k. 4- (3-Fluoropropyl) -benzenesulfonyl chloride

k.1 (3-Fluoropropyl) -benzene 20

15.6 g of diethylaminosulfurtrifluoride (DAST, 96.91 mmol) was dissolved in 18 ml of dichloromethane. At 0-5 ° C, 12 g of 3-phenyl-1-propanol (88.1 mmol) dissolved in 30 ml of dichloromethane were added dropwise. The reaction mixture was stirred for 18 hours, and, after the addition of 30 ml of dichloromethane, was poured onto 100 ml of ice water. The organic layer was separated, dried over magnesium sulfate, filtered and the solvent was evaporated. The crude product was purified by distillation at a bath temperature of 106 ° C to 20 mm to yield 7.4 g of the title compound.

1H-NMR (CDCl3, 400 MHz): δ [ppm] 7.1-7.3 (m, 5H), 4.4 (dt, 2H), 2.7 (m, 2H) .2.0 (m, 2H).

k.2 4- (3-Fluoropropyl) -benzenesulfonyl chloride

4.1 g of (3-fluoro-propyl) -benzene (29.67 mmol) was dissolved in 40 ml of dichloromethane. 6.91 g of chlorosulfonic acid (59.34 mmol), dissolved in 10 ml of dichloromethane, were added dropwise at 0-5 ° C. The reaction mixture was stirred for 45 minutes at 0-5 ° C and then added to a solution of 6.8 g of phosphorus pentachloride (32.63 mmol) dissolved in 50 ml of dichloromethane. The reaction mixture was stirred for 1 hour at 5-10 ° C. The solvent was evaporated, 150 ml of diethyl ether was added, the solution was washed once with 150 ml of ice and water mixture, and the organic layer was dried over magnesium sulfate, filtered and the solvent was evaporated under reduced pressure. The crude product was purified by silica gel chromatography with n-heptane-dichloromethane (11: 9) as eluent to give 5.5 g of the title compound.

1H-NMR (CDCl3, 400 MHz): δ [ppm] 7.95 (d, 2H), 7.45 (d, 2H), 4.5 (dt, 2H), 2.9 (t, 2H), 2.05 (m, 2H).

m. 4- (2-Fluoroethyl) -benzenesulfonyl chloride

m.1 (2-Fluoroethyl) -benzene

6.8 g of the title compound were obtained from commercially available 2-phenyl-ethanol following the procedure used for the synthesis of (3-fluoropropyl) -benzene.

1H-NMR (CDCl3, 400 MHz): δ [ppm] 7.1-7.3 (m, 5H), 4.6 (m, 1H), 4.45 (m, 1H), 2.95 (m, 1H), 2.9 (m, 1H) .

m.2 4- (2-Fluoroethyl) -benzenesulfonyl chloride

3.55 g were obtained following the procedure used for the synthesis of 4 - ((R) -2-fluoro-1-methyl-ethyl) -benzenesulfonyl chloride.

1H-NMR (CDCl3, 400 MHz): δ [ppm] 8.0 (d, 2H), 7.5 (d, 2H), 4.7 (dt, 2H), 3.05-3.2 (dt, 2H).

n. 4- (1,1,1-Trifluoropropan-2-yl) benzenesulfonyl chloride and 2- (1,1,1-trifluoropropan-2-yl) benzenesulfonyl chloride

Prepared on a scale of 14 g following the procedure outlined in Scheme 5. 2- (1,1,1-Trifluoropropan-2-5 yl) benzenesulfonyl chloride is a byproduct of the reaction.

4- (1,1,1-Trifluoropropan-2-yl) benzenesulfonyl chloride:

MS (ESI) m / z: 273.1 [M + H] +

1H-NMR (DMSO-d6): δ [ppm] 7.62 (d, 2H), 7.33 (d, 2H), 3.81 (m, 1H), 1.42 (d, 3H).

2- (1,1,1-Trifluoropropan-2-yl) benzenesulfonyl chloride: 10

MS (ESI) m / z: 273.1 [M + H] +

or. 4-Oxazol-4-yl-benzenesulfonyl chloride

A solution of 2-bromo-1-phenyl-ethanone (40 g, 201 mmol) and ammonium formate (44.35 g, 703 mmol) in formic acid (75 ml) were heated at reflux for 2 hours. The reaction mixture was evaporated under reduced pressure, and the residue was added to water, which was extracted three times with dichloromethane. The crude product was purified by silica gel chromatography using ethyl acetate / heptane (0:10, 1: 9) as eluent. At 0 ° C, 4-p-phenyloxazole (3 g, 20.67 mmol) was added slowly to 24.08 g of chlorosulfonic acid (206.67 mmol). The reaction mixture was stirred for 20 minutes at 0-5 ° C and then heated to room temperature, and finally stirred at 45 ° C for 2 hours. The reaction mixture was then carefully added (!) To ice water mixture. The precipitate was filtered, washed with water and dried in a vacuum oven at 30 ° C to give the title compound (4.3 g, 76.8%). twenty

MS (ESI) m / z: 240.15 [M + H] +

(4-Oxazol-4-yl-benzenesulfonic acid methyl ester)

p. 6- [2- (Benzyl-propyl-amino) -ethoxy] -2-methoxy-pyridin-3-ylamine

p.1 Benzyl- [2- (6-methoxy-5-nitro-pyridin-2-yloxy) -ethyl] -propyl-amine

To a mixture of Pd (OAc) 2 (112 mg, 0.5 mmol) and [1,1 '] binaphthalen-2-yl-di-tert-butyl phosphate (30 mg, 0.75 mmol) in toluene 25 (40 ml) 6-Bromo-2-methoxy-3-pyridine (2.92 g, 12.54 mmol), Cs2CO3 (20.4 g, 62.68 mmol), and 2- (benzyl-propyl-amino) -ethanol (3.63 g, 18.8 mmol) were added. The mixture was stirred under nitrogen at room temperature for 24 hours. After evaporation of the solvent under reduced pressure, the residue was dissolved in water and extracted five times with dichloromethane. The residue was purified by silica gel chromatography with n-heptane / dichloromethane (10: 0, 7: 3, 0:10) as eluent to provide 2.92 g (67.3%) of the product. 30

MS (ESI) m / z: 346.15 [M + H] +

p.2 6- [2- (Benzyl-propyl-amino) -ethoxy] -2-methoxy-pyridin-3-ylamine

To a solution of benzyl- [2- (6-methoxy-5-nitro-pyridin-2-yloxy) -ethyl] -propylamine (2.92 g, 8.45 mmol) in acetic acid (120 ml) at 80 ° C was added iron (2.36 g 42.27 mmol) slowly in portions. The exothermic reaction was stirred for 2 hours at 80 ° C. After evaporation of the solvent under reduced pressure, the solid residue was dissolved in aqueous NaHCO3. Which was extracted 6 times with dichloromethane. The residue was purified by silica gel chromatography with dichloromethane / methanol (10: 0; 8: 2; 6.5: 3.5; 0:10) as eluent to provide 1.4 g (52.5%) of the product.

MS (ESI) m / z: 316.15 [M + H] +

q. (S) -2- (5-Amino-6-methoxy-pyridin-2-yloxymethyl) -pyrrolidine-1- (acid) carboxylic tert-butyl ester

q.1 (S) -2- (6-Methoxy-5-nitro-pyridin-2-yloxymethyl) -pyrrolidine-1- (acid) carboxylic tert-butyl ester 40

To a mixture of Pd (OAc) 2 (0.08 g, 0.34 mmol) and [1,1 '] binaphthalen-2-yl-di-tert-butyl phosphate (0.14 g, 0.34 mmol) in toluene (10 ml) is added 6-bromo-2-methoxy-3-nitropyridine (1.0 g, 4.29 mmol), Cs2CO3 (3.5 g, 10.73 mmol), and (S) -2-hydroxymethyl-

pyrrolidine-1- (acid) carboxylic tert-butyl ester (1.73 g, 8.58 mmol). The mixture was stirred under nitrogen at room temperature for 24 hours. After evaporation of the solvent under reduced pressure, the residue was purified by silica gel chromatography with dichloromethane / ethyl acetate / methanol (10: 0: 0; 9: 0.5: 0.5; 7: 1.5: 1.5; 0: 5: 5) as eluent to provide 0.11 g (7.5%) of the product.

MS (ESI) m / z: 354.15 [M + H] + 5

q.2 (S) -2- (5-Amino-6-methoxy-pyridin-2-yloxymethyl) -pyrrolidine-1- (acid) carboxylic tert-butyl ester

A solution of (S) -2- (6-methoxy-5-nitro-pyridin-2-yloxymethyl) -pyrrolidine-1- (acid) carboxylic tert-butyl ester (0.11 g, 0.32 mmol) in methanol (11 ml) was hydrogenated using the ThalesNano H-Cube® hydrogenation reactor using a 10% palladium on carbon catalyst cartridge. After concentration of the solution under reduced pressure, 0.10 g (92.6%) of the title compound were obtained. 10

MS (ESI) m / z: 324.15 [M + H] +

r. (R) -2- (5-Amino-6-methoxy-pyridin-2-yloxymethyl) -pyrrolidine-1- (acid) carboxylic tert-butyl ester

The desired product was obtained following the synthetic procedure analogous to that described for the preparation of intermediate q starting from 6-bromo-2-methoxy-3-nitropyridine and (R) -2-hydroxymethyl-pyrrolidine-1- (acid) carboxylic tert- butyl ester. fifteen

MS (ESI) m / z: 324.15 [M + H] +

s. (S) -2- (5-Amino-6-methyl-pyridin-2-yloxymethyl) -pyrrolidine-1- (acid) carboxylic tert-butyl ester

The desired product was obtained following the synthetic procedure analogous to that described for the preparation of intermediate q starting from 6-chloro-2-methyl-3-nitropyridine and (S) -2-hydroxymethyl-pyrrolidine-1- (acid) carboxylic tert- butyl ester. twenty

MS (ESI) m / z: 340.15 [M + H] +

t. (R) -2- (5-Amino-6-methyl-pyridin-2-yloxymethyl) -pyrrolidine-1- (acid) carboxylic tert-butyl ester

The desired product was obtained following the synthetic procedure analogous to that described for the preparation of intermediate q starting from 6-chloro-2-methyl-3-nitro-pyridine and (R) -2-hydroxymethyl-pyrrolidine-1- (acid) carboxylic acid tert-butyl ester. 25

MS (ESI) m / z: 340.15 [M + H] +

or. [2- (5-Amino-6-methyl-pyridin-2-yloxy) -ethyl] -propyl- (acid) carbamic acid, tert-butyl ester

u.1 [2- (6-Methyl-5-nitro-pyridin-2-yloxy) -ethyl] -propyl- (acid) carbamic, tert-butyl ester

A mixture of 6-chloro-2-methyl-3-nitro-pyridine (1 g, 5.79 mmol), tert-butyl ester of (2-hydroxyethyl) -propyl-carbamic acid (1.18 g, 5.79 mmol) and lithium hydride (0.05 g, 6.37 mmol) in toluene (5 ml) was stirred at 90 ° C for 4 hours. After evaporation of the solvent under reduced pressure the residue was purified by silica gel chromatography with heptane / ethyl acetate (10:00; 08:02; 0:10) as eluent to provide 1.38 g (70.2%) of the product .

MS (ESI) m / z: 284.15 [M + H (- [tert-butyl])] +

u.2 [2- (5-Amino-6-methyl-pyridin-2-yloxy) -ethyl] -propyl- (acid) carbamic acid, tert-butyl ester

A solution of [2- (6-methyl-5-nitro-pyridin-2-yloxy) -ethyl] -propyl- (acid) carbamic, tert-butyl ester (300 mg, 0.88 mmol) in methanol (10 ml) was hydrogenated using the ThalesNano H-Cube® hydrogenation reactor using a 10% palladium catalyst cartridge in carbon. After concentration of the solution under reduced pressure, 230 mg / 84.2% of the title compound was obtained.

v. 6- [2- (Benzyl-propyl-amino) -ethoxy] -2-methyl-pyridin-3-ylamine

The desired product was obtained following the synthetic procedure analogous to that described for the preparation of intermediate p starting from 6-chloro-2-methyl-3-nitropyridine and 2- (benzyl-propyl-amino) -ethanol.

MS (ESI) m / z: 300.15 [M + H] +

w. 6- [2- (Benzyl-propyl-amino) -ethoxy] -4-methyl-pyridin-3-ylamine

The desired product was obtained following the synthetic procedure analogous to that described for the preparation of intermediate p starting from 2-chloro-4-methyl-5-nitropyridine and 2- (benzyl-propyl-amino) -ethanol.

MS (ESI) m / z: 300.15 [M + H] +

x. 6- [2- (Benzyl-propyl-amino) -ethoxy] -5-methyl-pyridin-3-ylamine 5

The desired product was obtained following the synthetic procedure analogous to that described for the preparation of intermediate p starting from 2-bromo-3-methyl-5-nitropyridine and 2- (benzyl-propyl-amino) -ethanol.

MS (ESI) m / z: 300.15 [M + H] +

Y. 4- (2-Fluoro-ethoxy) -benzenesulfonylchloride

At 0 ° C, (2-fluoro-ethoxy) -benzene (20 mmol) was added slowly to chlorosulfonic acid (200 mmol). The reaction mixture was stirred for 20 minutes at 0-5 ° C and then heated to room temperature, and finally stirred at 45 ° C for 2 hours. Then the reaction mixture was carefully added (!) To ice water. The precipitate was filtered, washed with water and dried in a vacuum oven at 30 ° C to give the title compound.

1H-NMR (CDCl3): δ [ppm] 4.21-4.45 (m, 2H), 4.65-5.00 (m, 2H), 7.08 (d, 2H), 8.00 (d, 2H).

z. 4- (2,2-Difluoro-ethoxy) -benzenesulfonylchloride 15

The desired product was obtained following the synthetic procedure analogous to that described for the preparation of intermediate and.

1H-NMR (CDCl3): δ [ppm] 4.21-4.40 (m, 2H), 5.82-6.45 (m, 1H), 7.08 (d, 2H), 8.02 (d, 2H).

zz. 4- (2,2,2-Trifluoro-ethoxy) -benzenesulfonylchloride

The desired product was obtained following the synthetic procedure analogous to that described for the preparation of intermediate and.

1H-NMR (CDCl3): δ [ppm] 4.40-4.55 (m, 2H), 7.10 (d, 2H), 8.02 (d, 2H).

II. Preparation of compounds I

EXAMPLE 1

4- (3-Fluoro-propyl) -N- [2-methoxy-6- (2-propylamino-ethoxy) -pyridin-3-yl] -benzenesulfonamide x HCl 25

After a solution of [2- (5-amino-6-methoxy-pyridin-2-yloxy) -ethyl] -propyl-carbamic acid tert-bityl ester (200 mg, 0.62 mmol) in pyridine (3 ml) was stirred at room temperature for 30 minutes, 4- (3-fluoro-propyl) -benzenesulfonyl chloride (160 mg, 0.68 mmol) was added. The mixture was stirred at room temperature for 16 hours after which the solvent was evaporated under reduced pressure. The residue was taken in toluene and the solvent was evaporated again. This procedure was repeated once. The residue was purified by chromatography on silica gel 30 with n-hexane / ethyl acetate (1: 0; 1: 1; 0: 1) /0.2% of triethylamine as eluent. The residue was dissolved in dichloromethane (5 ml). At 0 ° C HCl in diethyl ether (1 ml) was added to this solution. The mixture was stirred at room temperature for 6 hours. After concentration under reduced pressure, the residue was purified by chromatography (Cromabond-C18) with H2O / acetonitrile (95: 5; 0: 100; 95: 5) /0.1% acetic acid as eluent. The oil solution thus obtained in 1N NaOH was extracted 3 times with dichloromethane (45 ml). The combined organic layers were concentrated to 30 ml and HCl in diethyl ether (2 ml) was added. The solid formed was filtered dried in a vacuum oven to obtain 88.9 mg (35.6%) of the title compound.

MS (ESI) m / z: 426.25 [M + H] +

1H-NMR (MeOD): δ [ppm] 7.70 (m, 1H), 7.60 (d, 2H), 7.35 (d, 2H), 6.45 (d, 1H), 4.50-4.60 (m, 2H), 4.35- 4.50 (m, 2H), 3.60 (s, 3H), 3.40-3.45 (m, 2H), 3.00-3.10 (m, 2H), 2.75-2.80 (m, 2H), 1.90-2.10 (m, 2H), 1.70-1.85 (m, 2H), 1.05 (t, 3H). 40

EXAMPLE 2

N- (2-Methoxy-6- (2-propylamino-ethoxy) -pyridin-3-yl] -4-trifluoromethoxy-benzenesulfomide x HCl

The desired product was obtained following the synthetic procedure analogous to that described for example 1 starting from [2- (5-Amino-6-methoxy-pyridin-2-yloxy) -ethyl] -propyl- (acid) carbamic acid, tert-ester butyl and 4-trifluoromethoxybenzenesulfonyl chloride.

MS (ESI) m / z: 449.25 [M + H] +

1H-NMR (D6-DMSO): δ [ppm] 7.75 (d, 2H), 7.56 (d, 2H), 7.45 (d, 1H), 6.30 (d, 1H), 4.15-4.25 (m, 2H), 3.40 (s, 3H), 2.80-5 2.90 (m, 2H), 2.50-2.55 (m, 2H), 1.35-1.45 (m, 2H), 0.85 (t, 3H).

EXAMPLE 3

N- [2-Methoxy-6- (2-propylamino-ethoxy) -pyridin-3-yl] -4- (2,2,2-trifluoro-1-methylethyl) -benzenesulfonamide x HCl

The desired product was obtained following the synthetic procedure analogous to that described for example 1 starting from [2- (5-Amino-6-methoxy-pyridin-2-yloxy) -ethyl] -propyl- (acid) carbamic acid, tert-ester butyl and 4- (2,2,2-trifluoro-1-methyl-ethyl) -10 benzenesulfonyl chloride.

MS (ESI) m / z: 462.15 [M + H] +

1H-NMR (CDCl3): δ [ppm] 9.90 (br., 2H), 7.70 (d, 1H), 7.65 (d, 2H), 7.40 (d, 2H), 6.45 (d, 1H), 4.60- 4.70 (m, 2H), 3.55 (s, 3H), 3.35-3.50 (m, 1H), 3.30-3.35 (m, 2H), 2.95-3.05 (m, 2H), 1.90-2.00 (m, 2H), 1.50 (d, 3H), 0.95 (t, 3H).

EXAMPLE 4 15

4-Isopropyl-N- [2-methoxy-6- (2-propylamino-ethoxy) -pyridin-3-yl] -benzenesulfonamide x HCl

The desired product was obtained following the synthetic procedure analogous to that described for example 1 starting from [2- (5-Amino-6-methoxy-pyridin-2-yloxy) -ethyl] -propyl- (acid) carbamic acid, tert-ester butyl and 4-Isopropyl-benzenesulfonyl chloride.

MS (ESI) m / z: 408.25 [M + H] + 20

EXAMPLE 5

4-Difluoromethoxy-N- [2-methoxy-6- (2-propylamino-ethoxy) -pyridin-3-yl] -benzenesulfonamide x HCl

The desired product was obtained following the synthetic procedure analogous to that described for example 1 starting from [2- (5-Amino-6-methoxy-pyridin-2-yloxy) -ethyl] -propyl- (acid) carbamic acid, tert-ester butyl and 4-difluoromethoxybenzenesulfonyl chloride. 25

MS (ESI) m / z: 432.15 [M + H] +

1H-NMR (MeOD): δ [ppm] 7.70-7.80 (m, 3H), 7.25 (d, 2H), 7.70 (t, 1H), 6.45 (d, 1H), 4.50-4.55 (m, 2H), 3.60 (s, 3H), 3.40-3.45 (m, 2H), 3.00-3.10 (m, 2H), 1.70-1.85 (m, 2H), 1.05 (t, 3H).

EXAMPLE 6

4- (2-Fluoro-ethyl) -N- [2-methoxy-6- (2-propylamino-ethoxy) -pyridin-3-yl] -benzenesulfonamide x HCl 30

The desired product was obtained following the synthetic procedure analogous to that described for example 1 starting from [2- (5-Amino-6-methoxy-pyridin-2-yloxy) -ethyl] -propyl- (acid) carbamic acid, tert-ester butyl and 4- (2-fluoroethyl) -benzenesulfonyl chloride.

MS (ESI) m / z: 412.25 [M + H] +

1H-NMR (D6-DMSO): δ [ppm] 9.45 (br., 3H), 7.55 (d, 2H), 7.40-7.50 (m, 3H), 7.10 (d, 2H), 6.40 (d, 1H ), 4.60-4.75 (m, 35

2H), 4.45-4.55 (m, 2H), 3.50 (s, 3H), 3.20-3.30 (m, 2H), 3.00-3.10 (m, 2H), 2.85 (t, 2H), 1.65-1.75 (m, 2H), 0.90 (t, 3H).

EXAMPLE 7

N- [2-Methoxy-6- (2-propylamino-ethoxy) -pyridin-3-yl] -4-oxazol-5-yl-benzenesulfonamide x HCl

The desired product was obtained following the synthetic procedure analogous to that described for example 1 starting from [2- (5-Amino-6-methoxy-pyridin-2-yloxy) -ethyl] -propyl- (acid) carbamic acid, tert-ester butyl and 4-oxazol-5-ylbenzenesulfonyl chloride.

MS (ESI) m / z: 433.25 [M + H] +

1H-NMR (MeOD): δ [ppm] 8.35 (s, 1H), 7.85 (d, 2H), 7.80 (d, 2H), 7.70-7.75 (m, 3H), 6.45 (d, 1H), 4.50- 4.55 (m, 2H), 5 3.60 (s, 3H), 3.40-3.45 (m, 2H), 3.00-3.05 (m, 2H), 1.60-1.70 (m, 2H), 1.05 (t, 3H).

EXAMPLE 8

4- (2-Fluoro-ethoxy) -N- [2-methoxy-6- (2-propylamino-ethoxy) -pyridin-3-yl] -benzenesulfonamide x HCl

The desired product was obtained following the synthetic procedure analogous to that described for example 1 starting from [2- (5-Amino-6-methoxy-pyridin-2-yloxy) -ethyl] -propyl- (acid) carbamic acid, tert-ester butyl and 4- (2-Fluoroethoxy) -benzenesulfonyl chloride.

MS (ESI) m / z: 428.10 [M + H] +

1H-NMR (D6-DMSO): δ [ppm] 9.40 (s, 1H), 9.25 (s br., 2H), 7.60 (d, 2H), 7.45 (d, 1H), 7.10 (d, 2H), 6.35 (d, 1H), 4.75 (d, 2H), 4.50 (m, 2H), 4.30 (d, 2H), 3.55 (s, 3H), 3.25 (s br., 2H), 2.85 (s br., 2H), 1.60-1.70 (m, 2H), 0.90 (t, 3H).

EXAMPLE 9 15

4- (2,2-Difluoro-ethoxy) -N- [2-methoxy-6- (2-propylamino-ethoxy) -pyridin-3-yl] -benzenesulfonamide x HCl

The desired product was obtained following the synthetic procedure analogous to that described for example 1 starting from [2- (5-Amino-6-methoxy-pyridin-2-yloxy) -ethyl] -propyl- (acid) carbamic acid, tert-ester butyl and 4- (2,2-Difluoroethoxy) -benzenesulfonyl chloride.

MS (ESI) m / z: 446.05 [M + H] + 20

1H-NMR (D6-DMSO): δ [ppm] 9.40 (s, 1H), 9.15 (s br., 2H), 7.60 (d, 2H), 7.45 (d, 1H), 7.15 (d, 2H), 6.40 (t, 1H), 6.39 (d, 1H), 4.47 (m, 2H), 4.40 (t, 2H), 3.55 (s, 3H), 3.25 (s br., 2H), 2.88 (s br., 2H), 1.60-1.70 (m, 2H), 0.90 (t, 3H).

EXAMPLE 10

N- [2-Methoxy-6- (2-propylamino-ethoxy) -pyridin-3-yl] -4- (2,2,2-trifluoro-ethoxy) -benzenesulfonamide x HCl

The desired product was obtained following the synthetic procedure analogous to that described for example 1 starting from 25 [2- (5-Amino-6-methoxy-pyridin-2-yloxy) -ethyl] -propyl- (acid) carbamic acid, tert ester -butyl and 4- (2,2,2-trifluoroethoxy) -benzenesulfonyl chloride.

MS (ESI) m / z: 464.05 [M + H] +

1H-NMR (D6-DMSO): δ [ppm] 9.45 (s, 1H), 9.15 (s br., 2H), 7.60 (d, 2H), 7.45 (d, 1H), 7.25 (d, 2H), 6.39 (d, 1H), 4.85-4.90 (m, 2H), 4.45-4.50 (m, 2H), 3.55 (s, 3H), 3.25 (s br., 2H), 2.88 (s br., 2H), 1.60-1.70 (m, 2H), 0.90 (t, 3H). 30

EXAMPLE 11

4- (R-2-Fluoro-1-methyl-ethyl) -N- [2-methoxy-6- (2-propylamino-ethoxy) -pyridin-3-yl] benzenesulfonamide x HCl

The desired product was obtained following the synthetic procedure analogous to that described for example 1 starting from [2- (5-Amino-6-methoxy-pyridin-2-yloxy) -ethyl] -propyl- (acid) carbamic acid, tert-ester butyl and 4 - ((R) -2-Fluoro-1-methyl-ethyl) -benzenesulfonyl chloride. 35

MS (ESI) m / z: 426.15 [M + H] +

1H-NMR (D6-DMSO): δ [ppm] 9.49 (s, 1H), 9.15 (s br., 2H), 7.60 (d, 2H), 7.50 (d, 1H), 7.45 (d, 2H), 6.40 (d, 1H), 4.45-4.60

(m, 4H), 3.45 (s, 3H), 3.20-3.30 (m, 3H), 2.90 (s br., 2H), 1.60-1.70 (m, 2H), 1.22 (d, 3H), 0.90 (t , 3H).

EXAMPLE 12 40

4 ((S) -2-Fluoro-1-methyl-ethyl-N- [2-methoxy-6- (2-propylamino-ethoxy) -pyridin-3-yl] benzenesylphonamine x HCl

To a solution of 6- [2- (benzyl-propyl-amino) -ethoxy] -2-methoxy-pyridin-3-ylamine (60 mg, 0.20 mmol) in pyridine (0.8 ml) was added 4- (SS) chloride ) -2-fluoro-1-methyl-ethyl) -benzenesulfonyl (50 mg / 0.20 mmol) at 0 ° C. The mixture was stirred at room temperature for 16 hours after which the solvent was evaporated under reduced pressure. The residue was purified by chromatography on silica gel with dichloromethane / ethyl acetate (10: 0; 9: 1; 0:10) /0.2% of 5 triethylamine as eluent. A mixture of the oil thus obtained was hydrogenated using the ThalesNano N-Cube® hydrogenation reactor using a 10% palladium catalyst cartridge in carbon. After filtration and evaporation of the solvent under reduced pressure the residue was purified by chromatography (Cromabond-C18) with H2O / acetonitrile (95: 5; 0: 100; 95: 5) /0.1% acetic acid as eluent. To a solution of the oil thus obtained in 2-propanol, HCl in diethyl ether was added. The solid formed was titrated and dried in a vacuum oven to give 10 mg 10 (20.3%) of the title compound.

MS (ESI) m / z: 426.15 [M + H] +

1H-NMR (D6-DMSO): δ [ppm] 9.49 (s, 1H), 9.15 (s br., 2H), 7.60 (d, 2H), 7.50 (d, 1H), 7.45 (d, 2H), 6.40 (d, 1H), 4.45-4.60 (m, 4H), 3.45 (s, 3H), 3.20-3.30 (m, 3H), 2.90 (s br., 2H), 1.60-1.70 (m, 2H), 1.22 (d, 3H), 0.90 (t , 3H).

EXAMPLE 13 15

4-Isipropyl-N- [2-methoxy-6- (pyrrolidin-3-yloxy) -pyridin-3-yl] -Benzenesulfonamide x HCl

After a solution of 6- (1-Benzyl-pyrrolidin-3-yloxy) -2-methoxy-pyridin-3-ylamine (120 mg, 0.40 mmol) in pyridine (2 ml) was stirred at room temperature for 30 minutes , 4-isopropyl benzenesulfonyl chloride (100 mg, 0.44 mmol) was added. The mixture was stirred at room temperature for 16 hours, after which the solvent was evaporated under reduced pressure. The residue was taken in toluene and the solvent was evaporated. This procedure was repeated once. The residue was purified by chromatography on silica gel with dichloromethane / ethyl acetate (10: 0; 9: 1; 0:10) /0.2% of triethanolamine as eluent. A mixture of the oil thus obtained and 10% palladium in carbon (20 mg, 0.02 mmol) in ethanol (20 ml) was hydrogenated at atmospheric pressure until hydrogen consumption was completed. After filtration and evaporation of the solvent under reduced pressure, the residue was purified by silica gel chromatography with dichloromethane / methanol (10: 0; 0:10; 10: 0) as eluent. To a solution of the oil thus obtained in methanol 25 was added HCl in diethyl ether, and the solution was concentrated under reduced pressure to obtain 31 mg (33.2%) of the title compound.

MS (ESI) m / z: 392.35 [M + H] +

1H-NMR (MeOD): δ [ppm] 7.65 (d, 1H), 7.60 (d, 2H), 7.35 (d, 2H), 6.35 (d, 1H), 5.55 (br., 1H), 3.45 -3.60 (m, 4H), 3.55

(s, 3H), 2.90-3.05 (m, 1H), 2.30-2.40 (m, 2H), 1.60-1.70 (m, 2H), 1.25 (d, 3H). 30

EXAMPLE 14

N- [2-Methoxy-6- (pyrrolidin-3-yloxy) -pyridin-3-yl] -4-trifluoromethoxy-benzenesulfonamide x HCl

The desired product was obtained following the synthetic procedure analogous to that described for example 13 starting from 6- (1-Benzyl-pyrrolidin-3-yloxy) -2-methoxy-pyridin-3-ylamine and 4-trifluoromethoxy-benzenesulfonyl chloride.

MS (ESI) m / z: 434.35 [M + H] + 35

1H-NMR (MeOD): δ [ppm] 7.92 (d, 1H), 7.80 (d, 2H), 7.405 (d, 2H), 6.40 (d, 1H), 5.57 (br., 1H), 3.45- 3.60 (m, 4H), 3.55 (s, 3H), 2.30-2.40 (m, 2H).

EXAMPLE 15

4- (3-Fluoro-propyl) -N- [2-methoxy-6- (2-pyrrolidin-1-yl-ethoxy) -pyridin-3-yl] -benzenesulfonamide

After a solution of 2-methoxy-6- (2-pyrrolidin-1-yl-ethoxy) -pyridin-3-ylamine (200 mg, 0.84 mmol) in pyridine (3 40 ml) was stirred at room temperature for 30 minutes 4- (3-fluoropropyl) benzenesulfonyl chloride (200 mg, 0.84 mmol) was added. The mixture was stirred at room temperature for 16 hours, after which the solvent was evaporated under reduced pressure. The residue was taken in toluene and the solvent was evaporated. This procedure was repeated once. The residue was purified by silica gel chromatography with dichloromethane / methanol (100: 0; 95: 5; 0: 100) as eluent to give 20 mg (5.4%) of the title compound 45

MS (ESI) m / z: 438.15 [M + H] +

1H-NMR (CDCl3): δ [ppm] 7.72 (d, 1H), 7.60 (d, 2H), 7.25 (d, 2H), 6.60 (s, 1H), 6.30 (d, 1H), 4.60-4.65 (m, 2H), 4.35-4.50

(m, 2H), 3.85-3.95 (m, 2H), 3.60 (s, 3H), 3.40-3.45 (m, 2H), 2.90-3.00 (m, 2H), 2.05-2.20 (m, 4H), 1.95 -2.05 (m, 2H).

EXAMPLE 16

4-Isopropyl-N- [2-methoxy-6- (2-pyrrolidin-1-yl-ethoxy) -pyridin-3-yl] -benzenesulfonamide x HCl

The desired product was obtained following the synthetic procedure analogous to that described for example 15 starting from 5-2-Methoxy-6- (2-pyrrolidin-1-yl-ethoxy) -pyridin-3-ylamine and 4-isopropyl-benzenesulfonyl chloride.

MS (ESI) m / z: 420.15 [M + H] +

EXAMPLE 17

4 - ((R) -2-Fluoro-1-methyl-ethyl) -N- [2-methoxy-6- (2-pyrrolidin-1-yl-ethoxy) -pyridin-3-yl] -benzenesulfonamide

The desired product was obtained following the synthetic procedure analogous to that described for example 15 starting from 10-2-Methoxy-6- (2-pyrrolidin-1-yl-ethoxy) -pyridin-3-ylamine and 4 - ((R) - 2-Fluoro-1-methyl-ethyl) -benzenesulfonyl chloride.

MS (ESI) m / z: 438.15 [M + H] +

1H-NMR (CDCl3): δ [ppm] 7.65 (d, 2H), 7.15-7.30 (m, 3H), 6.20-6.35 (d, 1H), 4.35-4.50 (m, 2H), 4.25-4.35 (m , 2H), 3.55 (s, 3H), 3.05-3.20 (m, 1H), 2.70-2.85 (m, 2H), 2.55-2.60 (m, 4H), 1.75-1.80 (m, 4H), 1.30 (d , 3H).

EXAMPLE 18 15

N- [2-Methoxy-6- (2-pyrrolidin-1-yl-ethoxy) -pyridin-3-yl] -4- (2,2,2-trifluoro-1-methylethyl) -benzenesulfonamide

The desired product was obtained following the synthetic procedure analogous to that described for example 15 starting from 2-Methoxy-6- (2-pyrrolidin-1-yl-ethoxy) -pyridin-3-ylamine and 4- (2,2,2 -trifluoro-1-methyl-ethyl) -benzenesulfonyl chloride.

MS (ESI) m / z: 474.25 [M + H] +

1H-NMR (CDCl3): δ [ppm] 7.70 (d, 1H), 7.65 (d, 2H), 7.35 (d, 2H), 6.35 (d, 1H), 4.35-4.40 (m, 2H), 3.50 ( s, 3H), 2.85-20 2.92 (m, 2H), 2.60-2.73 (m, 4H), 1.80-1.90 (m, 4H), 1.50 (d, 3H).

EXAMPLE 19

N- [2-Methoxy-6- (2-pyrrolidin-1-yl-ethoxy) -pyridin-3-yl] -4-oxazol-5-ylbenzenesulfonamide

The desired product was obtained following the synthetic procedure analogous to that described for example 15 starting from 2-Methoxy-6- (2-pyrrolidin-1-yl-ethoxy) -pyridin-3-ylamine and 4-oxazol-5-yl- benzenesulfonyl chloride. 25

MS (ESI) m / z: 445.15 [M + H] +

1H-NMR (MeOD): δ [ppm] 8.35 (s, 1H), 7.85 (d, 2H), 7.75 (d, 2H), 7.71 (d, 1H), 7.69 (s, 1H), 6.45 (d, 1H), 4.55-4.60 (m, 2H), 3.65-3.75 (m, 2H), 3.60 (s, 3H), 3.60-3.65 (m, 2H), 3.15-3.25 (m, 2H), 2.00-2.25 ( m, 4H).

EXAMPLE 20

4-Isopropyl-N- [4-methoxy-2- (2-propylamino-ethoxy) -pyrimidin-5-yl] -benzenesulfonamide 30

The desired product was obtained following the synthetic procedure analogous to that described for example 1 starting from [2- (5-Amino-4-methoxy-pyrimidin-2-yloxy) -ethyl] -propyl- (acid) carbamic acid, tert-ester butyl and 4-isopropylbenzenesulfonyl chloride.

MS (ESI) m / z: 409.15 [M + H] +

1H-NMR (DMSO): δ [ppm] 8.00 (s, 1H), 7.55 (d, 2H), 7.48 (d, 2H), 4.25-4.30 (m, 2H), 3.50 (s, 3H), 2.90- 3.00 (m, 1H), 35 2.85-2.92 (m, 2H), 2.55-2.60 (m, 2H), 1.37-1.50 (m, 2H), 1.20 (d, 6H), 0.85 (t, 3H).

EXAMPLE 21

N- [4-Methoxy-2- (2-propylamino-ethoxy) -pyrimidin-5-yl] -4-trifluoromethoxy-benzenesulfonamide

The desired product was obtained following the synthetic procedure analogous to that described for example 1 starting from [2- (5-Amino-4-methoxy-pyrimidin-2-yloxy) -ethyl] -propyl- (acid) carbamic acid, tert-ester butyl and 4-trifluoromethoxybenzenesulfonyl chloride. -

MS (ESI) m / z: 451.15 [M + H] + 5

1H-NMR (MeOD): δ [ppm] 8.02 (s, 1H), 7.74 (d, 2H), 7.28 (d, 2H), 4.30-4.35 (m, 2H), 3.55 (s, 3H), 2.95- 3.00 (m, 2H), 2.60-2.67 (m, 2H), 1.48-1.52 (m, 2H), 0.87 (t, 3H).

EXAMPLE 22

N- [6- (2-Dimethylamino-ethoxy) -pyridin-3-yl] -4-isopropyl-benzenesulfonamide x HCl

The desired product was obtained following the synthetic procedure analogous to that described for example 15 starting from 10 of 6- (2-Dimethylamino-ethoxy) -pyridin-3-ylamine and 4-isopropyl-benzenesulfonyl chloride.

MS (ESI) m / z: 364.15 [M + H] +

EXAMPLE 23

4-Isopropyl-N- [6- (2-propylamino-ethoxy) -pyridin-3-yl] -benzenesulfonamide x HCl

The desired product was obtained following the synthetic procedure analogous to that described for example 1 starting from 15 [2- (5-Amino-pyridin-2-yloxy) -ethyl] -propyl- (acid) carbamic, tert-butyl ester and 4 -isopropyl benzenesulfonyl chloride.

MS (ESI) m / z: 378.15 [M + H] +

EXAMPLE 24

N- [6- (2-Dipropylamino-ethoxy) -pyridin-3-yl] -4-isopropyl-benzenesulfonamide x HCl

To a solution of 4-Isopropyl-N- [6- (2-propylamino-ethoxy) -pyridin-3-yl] -benzenesylphonamide (81 mg, 0.21 mmol), propionaldehyde (13.71 mg, 0.24 mmol) and acetic acid ( 0.02 ml) in dichloromethane (5 ml), sodium trisacetoxy borohydride (68.22 mg, 0.32 mmol) was added. The mixture was stirred at room temperature for 1 hour. After evaporation of the solvent under reduced pressure, the residue was dissolved in 1N NaOH, which was extracted 3 times with diethyl ether. The combined organic layers were dried over MgSO4, filtered and the solvent was evaporated under reduced pressure. To a solution of the residue in diethyl ether at 0 ° C was added HCl in diethyl ether. The solid formed was filtered 25 and dried in a vacuum oven to give 66 mg (67.4% of the title compound).

MS (ESI) m / z: 420.25 [M + H] +

1H-NMR (DMSO): δ  [ppm] 10.20 (br., 2H), 7.85 (s, 1H), 7.65 (d, 2H), 7.50 (d, 1H), 7.45 (d, 2H), 6.80 (d, 1H), 4.50-4.57 (m, 2H), 3.40-3.50 (m, 2H), 3.00-3.10 (m, 4H), 2.90-3.00 (m, 1H), 1.60-1.70 (m, 4H) , 1.20 (d, 6H), 0.90 (t, 6H).

The following examples were obtained according to the synthetic procedure analogous to that described for example 30 1.

EXAMPLE 25

4-Isopropyl-N- [2-methoxy-6 - ((R) -1-pyrrolidin-2-ylmethoxy) -pyridin-3-yl] -benzenesulfonamide x HCl

MS (ESI) m / z: 392.1 [M + H] +

1H-NMR (DMSO): δ [ppm] 9.20-9.70 (m, 2H), 7.60 (d, 2H), 7.50 (d, 1H), 7.40 (d, 2H), 6.40 (d, 1H), 4.38- 4.48 (m, 2H), 35 3.85-88 (m, 1H), 3.52 (s, 3H), 3.12-3.22 (m, 2H), 2.97-2.99 (m, 1H), 2.05-2.15 (m, 1H) , 1.85-2.05 (m, 2H), 1.68-1.70 (m, 1H), 1.23 (d, 6H).

EXAMPLE 26

4- (2-Fluoro-ethoxy) -N- [2-methoxy-6 - ((R) -1-pyrrolidin-2-ylmethoxy) -pyridin-3-yl] -benzenesulfonamide x HCl

MS (ESI) m / z: 426.1 [M + H] + 40

1H-NMR (DMSO): δ [ppm] 9.98 (bs, 1H), 9.32-9.38 (m, 2H), 7.58 (d, 2H), 7.38 (d, 1H), 7.09 (d, 2H), 6.36 ( d, 1H), 4.68-4.80 (m, 2H), 4.36-4.45 (m, 2H), 4.27-4.35 (m, 2H), 3.80-3.86 (m, 1H), 3.55 (s, 3H), 3.12- 3.20 (m, 2H), 2.03-2.10 (m, 1H), 1.83-1.97 (m, 2H), 1.64-1.72 (m, 1H).

EXAMPLE 27

N- [2-Methoxy-6 - ((R) -1-pyrrolidin-2-ylmethoxy) -pyridin-3-yl] -4-oxazol-5-ylbenzenesulfonamide x HCl 5

MS (ESI) m / z: 431.1 [M + H] +

1H-NMR (DMSO): δ [ppm] 9.82-9.92 (m, 1H), 9.63 (s, 1H), 9.22-9.28 (m, 1H), 8.53 (s, 1H), 7.88 (d, 2H), 7.87 (s, 1H), 7.48 (d, 1H), 6.38 (d, 1H), 4.32-4.46 (m, 2H), 3.80-88 (m, 1H), 3.49 (s, 3H), 3.12-3.22 ( m, 2H), 2.02-2.10 (m, 1H), 1.82-1.98 (m, 2H), 1.62-1.72 (m, 1H).

EXAMPLE 28 10

4-Isopropyl-N- [2-methoxy-6 - ((S) -1-pyrrolidin-2-ylmethoxy) -pyridin-3-yl] -benzenesulfonamide x HCl

MS (ESI) m / z: 392.1 [M + H] +

1H-NMR (DMSO): δ [ppm] 9.20-9.70 (m, 2H), 7.60 (d, 2H), 7.50 (d, 1H), 7.40 (d, 2H), 6.40 (d, 1H), 4.38- 4.48 (m, 2H), 3.85-88 (m, 1H), 3.52 (s, 3H), 3.12-3.22 (m, 2H), 2.97-2.99 (m, 1H), 2.05-2.15 (m, 1H), 1.85-2.05 (m, 2H), 1.68-1.70 (m, 1H), 1.23 (d, 6H). fifteen

EXAMPLE 29

4-Isopropyl-N- [2-methyl-6- (2-propylamino-ethoxy) -pyridin-3-yl] -benzenesulfonamide x HCl

MS (ESI) m / z: 392.1 [M + H] +

1H-NMR (MeOD): δ [ppm] 7.63 (d, 2H), 7.47 (d, 1H), 7.43 (d, 2H), 6.78 (d, 1H), 4.58-4.62 (m, 2H), 3.45- 3.51 (m, 2H), 3.00-3.10 (m, 3H), 2.14 (s, 3H), 1.72-1.85 (m, 2H), 1.30 (d, 6H), 1.07 (t, 3H). twenty

EXAMPLE 30

N- [2-Methyl-6- (2-propylamino-ethoxy) -pyridin-3-yl] -4-trifluoromethoxy-benzenesulfonamide x HCl

MS (ESI) m / z: 434.1 [M + H] +

1H-NMR (MeOD): δ [ppm] 7.81 (d, 2H), 7.46 (d, 2H), 7.40 (d, 1H), 6.72 (d, 1H), 4.57-4.59 (m, 2H), 3.44- 3.46 (m, 2H), 3.05-3.08 (m, 2H), 2.14 (s, 3H), 1.72-1.81 (m, 2H), 1.05 (t, 3H). 25

EXAMPLE 31

4-Difluoromethoxy-N- [2-methyl-6- (2-propylamino-ethoxy) -pyridin-3-yl] -benzenesulfonamide x HCl

MS (ESI) m / z: 416.1 [M + H] +

1H-NMR (DMSO): δ [ppm] 9.85 (s, 1H), 9.33 (bs, 2H), 7.71 (d, 2H), 7.42 (t, 1H), 7.36 (d, 2H), 7.22 (d, 1H), 6.63 (d, 1H), 4.47-4.49 (m, 2H), 3.24-3.27 (m, 2H), 2.85-2.91 (m, 2H), 2.10 (s, 3H), 1.63-1.72 (m, 2H), 0.90 (t, 3H). 30

EXAMPLE 32

4- (2,2-Difluoro-ethoxy) -N- [2-methyl-6- (2-propylamino-ethoxy) -pyridin-3-yl] -benzenesulfonamide x HCl

MS (ESI) m / z: 430.1 [M + H] +

1H-NMR (DMSO): δ [ppm] 9.66 (s, 1H), 9.34 (bs, 2H), 7.61 (d, 2H), 7.23 (d, 1H), 7.18 (d, 2H), 6.63 (d, 1H), 6.31-6.55 (m, 1H), 4.40-4.50 (m, 4H), 3.24-3.30 (m, 2H), 2.85-2.95 (m, 2H), 2.11 (s, 3H), 1.65-1.75 ( m, 2H), 0.90 (t, 3H). 35

EXAMPLE 33

4- (2-Fluoro-ethoxy) -N- [2-methyl-6- (2-propylamino-ethoxy) -pyridin-3-yl] -benzenesulfonamide x HCl

MS (ESI) m / z: 412.1 [M + H] +

1H-NMR (DMSO): δ [ppm] 9.62 (s, 1H), 9.32 (bs, 2H), 7.60 (d, 2H), 7.23 (d, 1H), 7.13 (d, 2H), 6.64 (d, 1H), 4.70-4.85 (m, 2H), 4.48-4.50 (m, 2H), 4.30-4.39 (m, 2H), 3.24-3.32 (m, 2H), 2.85-2.95 (m, 2H), 2.11 ( s, 3H), 1.65-1.75 (m, 2H), 0.90 (t, 3H).

EXAMPLE 34 5

4 - ((R) -2-Fluoro-1-methyl-ethyl) -N- [2-methyl-6- (2-propylamino-ethoxy) -pyridin-3-yl] -benzenesulfonamide x HCl

MS (ESI) m / z: 410.1 [M + H] +

1H-NMR (DMSO): δ [ppm] 9.74 (s, 1H), 9.35 (bs, 2H), 7.61 (d, 2H), 7.50 (d, 2H), 7.26 (d, 1H), 6.63 (d, 1H), 4.40-4.62 (m, 4H), 3.20-3.30 (m, 2H), 3.05-3.08 (m, 1H), 2.85-2.95 (m, 2H), 2.04 (s, 3H), 1.65-1.75 ( m, 2H), 1.24 (d, 3H), 0.91 (t, 3H).

EXAMPLE 35 10

4 - ((S) -2-Fluoro-1-methyl-ethyl) -N- [2-methyl-6- (2-propylamino-ethoxy) -pyridin-3-yl] -benzenesulfonamide x HCl

MS (ESI) m / z: 410.1 [M + H] +

1H-NMR (DMSO): δ [ppm] 9.77 (s, 1H), 9.38 (bs, 2H), 7.61 (d, 2H), 7.50 (d, 2H), 7.26 (d, 1H), 6.63 (d, 1H), 4.40-4.62 (m, 4H), 3.20-3.30 (m, 3H), 2.85-2.95 (m, 2H), 2.04 (s, 3H), 1.65-1.75 (m, 2H), 1.24 (d, 3H), 0.89 (t, 3H)

EXAMPLE 36 15

N- [2-Methyl-6- (2-propylamino-ethoxy) -pyridin-3-yl] -4-oxazol-5-ylbenzenesulfonamide x HCl

MS (ESI) m / z: 417.1 [M + H] +

1H-NMR (DMSO): δ [ppm] 9.92 (s, 1H), 9.35 (bs, 2H), 8.57 (s, 1H), 7.93 (d, 2H), 7.92 (s, 1H), 7.45 (d, 2H), 7.24 (d, 1H), 6.64 (d, 1H), 4.47-4.50 (m, 2H), 3.24-3.30 (m, 2H), 2.85-2.92 (m, 2H), 2.11 (s, 3H) , 1.64-1.73 (m, 2H), 0.90 (t, 3H).

EXAMPLE 37 20

N- [2-Methyl-6- (2-propylamino-ethoxy) -pyridin-3-yl] -4-oxazol-4-ylbenzenesulfonamide x HCl

MS (ESI) m / z: 417.1 [M + H] +

1H-NMR (DMSO): δ [ppm] 9.86 (s, 1H), 9.31 (bs, 2H), 8.84 (s, 1H), 8.54 (s, 1H), 7.99 (d, 2H), 7.72 (d, 2H), 7.25 (d, 1H), 6.65 (d, 1H), 4.47-4.50 (m, 2H), 3.20-3.30 (m, 2H), 2.85-2.92 (m, 2H), 2.11 (s, 3H) , 1.64-1.72 (m, 2H), 0.90 (t, 3H).

EXAMPLE 38 25

N- [2-Methyl-6 - ((S) -1-pyrrolidin-2-ylmethoxy) -pyridin-3-yl] -4-oxazol-5-ylbenzenesulfonamide x HCl

MS (ESI) m / z: 379.1 [M + H] +

1H-NMR (DMSO): δ [ppm] 9.60-9.80 (m, 2H), 9.00-9.10 (m, 1H), 8.52 (bs, 1H), 7.85-7.90 (m, 3H), 7.69 (d, 2H ), 7.21 (d, 1H), 6.60 (d, 1H), 4.28-4.41 (m, 2H), 3.80-3.90 (m, 1H), 3.10-3.20 (m, 2H), 2.05-2.10 (m, 4H ), 1.80-1.95 (m, 2H), 1.65-1.75 (m, 1H). 30

EXAMPLE 39

4- (2,2-Difluoro-ethoxy) -N- [2-methyl-6 - ((S) -1-pyrrolidin-2-ylmethoxy) -pyridin-3-yl] -benzenesulfonamide x HCl

MS (ESI) m / z: 428.1 [M + H] +

1H-NMR (DMSO): δ [ppm] 9.50-9.60 (m, 2H), 8.90-9.00 (m, 1H), 7.89 (d, 2H), 7.24 (d, 1H), 7.18 (d, 2H), 6.64 (d, 1H), 6.28-6.57 (m, 1H), 4.28-4.48 (m, 4H), 3.80-3.90 (m, 1H), 3.15-3.25 (m, 2H), 2.05-2.15 (m, 4H ), 1.85-2.00 (m, 2H), 1.70-35 1.80 (m, 1H).

EXAMPLE 40

4- (2-Fluoro-ethoxy) -N- [2-methyl-6 - ((S) -1-pyrrolidin-2-ylmethoxy) -pyridin-3yl] -benzenesulfonamide x HCl

MS (ESI) m / z: 410.1 [M + H] +

1H-NMR (DMSO): δ [ppm] 9.60-9.70 (m, 1H), 9.54 (s, 1H), 8.95-9.05 (m, 1H), 7.58 (d, 2H), 7.24 (d, 1H), 7.13 (d, 2H), 6.64 (d, 1H), 4.71-4.85 (m, 2H), 4.30-4.50 (m, 4H), 3.80-3.90 (m, 1H), 3.15-3.25 (m, 2H), 2.05-2.15 (m, 4H), 1.85-2.00 (m, 2H), 1.70-1.80 (m, 1H). 5

EXAMPLE 41

N- [2-Methyl-6 - ((S) -1-pyrrolidin-2-ylmethoxy) -pyridin-3-yl] -4-trifluoromethoxybenzenesulfonamide x HCl

MS (ESI) m / z: 432.1 [M + H] +

1H-NMR (DMSO): δ [ppm] 9.90 (s, 1H), 9.60-9.70 (m, 1H), 8.95-9.05 (m, 1H), 7.79 (d, 2H), 7.60 (d, 2H), 7.27 (d, 1H), 6.66 (d, 1H), 4.31-4.47 (m, 2H), 3.85-3.95 (m, 1H), 3.15-3.25 (m, 2H), 2.05-2.15 (m, 4H), 1.85-2.00 (m, 2H), 1.70-1.80 10 (m, 1H).

EXAMPLE 42

4 - ((R) -2-Fluoro-1-methyl-ethyl) -N- [2-methyl-6 - ((S) -1-pyrrolidin-2-ylmethoxy) -pyridin-3-yl] -benzenesulfonamide x HCl

MS (ESI) m / z: 408.1 [M + H] +

1H-NMR (DMSO): δ [ppm] 9.65 (s, 1H), 9.45-9.55 (m, 1H), 8.85-8.95 (m, 1H), 7.60 (d, 2H), 7.51 (d, 2H), 7.28 (d, 1H), 15 6.65 (d, 1H), 4.48-4.62 (m, 2H), 4.30-4.47 (m, 2H), 3.85-3.95 (m, 1H), 3.20-3.30 (m, 2H) , 2.08-2.15 (m, 1H), 2.04 (s, 3H), 1.85-2.00 (m, 2H), 1.70-1.80 (m, 1H), 1.27 (d, 3H).

EXAMPLE 43

4-Isopropyl-N- [2-methyl-6 - ((S) -1-pyrrolidin-2-ylmethoxy) -pyridin-3-yl] -benzenesulfonamide x HCl

MS (ESI) m / z: 390.1 [M + H] + 20

1H-NMR (DMSO): δ [ppm] 9.55-9.65 (m, 2H), 8.93-9.02 (m, 1H), 7.57 (d, 2H), 7.45 (d, 2H), 7.28 (d, 1H), 6.65 (d, 1H), 4.30-4.45 (m, 4H), 3.85-3.95 (m, 1H), 3.15-3.25 (m, 2H), 2.95-3.05 (m, 1H), 2.08-2.15 (m, 1H ), 2.04 (s, 3H), 1.85-2.00 (m, 2H), 1.70-1.80 (m, 1H), 1.24 (d, 3H).

EXAMPLE 44

N- [2-Methyl-6 - ((R) -1-pyrrolidin-2-ylmethoxy) -pyridin-3-yl] -4-oxazol-5-ylbenzenesulfonamide x HCl 25

MS (ESI) m / z: 379.1 [M + H] +

1H-NMR (DMSO): δ [ppm] 9.75 (s, 1H), 9.14-9.24 (m, 1H), 8.64-8.74 (m, 1H), 8.57 (s, 1H), 7.90-7.95 (m, 3H ), 7.73 (d, 2H), 7.27 (d, 1H), 6.65 (d, 1H), 4.26-4.47 (m, 2H), 3.85-3.94 (m, 1H), 3.20-3.25 (m, 2H), 2.07-2.15 (m, 4H), 1.90-2.10 (m, 2H), 1.70-1.80 (m, 1H).

EXAMPLE 45 30

4-Isopropyl-N- [2-methyl-6 - ((R) -1-pyrrolidin-2-ylmethoxy) -pyridin-3-yl] -benzenesulfonamide x HCl

MS (ESI) m / z: 354.1 [M + H] +

1H-NMR (DMSO): δ [ppm] 9.59 (s, 1H), 9.36-9.44 (m, 1H), 8.78-8.86 (m, 1H), 7.57 (d, 2H), 7.45 (d, 2H), 7.28 (d, 1H), 6.65 (d, 1H), 4.28-4.47 (m, 4H), 3.85-3.94 (m, 1H), 3.18-3.25 (m, 2H), 2.95-3.05 (m, 1H), 2.08-2.15 (m, 1H), 2.04 (s, 3H), 1.88-2.00 (m, 2H), 1.70-1.80 (m, 1H), 1.24 (d, 3H). 35

The following examples were obtained according to the systhetic procedure analogous to that described for example 12.

EXAMPLE 46

4 - ((R) -2,2-Difluoro-1-methyl-ethyl) -N- [2-methoxy-6- (2-propylamino-ethoxy) -pyridin-3-yl] -benzenesulfonamide x HCl

MS (ESI) m / z: 444.1 [M + H] +

1H-NMR (DMSO): δ [ppm] 9.54 (s, 1H), 9.44 (bs, 2H), 7.61-7.63 (m, 2H), 7.49-7.52 (m, 3H), 6.40 (d, 1H), 6.10-6.34 (m, 1H), 4.50-4.52 (m, 2H), 3.43 (s, 3H), 3.32-3.40 (m, 1H), 3.25-3.28 (m, 2H), 2.85-2.90 (m, 2H ), 1.65-1.73 (m, 2H), 1.31 (d, 3H), 0.89 (t, 3H).

EXAMPLE 47 5

4 - ((S) -2,2-Difluoro-1-methyl-ethyl) -N- [2-methoxy-6- (2-propylamino-ethoxy) -pyridin-3-yl] -benzenesulfonamide x HCl

MS (ESI) m / z: 444.1 [M + H] +

1H-NMR (DMSO): δ [ppm] 9.54 (s, 1H), 9.44 (bs, 2H), 7.61-7.63 (m, 2H), 7.49-7.52 (m, 3H), 6.40 (d, 1H), 6.10-6.34 (m, 1H), 4.50-4.52 (m, 2H), 3.43 (s, 3H), 3.32-3.40 (m, 1H), 3.25-3.28 (m, 2H), 2.85-2.90 (m, 2H ), 1.65-1.73 (m, 2H), 1.31 (d, 3H), 0.89 (t, 3H). 10

EXAMPLE 48

N- [2-Methoxy-6- (2-propylamino-ethoxy) -pyridin-3-yl] -4-oxazol-4-ylbenzenesulfonamide x HCl

MS (ESI) m / z: 433.1 [M + H] +

1H-NMR (DMSO): δ [ppm] 9.58 (s, 1H), 9.25 (bs, 2H), 8.81 (s, 1H), 8.54 (s, 1H), 7.96 (d, 2H), 7.71 (d, 2H), 7.49 (d, 1H), 6.40 (d, 1H), 6.10-6.34 (m, 1H), 4.48-4.51 (m, 2H), 3.52 (s, 3H), 3.25-3.28 (m, 2H) , 2.85-2.90 (m, 2H), 1.63-1.71 (m, 2H), 15 0.90 (t, 3H).

EXAMPLE 49

N- [2-Methoxy-6- (2-propylamino-ethoxy) -pyridin-3-yl] -4-pyrazol-1-ylbenzenesulfonamide x HCl

MS (ESI) m / z: 432.1 [M + H] +

1H-NMR (DMSO): δ [ppm] 9.59 (s, 1H), 8.94 (bs, 2H), 8.61 (d, 1H), 8.01 (d, 2H), 7.82 (s, 1H), 7.75 (d, 2H), 7.50 (d, 1H), 20 6.61 (bs, 1H), 6.40 (d, 1H), 4.42-4.47 (m, 2H), 3.54 (s, 3H), 3.25-3.30 (m, 2H), 2.85-2.95 (m, 2H), 1.56-1.68 (m, 2H), 0.89 (t, 3H).

EXAMPLE 50

4- (3-Fluoro-propyl) -N- [2-methyl-6- (2-propylamino-ethoxy) -pyridin-3-yl] -benzenesulfonamide x HCl

MS (ESI) m / z: 410.1 [M + H] + 25

1H-NMR (DMSO): δ [ppm] 9.72 (s, 1H), 9.36 (bs, 2H), 7.56 (d, 2H), 7.41 (d, 2H), 7.22 (d, 1H), 6.61 (d, 1H), 4.35-4.48 (m, 4H), 3.20-3.30 (m, 2H), 2.83-2.90 (m, 2H), 2.70-2.76 (m, 2H), 2.03 (s, 3H), 1.85-2.00 ( m, 2 H), 1.62-1.71 (m, 2H), 0.89 (t, 3H).

EXAMPLE 51

N- [2-Methyl-6- (2-propylamino-ethoxy) -pyridin-3-yl] -4 - ((R) -2,2,2-trifluoro-1-methylethyl) -benzenesulfonamide x HCl 30

MS (ESI) m / z: 446.1 [M + H] +

1H-NMR (DMSO): δ [ppm] 9.86 (s, 1H), 9.36 (bs, 2H), 7.66 (d, 2H), 7.60 (d, 2H), 7.25 (d, 1H), 6.62 (d, 1H), 4.45-4.48 (m, 2H), 3.90-4.02 (m, 1H), 3.20-3.30 (m, 2H), 2.83-2.90 (m, 2H), 1.98 (s, 3H), 1.62-1.71 ( m, 2H), 1.44 (d, 3H), 0.89 (t, 3H).

EXAMPLE 52

4 - ((R) -2,2-Difluoro-1-methyl-ethyl) -N- [2-methyl-6- (2-propylamino-ethoxy) -pyridin-3-yl] -benzenesulfonamide x HCl 35

MS (ESI) m / z: 428.1 [M + H] +

1H-NMR (DMSO): δ [ppm] 9.81 (s, 1H), 9.36 (bs, 2H), 7.62 (d, 2H), 7.52 (d, 2H), 7.24 (d, 1H), 6.62 (d, 1H), 6.09-6.32 (m, 1H), 4.45-4.48 (m, 2H), 3.34-3.42 (m, 1H), 3.22-3.27 (m, 2H), 2.83-2.90 (m, 2H), 2.01 ( s, 3H), 1.62-1.71 (m, 2H), 1.30 (d, 3H), 0.89 (t, 3H).

EXAMPLE 53

N- [2-Methyl-6- (2-propylamino-ethoxy) -pyridin-3-yl] -4- (2,2,2-trifluoro-ethoxy) -benzenesulfonamide x HCl

MS (ESI) m / z: 412.1 [M + H] +

1H-NMR (DMSO): δ [ppm] 9.68 (s, 1H), 9.31 (bs, 2H), 7.62 (d, 2H), 7.22-7.24 (m, 3H), 6.63 (d, 1H), 4.87- 4.92 (m, 2H), 4.46-4.51 (m, 2H), 3.24-3.30 (m, 2H), 2.85-2.95 (m, 2H), 2.11 (s, 3H), 1.65-1.74 (m, 2H), 0.92 (t, 3H). 5

EXAMPLE 54

4 - ((R) -2,2-Difluoro-1-methyl-ethyl) -N- [4-methyl-6- (2-propylamino-ethoxy) -pyridin-3-yl] -benzenesulfonamide x HCl

MS (ESI) m / z: 428.1 [M + H] +

1H-NMR (DMSO): δ [ppm] 9.70 (s, 1H), 8.60-8.66 (m, 2H), 7.64-7.69 (m, 3H), 7.56 (d, 2H), 6.70 (s, 1H), 6.09-6.39 (m, 1H), 4.45-4.48 (m, 2H), 3.30-3.45 (m, 3H), 2.90-3.00 (m, 2H), 1.94 (s, 3H), 1.60-1.70 (m, 2H ), 1.35 (d, 3H), 0.94 (t, 3H). 10

EXAMPLE 55

N- [4-Methyl-6- (2-propylamino-ethoxy) -pyridin-3-yl] -4-oxazol-4-ylbenzenesulfonamide x HCl

MS (ESI) m / z: 381.1 [M + H] +

1H-NMR (DMSO): δ [ppm] 9.73 (s, 1H), 8.83 (s, 1H), 8.56-8.65 (m, 2H), 8.01 (d, 2H), 7.73 (d, 2H), 7.66 ( s, 1H), 6.71 (s, 1H), 4.44-4.47 (m, 2H), 3.30-3.45 (m, 2H), 2.90-3.00 (m, 2H), 2.01 (s, 3H), 1.60-1.68 ( m, 2H), 0.93 (t, 3H). fifteen

EXAMPLE 56

4- (2,2-Difluoro-ethoxy) -N- [4-methyl-6- (2-propylamino-ethoxy) -pyridin-3-yl] -benzenesulfonamide x HCl

MS (ESI) m / z: 394.1 [M + H] +

1H-NMR (DMSO): δ [ppm] 9.70 (s, 1H), 9.35 (bs, 2H), 7.58-7.62 (m, 3H), 7.17 (d, 1H), 6.69 (s, 1H), 6.29- 6.55 (m, 1H), 4.38-4.50 (m, 4H), 3.21-3.28 (m, 2H), 2.82-2.90 (m, 2H), 1.99 (s, 3H), 1.62-1.71 (m, 2H), 0.89 (t, 3H). twenty

EXAMPLE 57

4 - ((R) -2-Fluoro-1-methyl-ethyl) -N- [4-methyl-6- (2-propylamino-ethoxy) -pyridin-3-yl] -benzenesulfonamide x HCl

MS (ESI) m / z: 410.1 [M + H] +

1H-NMR (DMSO): δ [ppm] 9.76 (s, 1H), 9.32 (bs, 2H), 7.60-7.62 (m, 3H), 7.50 (d, 2H), 6.68 (s, 1H), 4.45- 4.59 (m, 4H), 3.20-3.30 (m, 3H), 2.84-2.91 (m, 2H), 1.92 (s, 3H), 1.63-1.71 (m, 2H), 1.23 (d, 3H), 0.89 ( t, 3H). 25

EXAMPLE 58

N- [4-Methyl-6- (2-propylamino-ethoxy) -pyridin-3-yl] -4-trifluoromethoxy-benzenesulfonamide x HCl

MS (ESI) m / z: 434.1 [M + H] +

1H-NMR (DMSO): δ [ppm] 9.88 (s, 1H), 8.80-8.90 (m, 1H), 7.79 (d, 2H), 7.58-7.63 (m, 3H), 6.70 (s, 1H), 4.43-4.46 (m, 2H), 3.44-3.46 (m, 2H), 3.25-3.35 (m, 2H), 2.85-2.95 (m, 2H), 1.95 (s, 3H), 1.58-1.68 (m, 2H ), 0.91 (t, 3H). 30

EXAMPLE 59

4-Isopropyl-N- [4-methyl-6- (2-propylamino-ethoxy) -pyridin-3-yl] -benzenesulfonamide x HCl

MS (ESI) m / z: 392.1 [M + H] +

1H-NMR (MeOD): δ [ppm] 7.73 (s, 1H), 7.63 (d, 2H), 7.42 (d, 2H), 6.81 (s, 1H), 4.55-4.58 (m, 2H), 3.44- 3.46 (m, 2H), 3.00-3.10 (m, 3H), 2.05 (s, 3H), 1.72-1.80 (m, 2H), 1.29 (d, 6H), 1.05 (t, 3H). 35

EXAMPLE 60

4- (2-Fluoro-ethoxy) -N- [5-methyl-6- (2-propylamino-ethoxy) -pyridin-3-yl] -benzenesulfonamide x HCl

MS (ESI) m / z: 376.1 [M + H] +

1H-NMR (DMSO): δ [ppm] 10.10 (s, 1H), 9.30 (bs, 2H), 7.62-7.66 (m, 3H), 7.31 (d, 1H), 7.09 (d, 2H), 4.70- 4.80 (m, 2H), 4.48-4.50 (m, 2H), 4.30-4.39 (m, 2H), 3.24-3.30 (m, 2H), 2.85-2.90 (m, 2H), 2.12 (s, 3H), 1.62-1.72 (m, 2H), 0.90 (t, 3H). 5

EXAMPLE 61

4-Isopropyl- N- {2-methyl-6 - [(1-propylpyrrolidin-3-yl) oxy] pyridin-3-yl} benzenesulfonamide (2 E) -but-2-enedioate

61.1 2-Methyl-3-nitro-6- (pyrrolidin-3-yloxy) pyridine

6-Methyl-5-nitropyridin-2-ol (5 g) was dissolved in tetrahydrofuran and DL-3-pyrrolidinol (2.83 g) and triphenylphosphine (12.76 g) was added. Di-tert-butyl (C) -diazeno-1,2-dicarboxylate (11.21 g) dissolved in tetrahydrofuran (15 ml) was added over 15 minutes 10 dropwise. The reaction mixture was stirred at room temperature for 50 hours. The reaction mixture was concentrated in vacuo. The remaining residue was suspended in dichloromethane and trifluoroacetic acid (7.55 mL) was added dropwise. The reaction mixture was stirred for 12 hours at room temperature. The reaction mixture was concentrated in vacuo, redissolved in dichloromethane and extracted several times with 1N hydrochloric acid. The combined aqueous extracts were treated with 1N NaOH at pH 10 and extracted with ethyl acetate (3x). The combined ethyl acetate extracts were washed successively with water and brine and dried (sodium sulfate). After concentration in vacuo, the crude product was purified by flash chromatography (silica, dichloromethane, 1-10% methanol gradient). Yield: 1.5 g (18.6%, pale yellow oil).

61.2 2-Methyl-3-nitro-6 - [(1-propionylpyrrolidin-3-yl) oxy] pyridine

2-Methyl-3-nitro-6- (pyrrolidin-3-yloxy) pyridine (1.3g) was dissolved in dichloromethane (20 ml) and triethylamine (1.57 ml) was added. The solution was cooled to 0 ° C and a solution of propionyl chloride (574 mg) in dichloromethane (5 ml) was added dropwise over 5 minutes. The reaction mixture was allowed to reach room temperature and was stirred for another 5 minutes. Water (10 ml) was added. After stirring for 3 minutes, the phases were separated and the aqueous layer was extracted with dichloromethane. The combined organic layers were dried (sodium sulfate) and concentrated in vacuo. The crude product was purified by flash chromatography (silica, dichloromethane / methanol = 98/2). 25 Yield 950 mg (64.9%, pale yellow oil).

61.3 2-Methyl-6 - [(1-propionylpyrrolidin-3-yl) oxy] pyridin-3-amine

2-Methyl-3-nitro-6 - [(1-propionylpyrrolidin-3-yl) oxy] pyridine (940 mg) was dissolved in methanol (50 mL), and hydrogenated (ThalesNano H-cube, 10% Pd / C, 60 ° C, 50 bar, 1 mL / minute). Methanol was removed in vacuo. Yield: 800 mg (95%, colorless oil). 30

61.44-Isopropyl-N- {2-methyl-6 - [(1-propionylpyrrolidin-3-yl) oxy] pyridin-3-yl} -benzenesulfonamide

2-Methyl-6 - [(1-propionyl-pyrrolidin-3-yl) -oxy] pyridine-3-amine (340 mg) was dissolved in pyridine (3.3 mL) and 4-isopropylbenzenesulfonyl chloride (358 mg) was added Slowly under agitation. After stirring for 19 hours at room temperature, the reaction mixture was diluted with dichloromethane and 2M aqueous NaOH solution was added. After stirring for 1 hour at room temperature the phases were separated. The organic phase was dried (sodium sulfate), concentrated and the crude product was purified by flash chromatography (silica, dichloromethane, 0.5 to 5% methanol gradient). Yield: 460 mg (78%, pale yellow oil).

61.5 4-Isopropyl-N- {2-methyl-6 - [(1-propylpyrrolidin-3-yl) oxy] pyridin-3-yl} -benzenesulfonamide (2E) -but-2-enedioate

Lithium aluminum hydride (88 mg) was suspended in tetrahydrofuran (1 mL) and 4-isopropyl-N- {2-methyl-6 - [(1-propionyl-pyrididin-3-yl) oxy] pyridin-3-yl } Benzenesulfonamide (250 mg) dissolved in tetrahydrofuran (1 mL) was added dropwise 40 at room temperature for 5 minutes. After stirring for another 30 minutes, the reaction was stopped with a 1% solution of water in tetrahydrofuran and then concentrated. The residue was taken in dichloromethane, washed with water and the organic phase was dried (sodium sulfate) and concentrated in vacuo. The crude product was purified by flash chromatography (silica, dichloromethane / methanol = 97/3). The product (70 mg) was dissolved in methanol and (2E) -but-2-enodioic acid (19 mg) was added. After stirring for 1 hour at 40 ° C methanol was removed in vacuo. 45 Yield: 89 mg (26%, colorless solid).

MS (ESI) m / z: 418.1 [M + H] +

EXAMPLE 62

4- (2-Fluoroethoxy) - N- {2-methyl-6 - [(1-propylpyrrolidin-3-yl) oxy] pyridin-3-yl} -benzenesulfonamide (2 E) -but-2-enedioate

4- (2-Fluoroethoxy) -N- {2-methyl-6 - [(1-propylpyrrolidin-3-yl) oxy] pyridin-3-yl} -benzenesulfonamide (2E) -but-2-enenedate was prepared analogous to example 61 from 2-methyl-6 - [(1-propionylpyrrolidin-3-yl) oxy] pyridin-3-amine and 4- (2-fluoroethoxy) benzenesulfonyl chloride.

MS (ESI) m / z: 438.1 [M + H] + 5

EXAMPLE 63

4- (2,2-Difluoroethoxy) - N- {2-methyl-6 - [(1-propylpyrrolidin-3-yl) oxy] pyridin-3-yl} -benzenesulfonamide (2 E) -but-2-enedioate

4- (2,2-Difluoroethoxy) -N- {2-methyl-6 - [(1-propylpyrrolidin-3-yl) oxy] pyridin-3-yl} -benzenesulfonamide (2E) -but-2-enedioate was prepared analogously to example 61 from 2-methyl-6 - [(1-propionylpyrrolidin-3-yl) oxy] pyridin-3-amine and 4- (2,2-difluoroethoxy) benzenesulfonyl chloride. 10

MS (ESI) m / z: 456.1 [M + H] +

EXAMPLE 64

4 - [(1 S) -2,2-Difluoro-1-methyl ethyl] - N- {2-methyl-6 - [(1-propylpyrrolidin-3-yl) -oxy] pyridin-3-yl} benzenesulfonamide (2 E) -but-2-Enedioate

4 - [(1 S) -2,2-Difluoro-1-methyl ethyl] -N- {2-methyl-6 - [(1-propylpyrrolidin-3-yl) -oxy] pyridin-3-yl} benzenesulfonamide

(2E) -but-2-enenedate was prepared analogously to example 61 from 2-methyl-6 - [(1-propionylpyrrolidin-3-yl) oxy] pyridin-3-amine and 4 - [(1S) -2,2-difluoro-1-methyl ethyl] benzenesulfonyl chloride.

MS (ESI) m / z: 454.1 [M + H] +

III. Examples of galenic forms of administration

A) Tablets 20

Tablets of the following composition are pressed on a tablet press in the usual way:

 40 mg

 of substance of Example 8

 120 mg

 cornstarch

 13.5 mg

 jelly

 45 mg

 lactose

 2.25 mg

 of Aerosil® (chemically pure silicic acid in submicroscopic fine dispersion)

 6.75 mg

 Potato starch (as a 6% paste)

B) Sugar coated tablets

20 mg of substance from example 8

60 mg of nuclear composition

70 mg saccharification composition 25

The nuclear composition consists of 9 parts of corn starch, 3 parts of lactose and one part of 60:40 vinylpyrrolidone / vinyl acetate copolymer. The saccharification composition consists of 5 parts of cane sugar, 2 parts of cornstarch, 2 parts of calcium carbonate and 1 part of talc. Sugar-coated tablets that have been prepared in this way are subsequently provided with a coating resistant to gastric juices.

IV. Biological Investigations 30

Studies of receptor binding:

The substance was tested well dissolved in methanol / Cremofor® (BASF-AG) or dimethyl sulfoxide and then diluted with water to the desired concentration.

D3 dopamine receptor

The test mixture (0.250 ml) was composed in a non-derivative manner from approximately 106 HEK-293 cells possessing stably expressed human dopamine D3 receptors, [125I]-0.1 nM sulpride iodine and 5 incubation regulator (binding) total) or, in addition, the test substance (inhibition curve) or 1µM spiperone (non-specific binding). Each test mixture was run in triplicate.

The incubation regulator contained 50 mM tris, 120 mM NaCl, 5 mM KCl, 2mM CaCl2, 2 mM MgCl2 and 0.1% bovine serum albumin, 10 µM quinolone and 0.1% ascorbic acid (fresh prepared daily). The regulator adjusted to pH 7.4 with HCl. 10

D2L dopamine receptor:

The test mixture (1 ml) was composed of membranes of approximately 106 HEK-293 cells possessing stably expressed human dopamine D2L receptors (long isoform) and 0.01 nM [125 I] iodospiperone and incubation regulator (total binding) or, in addition, test substance (inhibition curve) or 1µM aloperidol (non-specific binding). Each test mixture was run in triplicate. fifteen

The incubation regulator contained 50 mM tris, 120 mM NaCl, 5 mM KCl, 2mM CaCl2, 2 mM MgCl2, and 0.1% bovine serum albumin. The regulator was adjusted to pH 7.4 with HCl.

Measurement and Analysis:

After incubating at 25 ° C for 60 minutes, the test samples were filtered through a Whatman GF / B glass fiber filter under vacuum using a cell collection device. The filters were transferred to scintillation vials using a filter transfer system. After adding 4 ml of Ultima Gold® (Packard), the samples were shaken for 1 hour and the radioactivity was counted in a Beta-Counter (Packard, Tricarb 2000 or 2200 CA). The cpm values were converted to dpm using a standard stop series and the program belonging to the instrument.

The inhibition curves were analyzed by means of an iterative nonlinear regression analysis using the Statistical Analysis System (SAS) which is similar to the "LIGAND" program described by Munson and Rodbard.

Results of receptor binding studies are expressed as receptor binding constants Ki (D2) and (D3), respectively, as described hereinbefore, and are given in Table 3.

In these tests, the compounds according to the invention exhibit very good affinities for the D3 receptor (<10 nM, frequently <5 nM) and selectively bind to the D3 receptor. 30

The results of the binding tests are given in Table 1.

Table 1:

 Example

 Ki (D3) Ki (D2) ’/ Ki (D3) *

 one

 ++++ ++

 2

 +++ +

 3

 +++ ++

 4

 ++++ ++

 5

 +++ ++

 6

 +++ ++

 7

 ++++ ++++

 8

 +++ ++++

 Example

 Ki (D3) Ki (D2) ’/ Ki (D3) *

 9

 +++ ++++

 10

 +++ ++++

 eleven

 ++++ ++++

 13

 + +

 fifteen

 ++ +

 16

 +++ +

 17

 +++ ++

 18

 +++ +

 19

 ++ +

 twenty

 +++ +

 twenty-one

 + ++

 22

 + n.d.

 2. 3

 ++ +

 24

 ++ ++

 27

 +++ +++

 29

 ++++ ++++

 3. 4

 +++ ++++

 36

 ++ ++++

 43

 +++ +++

 57

 ++ ++

 61

 +++ +

 * Receiver binding constants obtained in accordance with the assays described here above.

Key:

 Ki (D3)

 +

 between 50 and 150 nM

 ++

 between 10 and 50 nM

 +++

 Between 1 and 10 nM

 Ki (D3)

 ++++

 <1 nM

 Ki (D2) * / Ki (D3) *

 +

 between 10 and 50

 ++

 between 50 and 100

 +++

 between 100 and 150

 ++++

 > 150

Claims (21)

1. An aryloxyethylamine compound of the formula 1

where 5 Ar is phenyl or a 5- or 6-membered heteroaromatic aromatic radical linked by C, where Ar can carry a Ra radical and where Ar can also carry 1 or 2 Rb radicals; Ra is selected from the group consisting of C1-C6 alkyl, fluorinated C1-C6 alkyl, C2-C6 alkenyl, C2-C6 fluorinated alkenyl, C3-C6 cycloalkyl, fluorinated C3-C6 cycloalkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy , C1-C6 hydroxyalkyl, C1-C4-C1-C6 alkoxy, C1-C6 hydroxyalkoxy, C1-C4 alkoxy-C1-C6 alkoxy, COOH, NR4R5, CH2NR4R5, ONR4R5, NHC (O) NR4R5, 10 C (O) NR4R5, SO2NR4R5, C1-C6 alkylcarbonyl, fluorinated C1-C6 alkylcarbonyl, C1-C6 alkylcarbonylamino, C1-C6 alkyl fluorinated amino carbonyl, C1-C6 alkylcarbonyloxy, C1-C6 alkyl fluorinated carbonyloxy, C1-C6 alkoxycarbonyl, fluorinated C1 -C6- alkoxycarbonyl, C1-C6 alkylthio, fluorinated C1-C6 alkylthio, C1-C6- alkylsulfinyl, C1-C6 alkyl fluorinated sulfinyl, C1-C6 alkyl sulfonyl, C1-C6 alkyl fluorinated sulfonyl, phenylsulfonyl, phenyl, phenoxy, benzyloxy, pyridin-2-yloxy and a 3- to 7-membered heterocyclic radical, where the phenyl groups, the pyridyl group and the heterocyclyl group in the last six radicals mentioned you can carry 1, 2, 3 or 4 radicals selected from halogen, cyano, OH, oxo, CN, and a Raa radical, where Raa is selected from C1-C6 alkyl, fluorinated C1-C6 alkyl, C2-C6 alkenyl, C2-C6 fluorinated alkenyl, C3-C6 cycloalkyl, fluorinated C3-C6 cycloalkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy, C1 hydroxyalkyl -C6, C1-C6-C1-C4 alkoxy-alkyl, C1-C6 hydroxyalkoxy, C1-C4 alkoxy-C1-C6 alkoxy, COOH, NR4R5, CH2NR4R5, ONR4R5, NHC (O) NR4R5, C (O) NR4R5, 20 SO2NR4R5, C1-C6 alkylcarbonyl, C1-C6 alkyl fluorinated carbonyl, C1-C6 alkylcarbonylamino, C1-C6 alkylcarboxylated amino, C1-C6 alkylcarbonyloxy, C1-C6 alkyl fluorinated carbonyloxy, C1-C6 alkoxycarbonyl, C1-C6 fluorinated alkoxycarbonyl, C1-C6 alkylthio, fluorinated C1-C6 alkylthio, C1-C6 alkyl sulfinyl, C1-C6 alkyl fluorinated sulfinyl, C1-C6 alkyl sulfonyl, C1-C6 alkyl fluorinated sulfonyl, each Rb is selected from halogen, cyano, nitro, OH, methyl, methoxy, fluoromethyl, difluoromethyl, trifluorome tyl, fluoromethoxy, difluoromethoxy and trifluoromethoxy, or the Ra radical and an Rb radical, if present, which are linked to two adjacent carbon atoms of phenyl, can form a 5- or 6-membered heterocyclic or carbocyclic ring which is fused to the phenyl ring and which is unsubstituted or it may carry 1, 2 or 3 selected roots of halogen, NO2, NH2, OH, CN, C1-C6 alkyl, fluorinated C1-C6 alkyl, C3-C6 cycloalkyl, fluorinated C3-C6 cycloalkyl, C1-C6 alkoxy, C1 alkoxy -C6 fluorinated, Hydroxyalkyl C1-C6, C1-C4-alkoxy-C2-C4-alkyl, Hydroxyalkoxy C1-C6, C1-C4-alkoxy-C2-C4-alkoxy, C1-C6 alkylcarbonyl, C1-C6 alkylcarbonyl fluorinated, C1-C6-alkyl, di-C1-C6-alkyl, C1-C6-alkylcarbonyl, di-C1-C6-alkylcarbonyl, C1-C6-alkylcarbonylamino, C1-C6 alkyl, fluorinated amino-carbon, C1-C6-alkylcarbonyloxy, C1-C6-alkyl-carbonyl fluorinated, C1-C6 alkoxy carbonyl, C1-C6 alkylthio, fluorinated C1-C6 alkyl, C1-C6 alkyl sulfinyl, C1-C6 alkyl fluorinated sulfinyl, Alkyl C1-C6 sulfonyl and C1-C6 alkyl fluorinated sulfonyl, X is N or CH; 35 R1 is H, C1-C4-alkyl, C3-C4-cycloalkyl, C3-C4-cycloalkylmethyl, C3-C4-alkenyl, fluorinated C1-C4 alkyl, fluorinated C3-C4 cycloalkyl, fluorinated C3-C4 cycloalkylmethyl, C3-C4 alkenyl fluorinated, formyl or C1-C3-alkylcarbonyl; R1a is H, C1-C4-alkyl, C3-C4-cycloalkyl, C3-C4-cycloalkylmethyl, C3-C4-alkenyl, fluorinated C1-C4 alkyl, fluorinated C3-C4 cycloalkyl, or C3- alkenyl C3- Fluorinated C4; or R1 and R1a together are (CR6R7) r being r 3, 4 or 5; 40 R2 and R2a are independently of each other H, fluorine, C1-C4-alkyl or fluorinated C1-C4 alkyl or R2a and R2 together can form a ring member (CR6R7) m being m 2, 3, 4 or 5; or R1a and R2a together are (CR6R7) n being n 2, 3 or 4, R3 is H or C1-C4-alkyl; R4, R5 independently of each other and regardless of their individual frequency are selected from H, C1-C3-alkyl, C1-C3-alkoxy and fluorinated C1-C3 alkyl; R6, R7 independently of each other and regardless of their individual frequency are selected from H, fluorine, C1-C4-alkyl and fluorinated C1-C4 alkyl; 5 R8, R8a independently of each other are H, fluorine, C1-C4-alkyl or fluorinated C1-C4 alkyl or R8a and R8 together can form a ring member (CR6R7) q being q 2, 3, 4 or 5; or R1a and R8a together are (CR6R7) s being s 2 or 3; R9 is H, C1-C4-alkyl, fluorinated C1-C4 alkyl, C1-C4-alkoxy or fluorinated C1-C4 alkoxy; and the physiologically tolerated acid addition salts of these compounds. 10

2. The compound as claimed in claim 1 wherein Ar is phenyl or a 5- or 6-membered heteroaromatic aromatic radical joined by C, comprising a nitrogen atom as a ring member and 0, 1, 2 or 3 additional heteroatoms selected O, S and N as ring members, where Ar carries a radical Ra which is selected from the group consisting of C1-C6 alkyl, fluorinated C1-C6 alkyl, C3-C6 cycloalkyl, fluorinated C3-C6 cycloalkyl, C1- alkoxy C6, fluorinated C1-C6 alkoxy, NR4R5, 1-aziridinyl, azetidin-1-yl, pyrrolidin-1-yl, piperidin-1-yl, where the last four radicals 15 can be fluorinated, a phenyl group and a heteroaromatic radical of 5 or 6 members linked via C comprising a nitrogen atom as a ring member and 0, 1, 2 or 3 additional heteroatoms selected from O, S and N as ring members, where the last two mentioned radicals can carry 1, 2 , 3 or 4 radicals selected from halogen and a Raa radical, where Raa is selected from C1-C6 alkyl, fluorinated C1-C6 alkyl, C3-C6 cycloalkyl, fluorinated C3-C6 cycloalkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy and NR4R5; and where Ar can carry 1 or 2 additional radicals Rb, which are independently from each other selected from halogen, cyano, methyl, fluoromethyl, difluoromethyl, trifluoromethyl, difluoromethoxy and trifluoromethoxy; and where R4, R5, independently of each other and independently of each individual frequency, are selected from H, C1-C3-alkyl and fluorinated C1-C3 alkyl.

3. The compound as claimed in claims 1 or 2, wherein Ar carries a Ra radical of the formula Ra ’

 25 where Y is N, CH or CF, Ra1 and Ra2 are independently from each other selected from C1-C2-alkyl, C1-C2-alkoxy, fluorinated C1-C2 alkyl, assuming that when Y is CH or CF one of the radicals Ra1 or Ra2 may also be hydrogen or fluorine, or Ra1 and Ra2 together form a ring member (CH2) k where 1 or 2 of the hydrogen atoms can be replaced by fluorine, hydroxy, oxo, C1-C2-alkyl or C1-C2-alkoxy, and where a structural unit CH2 can be replaced by O, S, S = O, SO2 or NRc, with Rc, when they are hydrogen or C1-C2-alkyl, and where k is 2, 3, 4, 5 or 6.

4. The compound as claimed in claim 3, wherein the radical Ra 'is selected from isopropyl, (R) -1-fluoroethyl, (S) -1-fluoroethyl, 2-fluoroethyl, 1,1-difluoroethyl, 2, 2-Difluoroethyl, 2,2,2-trifluoroethyl, (R) -1-fluoropropyl, (S) -1-fluoropropyl, 2-fluoropropyl, 3-fluoropropyl, 1,1-difluoropropyl, 2,2-difluoropropyl, 3, 3-difluoropropyl, 3,3,3-35 trifluoropropyl, (R) -2-fluoro-1-methyl ethyl, (S) -2-fluoro-1-methyl ethyl, (R) -2,2-difluoro-1-methyl ethyl , (S) -2,2-difluoro-1-methylethyl, (R) -1,2-difluoro-1-methylethyl, (S) -1,2-difluoro-1-methylethyl, (R) -2,2 , 2-Trifluoro-1-methyl ethyl, (S) -2,2,2-trifluoro-1-methyl ethyl, 2-fluoro-1- (fluoromethyl) ethyl, 1- (difluoromethyl) -2,2-difluoroethyl, cyclopropyl, cyclobutyl, 1-fluorocyclopropyl, and 2-fluorocyclopropyl.

5. The compound as claimed in claim 1 wherein Ar is unsubstituted or carries a Ra radical, which is selected from the group consisting of (CH2) vCF3, (CH2) vCHF2, (CH2) vCH2F, O (CH2) vCF3, O (CH2) vCHF2 and O (CH2) vCH2F, where v 0, 1, 2 or 3.

6. The compound as claimed in claim 1, wherein Ar carries a heteroaromatic radical Ra, which is selected from furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, Isoxazolyl, [1,3,4] -thiadiazolyl, [ 1,2,4] -triazolyl,

[1,2,3] -triazolyl and tetrazolyl, where the heteroaromatic radical may be unsubstituted or may carry 1 to 3 substituents selected from halogen, C1-C4-alkyl, C1-C4-alkoxy, fluorinated C1-C4 alkyl and alkoxy C1-C4 fluorinated.

7. The compound as claimed in any of the preceding claims, wherein Ar is phenyl.

8. The compound as claimed in claim 7, wherein Ar carries a Ra radical at position 4 of the phenyl ring. 5

9. The compound as claimed in any of the preceding claims, wherein R9 is Hydrogen, methoxy or methyl.

10. The compound as claimed in any preceding claim, wherein R1 is H, methyl, n-propyl, fluorinated C2-C3 alkyl or 1-propen-3-yl.

11. The compound as claimed in any of the preceding claims, wherein R1a is Hydrogen or C1-10 C4-alkyl.

12. The compound as claimed in any of the preceding claims, wherein R2a is Hydrogen.

13. The compound as claimed in any of the preceding claims, wherein R2 is Hydrogen.

14. The compound as claimed in any of the preceding claims, wherein R8a is Hydrogen.

15. The compound as claimed in any of the preceding claims, wherein R8 is Hydrogen. fifteen

16. The compound as claimed in any one of claims 1 to 10 and 13-15, wherein R2a and R1a together form an alkylene group (CH2) n being n 2, 3 or 4.

17. The compound as claimed in any one of claims 1 to 10, 12, 13 or 15, wherein R8a and R1a together form an alkylene group (CH2) to be s 2 or 3.

18. The compound as claimed in any of the preceding claims, wherein R1a, R2, R2a, R8 and R8a are each H, R1 is propyl, R9 is methoxy or methyl and Ar is as defined in any of the claims 1 to 8

19. A pharmaceutical composition comprising at least one compound of the formula 1 or a pharmaceutically acceptable salt as claimed in any one of the preceding claims, optionally together with at least one vehicle or a physiologically acceptable auxiliary substance.

20. The use of a compound of the formula 1 or a pharmaceutically acceptable salt thereof as claimed in any one of the preceding claims 1 to 18 to prepare a pharmaceutical composition for the treatment of a medical disorder susceptible to treatment with a ligand. of the dopamine D3 receptor.

21. The use as claimed in claim 20, wherein the medical disorder is a disease of the central nervous system.