NO862477L - ANALOGY PROCEDURE FOR THE PREPARATION OF THERAPEUTIC ACTIVE 2-ARYLIMIDAZOLE DERIVATIVES. - Google Patents

Description

This invention relates to a process for the preparation of new 2-arylimidazoles with the general formula

and tautomers thereof when R means a hydrogen atom, as well as connecting

tendon

5-cyano-2-(4<1->methanesulfonylamino-2'methoxy-phenyl)-benz-

imidazole,

4-methyl-2-(4<1->methanesulfonyloxy-2-methoxy-phenyl)-benz-

imidazole,

4-cyano-2-(4'-methanesulfonyloxy-2'-methoxy-phenyl)-benz-

imidazole,

4-aminocarbonyl-2-(4<1->methanesulfonyloxy-2'-methoxy-phenyl-

benzimidazole and

4-Methoxycarbonyl-2-(4'-methanesulfonyloxy-2<1->methoxy-phenyl)-benzimidazole

and their acid addition salts, especially their physiological

equal acid addition salts with inorganic and organic acids.

The new compounds and their physiologically compatible acid addition salts exhibit valuable pharmacological properties

creates, in particular, an effect on blood pressure and on the contractility of the heart muscle as well as antithrombotic effects. The compounds produced according to the invention can be used in medicines which are suitable for the treatment of heart insufficiency of various origins, for the treatment and for the prevention of thrombo-

embolic disorders, for the prevention of arteriosclerosis and for metastasis prevention.

In the above general formula I means

R a hydrogen atom or an alkyl group,

Ar is a group with the formula

A and B together with the two intermediate carbon atoms form a group with the formula

where

means an alkylsulfenyl, alkylsulfinyl, alkylsulfonyl

or alkylsulfoximino group, an alkylsulfoximino group substituted on the nitrogen atom with an alkanoyl, alkylsulfonyl or hydroxycarbonylalkylenecarbonyl group, an ethoxy or n-propoxy group, which is substituted in the terminal position with an alkylsulfenyl, alkylsulfinyl, alkylsulfonyl or alkylsulfoximino group, an alkoxycarbonylamino- or N-alkylaminocarbonylamino group or also in the 4-position a hydroxy, phenylalkoxy, aminosulfonyl, alkylsulfonyloxy or alkylsulfonylamino group, when

a) A and B together with the 2 intermediate carbon atoms are one

b) R 4 is an alkyl-, alkanoyl-, N-alkanoyl-aminomethyl-, benzoyl-, phenyl-methoxymethyl-, aminosulfonyl-, N-ethylaminocarbonyl-amino-, N-n-propylaminocarbonyl-amino-, N-isopropylaminocarbonylamino- or N-alkyl -N-alkylaminocarbonylamino group or c) R,b, is an amino group, as at least one of the residues must have the meanings specified under a), b) and c),

R2 means a hydrogen atom or an alkoxy group,

R3 means an ethoxy or n-propoxy group, each of which is substituted in the terminal position with an alkylsulfenyl, alkylsulfinyl, alkylsulfonyl or alkylsulfoximino group, means an alkyl, alkoxycarbonyl, alkanoyl, N-alkanoyl-aminomethyl, benzoyl, phenylmethoxymethyl -, aminocarbonyl, cyano, trifluoromethyl, aminosulfonyl, N-alkylaminocarbonylamino or N-alkyl-N-alkylaminocarbonylamino group,

R,- means a hydrogen or halogen atom, an alkyl or cyano group, and

Rg means a hydrogen atom or an amino group, provided that a) R^ does not mean an alkyl mercapto group in the 4-position when Rg means a hydrogen atom or R^ in the 5-position a methoxycarbonyl, aminocarbonyl or cyano group and at the same time R2 in 2- position a methoxy or ethoxy group and R a hydrogen atom,

b) R^ does not mean an alkylsulfinyl group in the 4-position, when Rg means a hydrogen atom or R^ in the 5-position a cyano- or

aminocarbonyl group and at the same time R2 in 2-position a methoxy or ethoxy group and R a hydrogen atom,

c) R^ does not mean an alkylsulfonyl group in the 4-position, when Rg means a hydrogen atom or R^ in the 5-position a cyano- or

aminocarbonyl group and at the same time R2i 2 position a methoxy

or ethoxy group and R a hydrogen atom,

d) R^ does not mean an alkylsulfoximino group in the 4-position,

when R^ in the 5-position means a cyano or carbamido group and

at the same time R 2 in 2 position a methoxy or ethoxy group and R a hydrogen atom, or

e) R-^in 4-position does not mean a hydroxy or phenyl-alkoxy group, when Rg means a hydrogen atom or R^in 5-position

a methoxycarbonyl, aminocarbonyl or cyano group and at the same time R2i 2-position a methoxy or ethoxy group and R a hydrogen atom,

in that the above-mentioned alkyl, alkylene, alkoxy and alkanoyl parts can in each case contain 1-3 carbon atoms.

For the definitions of the residues R and R-^ to Rg given at the beginning, e.g. whereas for R the meaning is a hydrogen atom, a methyl, ethyl, n-propyl or isopropyl group,

for R^ the meaning of a methylmercapto-, ethylmercapto-, n-propyl-mercapto-, methylsulfinyl-, ethylsulfinyl-, isopropylsulfinyl-, methylsulfonyl-, ethylsulfonyl-, n-propylsulfonyl-, methylsulfoximino-, ethylsulfoximino-, isopropylsulfoximino-, N-acetyl-

methylsulfoximino-, N-propionyl-methylsulfoximino-, N-methanesulfonyl-methylsulfoximino-, N-ethanesulfonyl-methylsulfoximino-, N-hydroxycarbonylmethylenecarbonyl-methylsulfoximino-, N-(2-hydroxycarbonyl-ethylenecarbonyl)-methylsulfoximino-, N-(3-hydroxycarbonyl) 1-propylenecarbonyl)-methylsulfoximino-, N-acetyl-ethylsulfoximino-, N-methanesulfonyl-ethylsulfoximino-, N-acetyl-n-propylsulfoximino-, 2-methylmercaptoethoxy-, 2-isopropyl-mercaptoethoxy- , 2-methylsulfinylethoxy-, 2-methylsulfonylethoxy-, 2-methylsulfoximinoethoxy-, 3-methylmercapto-n-propoxy-,3-methylsulfinyl-n-propoxy-, 3-methylsulfonyl-n-propoxy-, 3-methylsulfoximino-n- propoxy-, methoxycarbonylamino-, ethoxycarbonyl-amino-, n-propoxycarbonylamino-, N-methylaminocarbonylamino-, N-ethylaminocarbonylamino-, N-isopropylaminocarbonyl-, hydroxy-, benzyloxy-, 1-phenylethoxy- , 2-phenylethoxy-, 3-phenylpropoxy-, aminosulfonyl-, methylsulfonyloxy-, ethylsulfonyloxy-, n-propylsulfonyloxy-, methanesulfonylami.no-, ethanesulfonyl ami.no- or propanesulfonylamino group,

for R_ meaning a hydrogen atom, a methoxy, ethoxy, n-propoxy or isopropoxy group,

for the R meaning a 2-methylmercaptoethoxy-, 2-ethylmercaptoethoxy-, 2-n-propylmercaptoethoxy-, 2-methylsulfinylethoxy-, 2-isopropylsulfinylethoxy-, 2-methylsulfonylethoxy-, 2-ethylsulfonylethoxy-, 2-methylsulfoximinoethoxy-, 2-ethylsulfoximinoethoxy-, 2-n-propylsulfoximinoethoxy-, 3-methylmercaptopropoxy-, 3- ethylmercaptopropoxy-, 3-n-propylmercaptopropoxy-, 3-methylsulf i.nylpropoxy-, 3-isopropylsulfinylpropoxy-, 3 -methylsulfonylpropoxy, 3-ethylsulfonylpropoxy, 3-methylsulfoximinopropoxy, 3-ethylsulfoximinopropoxy or 3-n-propylsulfoximinopropoxy group,

for the R4 meaning a methyl-, ethyl-, n-propyl-, methoxycarbonyl-, ethoxycarbonyl-, isopropoxycarbonyl-, acetyl-, propionyl-, benzoyl-, N-acetyl-aminomethyl-, N-propionyl-aminomethyl-, phenyl- methoxymethyl-, aminocarbonyl-, cyano-, trifluoromethyl-, amino-sulfonyl-, N-methylaminocarbonyl-amino-, N-ethylaminocarbonyl-amino-, N-n-propylaminocarbonyl-amino-, N-isopropylaminocarbonyl-amino-, N-methyl- N-methylaminocarbonyl-amino-, N-ethyl-N-ethylamino.no-carbonyl-amino-, or N-methyl-N-ethylaminocarbonyl-amino group, for R^ meaning a hydrogen, fluorine, chlorine or bromine atom , a cyano, methyl, ethyl, n-propyl or isopropyl group, and

for Rg meaning a hydrogen atom or an amino group.

Preferred compounds of the above general formula I are those wherein

R means a hydrogen atom or a methyl group,

R1 denotes a methylsulfenyl, ethylsulfenyl, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl, methylsulfoximino, ethylsulfoximino or n-propylsulfoximino group, a methylsulfoximino group substituted on the nitrogen atom with an acetyl-, methanesulfonyl- or hydroxycarbonyl-ethylenecarbonyl group , an ethoxy group substituted at the end with a methylsulfoximino group, a methoxycarbonylamino- or N-methylamino-carbonylamino group or also in the 4-position a hydroxy-, benzyloxy-, aminosulfonyl, methanesulfonyloxy or methanesulfonylamino group, when

a) A and B together with the two intervening carbon atoms means one

b) R4 represents a methyl-, acetyl-, N-acetyl-aminomethyl-, benzoyl-, phenylmethoxymethyl-, aminosulfonyl-, N-ethylaminocarbonylamino-, N-isopropylaminocarbonylamino- or N-methyl-N-methylaminocarbonyl- amino group, or

c) Rg means an amino group,

as at least one of the residues must have those under a), b) and c)

stated meanings,

R2 means a hydrogen atom, a methoxy or an ethoxy group, R3 means an ethoxy group which is ultimately substituted with a methylsulfenyl, methylsulfinyl, methylsulfonyl or methylsulfoximino group,

R4 means a methyl-, methoxycarbonyl-, acetyl-, N-acetylamino-methyl-, benzoyl-, phenylmethoxymethyl-, aminocarbonyl-, cyano-, trifluoromethyl-, aminosulfonyl-, N-ethylaminocarbonyl-amino-, N-isopropylaminocarbonyl-amino- or N-methyl-N-methylaminocarbonyl-amino group,

R,- means a hydrogen or chlorine atom, a methyl or cyano group and

Rg means a hydrogen atom or an amino group, provided that

a) R^ does not mean a methyl or ethyl mercapto group in the 4-position when Rg means a hydrogen atom or R^ in the 5-position a

methoxycarbonyl, aminocarbonyl or cyano group and at the same time R2 in the 2-position a methoxy or ethoxy group and R a hydrogen atom,

b) R^ does not mean a methyl or ethylsulfinyl group in the 4-position when Rg means a hydrogen atom or R^ in the 5-position

a cyano or aminocarbonyl group and at the same time R 2 in 2 position a methoxy or ethoxy group and R a hydrogen atom,

c) R^ does not mean a methyl or ethylsulfonyl group in the 4-position when Rg means a hydrogen atom or R^ in the 5-position a

cyano or aminocarbonyl group and at the same time R2i 2 position a methoxy or ethoxy group and R a hydrogen atom, d) R^ does not mean a methyl or ethylsulfoximino group in the 4-position when R4i 5-position means a cyano or carbamido group and at the same time R2i 2 -position a methoxy or ethoxy group and R a hydrogen atom, or e) R-^i 4-position does not mean a hydroxy or benzyloxy group when Rg means a hydrogen atom or R^i 5-position a

methoxycarbonyl, aminocarbonyl or cyano group and at the same time R2 in the 2-position a methoxy or ethoxy group and R a hydrogen atom, as well as the compounds

5-cyano-2-(4'-methanesulfonylamino-2'-methoxy-phenyl)-benzimidazole,

4-methyl-2-(4'-methanesulfonyloxy-2<1->methoxy-phenyl)-benzimidazole,

4-cyano-2-(4'-methanesulfonyloxy-2'-methoxy-phenyl)-benzimidazole,

4-aminocarbonyl-2-(4<1->methanesulfonyloxy-2<1->methoxy-phenyl)-benzimidazole and

4-methoxycarbonyl-2-(4<1->methanesulfonyloxy-2<1->methoxy-phenyl)-benzimidazole,

their tautomers and their acid addition salts, especially their physiologically compatible acid addition salts.

Particularly preferred compounds of the general formula

I is 2-[2'-methoxy-4'-(N-acetyl-methylsulfoximino-phenyl)]-5-cyano-benzimidazole

2-(2'-Methoxy-4'-methylsulfonyl-phenyl)-5-acetyl-benzimidazole, 2-(2'-Methoxy-4'-methylsulfonyl-phenyl)-5-acetyl-benzimidazole, 5- cyano-2- (4'-methanesulfonylamino-2'-methoxyphenyl)-benzimidazole, 2-(2<1->methoxy-4'-methoxycarbonylamino-phenyl)-imidazo[4,5-c]-pyridine,

6- cyano-2-(2'-methoxy-4-methylmercapto-phenyl)-imidazo[4,5-b]-pyridine,

2-amino-8-(2'-methoxy-4<1->methylsulfinyl-phenyl)-purine, 2-(2'-methoxy-4'-methylsulfoximino-phenyl)-1H-imidazo[4,5-c] -pyridine,

5-aminocarbonyl-2-(4'-methanesulfonyloxy-2<1->methoxy-phenyl)-benzimidazole and

5-Acetyl-2-(4<1->methanesulfonyloxy-2'-methoxy-phenyl)-benzimidazole, their tautomers and their acid addition salts, especially their physiologically compatible acid addition salts.

According to the invention, the new compounds are produced by the following methods: a) ring closure of a compound with the general formula possibly produced in the reaction mixture

where

A, B and R are, as indicated at the outset,

one of the residues X or Y means a hydrogen atom and the other of the residues X and Y or both residues X and Y means a group with the formula

Ar is, as stated at the outset,

Z^ and Z 2 , which may be the same or different, mean optionally substituted amino groups or optionally substituted with lower alkyl groups hydroxy or mercapto groups, or and Z 2 together mean an oxygen or sulfur atom, one optionally substituted with an alkyl group with 1-3 carbon atoms imino group, an alkylenedioxy or alkylenedithio group each having 2 or 3 carbon atoms.

The cyclization is conveniently carried out in a solvent or a solvent mixture such as ethanol, iso-propanol, glacial acetic acid, benzene, chlorobenzene, toluene, xylene, glycol, glycol monomethyl ether, diethylene glycol dimethyl ether, sulfolane, dimethylformamide, tetralin or in an excess thereof for the production of the compound with the general formula II used acylating agent, e.g. in the appropriate nitrile, anhydride, acid halide, ester, amide or methoiodide, e.g. at temperatures between 0 and 250°C, preferably at the boiling temperature of the reaction mixture, optionally in the presence of a condensing agent such as phosphorus oxychloride, thionyl chloride, sulfuryl chloride, sulfuric acid, p-toluenesulfonic acid, methanesulfonic acid, hydrochloric acid, phosphoric acid, polyphosphoric acid, acetic anhydride or optionally also in the presence of a base such as potassium ethylate or potassium tert-butylate. The cyclization can also be carried out without solvent and/or condensing agent. b) For the preparation of compounds with the general formula I where R^ denotes an alkylsulfonyl, alkylsulfonyl or alkylsulfoximino group, an alkylsulfoxy monogroup substituted on the nitrogen atom with an alkanoyl, alkylsulfonyl or hydroxycarbonylalkylenecarbonyl group, an ethoxy or n-propoxy group, which is substituted in the terminal position with an alkylsulfinyl, alkylsulfonyl or alkylsulfoximino group, or R^ an ethoxy or n-propoxy group which is substituted in the terminal position with an alkylsulfinyl, alkylsulfonyl or alkylsulfoximino group: oxidation of a compound of the general formula

where K

A, B and R are as stated at the outset, and

Ar-^ has the meanings given for Ar at the beginning, with R^, however, meaning an alkylsulfinyl, alkylsulfinyl or alkylsulfimino group, an alkylsulfimino group substituted on the nitrogen atom with an alkanoyl, alkylsulfonyl or hydroxycarbonylalkylenecarbonyl group, an ethoxy or n-propoxy group, as in end position is substituted with an alkylsulfenyl, alkylsulfinyl or alkylsulfimino group, or R., an ethoxy or n-propoxy group, which is substituted at the end position with an alkylsulfenyl, alkylsulfinyl or alkylsulfimino group.

The oxidation is preferably carried out in a solvent or a solvent mixture, e.g. in water, water/pyridine, acetone, glacial acetic acid, dilute sulfuric acid or trifluoroacetic acid, depending on the oxidizing agent used, suitably at temperatures between -80 and 100°C.

For the preparation of an alkylsulfinyl or sulfoxymino compound with the general formula I, the oxidation is suitably carried out with an equivalent of the oxidizing agent used, e.g. with hydrogen peroxide in glacial acetic acid, trifluoroacetic acid or formic acid at 0-20°C or in acetone at 0-60°C, with a peracid such as permauric acid in glacial acetic acid or trifluoroacetic acid at 0-50°C, or with m-chloroperbenzoic acid in methylene chloride or chloroform at -20-60°C, with sodium metaperiodate in aqueous methanol or ethanol at -15-25°C, with bromine in glacial acetic acid or aqueous acetic acid, with N-bromosuccinimide in ethanol, with tert-butyl hypochlorite in . methanol at -80 to -30°C, with iodobenzodichloride in aqueous pyridine at 0-50°C, with nitric acid in glacial acetic acid at 0-20°C, with chromic acid in glacial acetic acid or in. acetone at 0-20°C and with sulfuryl chloride in methylene chloride at -70°C, the thioether-chlorine complex thus obtained being suitably hydrolysed with aqueous ethanol.

For the preparation of an alkylsulfonyl compound of the general formula I, the oxidation is suitably carried out with one resp. with two or more equivalents of the oxidizing agent used, e.g. with hydrogen peroxide in glacial acetic acid, trifluoroacetic acid or in formic acid at 20-100°C or in acetone at 0-60°C, with a peracid such as performic acid or m-chloroperbenzoic acid in glacial acetic acid, trifluoroacetic acid, methylene chloride or chloroform at temperatures between 0 and 60°C, with nitric acid in glacial acetic acid at 0-20°C, with chromic acid or potassium permanganate in glacial acetic acid, water/sulfuric acid or in. acetone at 0-20°C.

c) For the preparation of compounds of the general formula I, where R^ denotes an alkylsulfoximino group, an ethoxy- or

n-propoxy group, which is substituted in the terminal position with an alkylsulfoximino group, or R^an ethoxy or n-propoxy group which is substituted in the terminal position with an alkylsulfoximino group:

reaction of a sulfoxide with the general formula

where

A, B and R are as stated at the outset, and

Ar2 has the meanings given for Ar at the beginning,

where, however, R^ is an alkylsulfinyl group, an ethoxy or n-propoxy group which is substituted in the end position with an alkylsulfinyl group, or R^ an ethoxy or n-propoxy group which is substituted in the end position with an alkylsulfinyl group, possibly with hydrogen azide formed in the reaction mixture .

The reaction is conveniently carried out in a solvent or a solvent mixture such as methylene chloride, dimethylformamide or tetrahydrofuran, at temperatures between 0 and 40°C, preferably at temperatures between 10 and 35°C. It is particularly advantageous to carry out the reaction with an alkali azide, e.g. sodium azide, and polyphosphoric acid as solvent.

d) For the preparation of compounds with the general formula I where R^ means an alkylsulfoximino group, an ethoxy or n-propoxy group which is substituted in the end position with an alkylsulfoximino group, or R^ an ethoxy or n-propoxy group which is substituted in the end position with an alkylsulfoximino group: reaction of a sulfoxide of the general formula

where

A, B and R are as stated at the outset, and

Ar2here the meanings given for Ar at the beginning,

where, however, R^ means an alkylsulfinyl group, an ethoxy or n-propoxy group which is substituted in the end position with an alkylsulfinyl group, or R^ an ethoxy or n-propoxy group which is substituted in the end position with an alkylsulfinyl group, with a compound possibly produced in the reaction mixture with the general formula

where

U means a carbonyl or sulfonyl group and

R.^ an aryl group disubstituted in the o-position such as a 2,4,6-trimethylphenyl or 2,4,6-triisopropylphenyl group.

The reaction is suitably carried out in a solvent or a solvent mixture such as methylene chloride, chloroform, dimethylformamide, tetrahydrofuran or dioxane, at temperatures between 0 and 50°C, preferably at temperatures between 5 and 40°C, and optionally in the presence of a catalytic amount of an acid such as p-toluenesulfonic acid. However, the conversion is particularly advantageous by using a compound of the general formula V without prior isolation or is produced in the reaction mixture. e) For the preparation of a compound of the general formula I, where R^ denotes an alkylsulfoximino group substituted on the nitrogen atom with an alkanoyl, alkylsulfonyl or hydroxycarbonylalkylenecarbonyl group:

acylation of a compound of the general formula

where

A, B and R are as stated at the outset, and

Ar^ have the meanings indicated for Ar at the beginning,

however, R-^ means an alkylsulfoximino group, with a

connection with the general formula

where

Rg means an alkanoyl, alkylsulfonyl or hydroxycarbonyl-alkylenecarbonyl group and

V is a nucleofuge leaving group such as a halogen atom or an alkanoyloxy group, or its esters and anhydrides.

The reaction is suitably carried out in a solvent or solvent mixture such as water, methylene chloride, chloroform, ether, tetrahydrofuran, dioxane or dimethylformamide, with a suitable compound in the presence of an acid-activating or water-attracting agent such as thionyl chloride, with anhydrides such as acetic anhydride, with esters such as acetic acid ethyl ester, with halides such as acetyl chloride or methanesulfonyl chloride, optionally in the presence of an inorganic or tertiary organic base such as sodium hydroxide, potassium carbonate, triethylamine or pyridine, the two latter at the same time also serving as a solvent, at temperatures between -25 and 100 °C, preferably at temperatures between -10 and 80°C. f) For the preparation of compounds of the general formula I where R^ means an alkylsulfonyloxy-, alkylsulfonylamino-, alkoxycarbonylamino- or N-alkylaminocarbonyl-amino group or R^ an alkanoylaminomethyl-, N-ethylaminocarbonylamino-, N-n- propylaminocarbonylamino, N-isopropylaminocarbonylamino or N-alkyl-N-alkylaminocarbon<y>1-amino group:

acylation of a compound of the general formula

where

A, B and R are as indicated at the beginning, and Ar^ has the meanings indicated for Ar at the beginning, with R^ meaning a hydroxy or amino group or R. an aminomethyl or amino group, with a compound of the general formula

where

Rg means an alkyl group with 1-3 carbon atoms and

W an O=N=C- or halosulfonyl group such as a chloro or bromosulfonyl group, or

Rg means a methyl or ethyl group and

W a -CO-V group, where V means a nucleofuge leaving group

such as a halogen atom or an alkanoyloxy group.

The reaction is conveniently carried out in a solvent or a solvent mixture such as methylene chloride, chloroform, carbon tetrachloride, ether, tetrahydrofuran, dioxane, benzene, toluene, acetonitrile or dimethylformamide, optionally also in the presence of an acid-activating agent or a water-attracting agent, e.g. . in the presence of chloroformate ethyl ester, thionyl chloride, phosphorus trichloride, phosphorus pentoxide, N,N<1->dicyclohexylcarbodiimide, N,N<1->dicyclohexylcarbodiimide/N-N-hydroxysuccinimide, N,N<1->carbonyldiimidazole or N,N<1- >thionyldiimidazole, and optionally in the presence of an inorganic base such as sodium carbonate or a tertiary organic base such as triethylamine or pyridine, the latter both of which can also serve as a solvent, at temperatures between -25 and 250°C, preferably at temperatures between -10° C

and the boiling point of the solvent used.

g) For the preparation of compounds of the general formula I where R means an alkyl group:

alkylation of a compound of the general formula

where

A, B and Ar are as initially indicated.

The reaction is carried out with a suitable alkylating agent such as methyl iodide, ethyl iodide, diethyl sulphate, dimethyl sulphate or n-propyl bromide, suitably in a solvent or a solvent mixture such as methylene chloride, ether, tetrahydrofuran, dioxane, water or benzene, optionally in the presence of an acid-binding agent such as sodium carbonate, sodium hydroxide, triethyl amine or pyridine, the two latter can also be used as a solvent at the same time, preferably at temperatures between 0 and 100°C, e.g. between room temperature and 50°C.

If, according to the invention, a compound with the general formula I is obtained where R means a benzyloxy group, this can be transferred by debenzylation to the corresponding hydroxy compound, and/or

a prepared compound of the general formula I where R 1 means a cyano group can be transferred by hydrolysis to the corresponding aminocarbonyl compound.

The subsequent debenzylation is preferably carried out in a solvent such as water, water/ethanol, methanol, glacial acetic acid, ethyl acetate or dimethylformamide, suitably with hydrogen in the presence of a hydrogenation catalyst such as Raney nickel, platinum or palladium/charcoal, at temperatures between 0 and 50°C , preferably at room temperature.

The subsequent hydrolysis is carried out in the presence of an inorganic base with hydrogen peroxide, e.g. with 2N caustic soda or caustic soda/hydrogen peroxide, at temperatures between 0 and 50°C, preferably at room temperature.

The new compounds produced according to the invention can then optionally be transferred to their acid addition salts. The compounds thus obtained can also be transferred for pharmaceutical use to their physiologically compatible acid addition salts. As acids, e.g. considering hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, fumaric acid, succinic acid, tartaric acid, citric acid, lactic acid, maleic acid or methanesulfonic acid.

The compounds with the general formulas II to X used as starting materials are partly known from the literature or can be prepared by methods known per se. Thus one achieves e.g. the compounds with the general formula II used as starting materials by acylation of the corresponding o-diami.no compounds resp. by reduction of the corresponding acylamino-nitro compounds, as well as the compounds with the general formulas III, IV, VI, VII or X by addition of a corresponding o-acylamino-amino compound (see BE-PS 810.545 and EP -A-0.024.290) and possibly subsequent debenzylation.

As mentioned at the outset, the new compounds of the general formula I, their 1H tautomers and their physiologically compatible acid addition salts exhibit long-lasting, superior pharmacological properties, in particular a blood pressure lowering, positive inotropic and/or antithrombotic effect.

As examples were the compounds

A = 2-[2'-methoxy-4'-(N-acetyl-sulfoximino-phenyl)]-5-cyano-beivzimidazole,

B = 2-(2'-methoxy-4<1->methylsulfinyl-phenyl)-5-acetyl-benzimidazole,

C = 2-(2'-methoxy-4<1->methylsulfonyl-phenyl)-5-acetyl-benzimidazole,

D = 5-cyano-2-(4<1->methanesulfonylamino-2<1->methoxy-phenyl)-benzimidazole and

E = 2-(2'-methoxy-4'-methoxycarbonylamino-phenyl)-imidazo-[4,5-c]pyridine

examined with regard to its biological properties as follows: 1. Determination of the blood pressure effect and positive inotropic effect on anesthetized cats

The investigations were carried out on cats anesthetized with pentobarbital sodium (40 mg/kg i.p.). The animals breathed spontaneously. The arterial blood pressure was measured in the Aorta abdominalis with a Statham pressure transducer (P 23 Dc). To determine the positive inotropic effect, the pressure in the left heart chamber was measured with a catheter tip manometer (Millar PC-350 A). On this basis, the contractility parameter ^P/^t^^g was found using an analog differentiator. The test compound was injected into a femoral vein. Polydiol 200 was used as solvent. Each compound was tested on at least 2 cats.

The following table contains the average values found:

2. Antithrombotic effect

Methodology

Platelet aggregation was measured by the method according to Born and Cross (J. Physiol. 170, 397 (1964) in platelet-rich plasma from healthy subjects. To inhibit coagulation, sodium citrate 3.14% was added to the blood in a volume ratio of 1:10.

Collagen-induced aggregation

The course of the reduction in the optical density in the platelet suspension was measured photometrically and recorded after the addition of the aggregation-triggering substance. On the basis of the angle of inclination of the density curve, the rate of aggregation is determined. The point on the curve where the greatest light penetration exists is used to calculate optical density.

Collagen - the amount is chosen as low as possible, but in such a way that an irreversibly continuous reaction curve is obtained. Commercial collagen from the company Hormonchemie, Munich, is used.

Before the collagen addition, the plasma is incubated in each case for 10 minutes with the test compound.

On the basis of the obtained measurement figures, an EC^q is graphically calculated, which represents a 50% change in the optical density as an expression of aggregation inhibition.

The following table contains the results obtained:

The new compounds are well compatible, and thus no cardiotoxic effects or circulatory damage could be observed when examining the compounds.

Due to their pharmacological properties, the compounds produced according to the invention and their physiologically compatible acid addition salts are suitable for the treatment of heart insufficiency of various origins, as they increase the contraction force of the heart and, by lowering blood pressure, facilitate the emptying of the heart, for the treatment and prevention of thromboembolic disorders such as coronary infarction, cerebral infarction, so-called transient ischemic attacks, Amaurosis fugax, for the prevention of arteriosclerosis and for metastasis prevention.

The dosage necessary to achieve an appropriate effect is suitably 0.3 to 4 mg/kg body weight, preferably 0.3 to 2 mg/kg body weight, 2-4 times a day.

For this purpose, the compounds produced according to the invention, possibly in combination with other active substances, together with one or more inert common carriers and/or diluents, e.g. with corn starch, milk sugar, cane sugar, micro-crystalline cellulose, magnesium stearate, polyvinylpyrrolidone, citric acid, tartaric acid, water, water/ethanol, water/glycerol, water/sorbitol, water/polyethylene glycol, propylene glycol, cetyl stearyl alcohol, carboxymethyl cellulose or fatty substances such as hard fat or suitable mixtures thereof, are incorporated into usual galenic preparations such as tablets, dragées, capsules, powders, suspensions or suppositories.

The following examples shall serve to further illustrate the invention.

Example 1

1(3)-methyl-2-(2'-methoxy-4'-methylmercapto-phenyl)-5-cyano-benzimidazole

1.0 g (0.003386 mol) of 2-(2'-methoxy-4'-methylmercapto-phenyl)-5-cyano-benzimidazole, dissolved in 15 ml of dimethylformamide, add 1.90 g (5 x 0.003386 mol ) potassium tert.-butylate and then, with stirring, 1.6 ml (5 x 0.003386 mol) of dimethyl sulfate. After 30

minute stirring is distributed 4 times between 20 ml of water and 20 ml of ethyl acetate each time. The combined ethyl acetate extracts

dry with 20 ml saturated sodium chloride solution over magnesium sulphate after shaking and evaporate to dryness. You get an oil that partially crystallizes.

Yield: 1.05 g (60% of the theoretical),

the thin-layer chromatogram (silica gel; methylene chloride/ethyl acetate = 1:1) shows an isomer at Rf= 0.45 and an isomer at R^= 0.40. By column chromatography on silica gel with methylene chloride/ethyl acetate, the isomer with R^= 0.45 is separated in pure form.

M.p.: 212-214°C.

Example 2

1(3)-methyl-2-(2'-methoxy-4'-methylsulfonyl-phenyl)-5-cyano-benzimidazole

Prepared by oxidation of 1(3)-methyl-2-(2'-methoxy-4'-methylmercapto-phenyl)-5-cyano-benzimidazole in formic acid with the 3-fold molar amount of hydrogen peroxide. White crystals are obtained in a yield of 80% of the theoretical, which melt in an interval from 194 to 220°C (isomer mixture).

Example 3

1(3)-methyl-2-(2'-methoxy-4'-methylsulfinyl-phenyl)-5-cyano-benzimidazole

485 mg (0.001568 mol) 1(3)-methyl-2-(2'-methoxy-4'-methylmercapto-phenyl)-5-cyano-benzimidazole is allowed to stand at room temperature for 65 hours in 5 ml of glacial acetic acid with 0 .12 ml of hydrogen peroxide (399 mg/ml;

corresponding to 0.9 x 0.001568 mol). You get white crystals. Melting range: 168-175°C (mixture of isomers).

Yield: 330 mg (64.7% of the theoretical).

Example 4

1(3)-methyl-2-(2<1->methoxy-4<1->methylsulfoximino-phenyl)-5-cyano-benzimidazole

1.048 g (0.00322 mol) of 1(3)-methyl-2-(2<1->methoxy-4'-methylsulfinyl-phenyl)-5-cyano-benzimidazole is dissolved in 7 ml of dimethylformamide together with 2.3 g (2.5 x 0.00 322 mol) O-mesitylenesulfonyl-acethydroxamic acid ethyl ester and 2.87 g (4.5 x 0.00322 mol) 4-toluenesulfonic acid hydrate under stirring and allowed to stand for 48 hours at room temperature. The mixture is made alkaline with 2N caustic soda while cooling and extracted exhaustively with a mixture of chloroform and ethanol = 9:1. After evaporating the solvent mixture, the mixture is chromatographed on a silica gel column with ethylene chloride/ethanol = 4:1. White crystals are obtained. Melting range: 207-218°C.

Yield: 0.450 g (41% of the theoretical).

Example 5

2-[2'-methoxy-4'-(N-methanesulfonyl-methylsulfoximino)-phenyl]-5-cyano- benzimidazole

Prepared from 2-(2'-methoxy-4'-methylsulfoximino-phenyl)-5-cyano-benzimidazole and methanesulfonyl chloride in pyridine.

M.p.: 270-273°C.

Yield: 62% of the theoretical.

Example 6

2-[2'-methoxy-4'-(N-acetyl-methylsulfoximino)-phenyl]-5-cyano-benzimidazole

Prepared from 2-(2'-methoxy-4<1->methylsulfoximino-phenyl)-5-cyano-benzimidazole and acetic anhydride.

M.p.: 212.5-214°C.

Yield: 89.6% of the theoretical.

Example 7

2-(2'-methoxy-4'-methylmercapto-phenyl)-5-trifluoromethyl-benzimidazole

5.0 g (0.02 mol) of 2-amino.no-4'-trifluoromethylaniline and 4.0 g (0.02 mol) of 2-methoxy-4-methylmercapto-benzoic acid are heated in 90 ml of phosphorus oxychloride for 2 hours until boiling . Excess phosphorus oxychloride is removed in vacuum on a rotary evaporator, the residue is added to ice water and neutralized with sodium bicarbonate.

The precipitated reaction product is suctioned off and recrystallized from ethanol.

M.p.: 144-147°C.

Yield: 4.78 g (70.4% of the theoretical).

Example 8

2-(2'-Methoxy-4<1->methylsulfinyl-phenyl)-5-trifluoromethyl-benzimidazole

Manufactured analogously to e.g. 3 from 2-(2<1->methoxy-4<1->methylmercapto-phenyl)-5-trifluoromethyl-benzimidazole and hydrogen peroxide. Melting point: 65°C (sintering),

decomp. at 120°C.

Yield: 99.1% of the theoretical.

Example 9

2-(2<1->methoxy-4<1->methylsulfonyl-phenyl)-5-trifluoromethyl-benzimidazole

Manufactured analogously to e.g. 2 from 2-(2'-methoxy-4<1->methylmercapto-phenyl)-5-trifluoromethyl-benzimidazole and hydrogen peroxide. M.p.: 217-220°C.

Yield: 84% of the theoretical.

Example 10

2-(2'-Methoxy-4'-methylsulfoximino-phenyl)-5-trifluoromethyl-benzimidazole

Manufactured analogously to e.g. 4 from 2-(2'-methoxy-4'-methylsulfinyl-phenyl)-5-trifluoromethyl-benzimidazole and O-mesitylenesulfonyl-acethydroxamic acid ethyl ester.

M.p.: 154°C.

Yield: 63% of the theoretical.

Example 11

2-(4'-methylmercapto-phenyl)-5-trifluoromethyl-benzimidazole

Manufactured analogously to e.g. 7 from 2-amino-4-trifluoromethyl-aniline and 4-methylmercapto-benzoic acid.

M.p.: 162-164°C.

Yield: 69% of the theoretical.

Example 12

2-(4'-methylsulfinyl-phenyl)-5-trifluoromethyl-benzimidazole

Manufactured analogously to e.g. 3 from 2-(4'-methylmercapto-phenyl)-5-trifluoromethyl-benzimidazole and hydrogen peroxide.

M.p.: 216-219°C.

Yield: 51% of the theoretical.

Example 13

2-(4'-methylsulfoximino-phenyl)-5-trifluoromethyl-benzimidazole

Manufactured analogously to e.g. 4 from 2-(4'-methylsulfinyl-phenyl)-5-trifluoromethyl-benzimidazole and O-mesitylenesulfonyl-acethydroxamic acid ethyl ester.

M.p.: 112-117°C.

Yield: 56% of the theoretical.

Example 14

2-(2'-Methoxy-4'-methylsulfinyl-phenyl)-5-methoxycarbonyl-benzimidazole

Manufactured analogously to e.g. 3 from 2-(2'-methoxy-4'-methylmercapto-phenyl)-5-methoxycarbonyl-benzimidazole and hydrogen peroxide. Melting point: 199-200°C.

Yield: 88% of the theoretical.

Example 15

2-(2 1 -Methoxy-4'-methylsulfonyl-phenyl)-5-methoxycarbonyl-benzimidazbl

Manufactured analogously to e.g. 2 from 2-(2'-methoxy-4'-methylmercapto-phenyl)-5-methoxycarbonyl-benzimidazole and hydrogen peroxide.

M.p.: 135°C.

Yield: 87% of the theoretical.

Example 16

2-(2'-Methoxy-4'-methylsulfoximino-phenyl)-5-methoxycarbonyl-benzimidazole

Manufactured analogously to e.g. 4 from 2-(2'-methoxy-4'-methylsulfinyl-phenyl)-5-methoxycarbonyl-benzimidazole and O-mesitylene-sulfonyl-acethydroxamic acid ethyl ester.

M.p.: 214-216°C.

Yield: 64% of the theoretical.

Example 17

2-(4'-methylmercapto-phenyl)-5-cyano-benzimidazole

Manufactured analogously to e.g. 7 from 3,4-diamino-benzonitrile and 4-methylmercapto-benzoic acid.

M.p.: 213-215°C.

Yield: 40% of the theoretical.

Example 18

2-(4'-methylsulfinyl-phenyl)-5-cyano-benzimidazole

Manufactured analogously to e.g. 3 from 2-(4'-methylmercapto-phenyl)-5-cyano-benzimidazole and hydrogen peroxide.

M.p.: 266-268°C.

Yield: 98% of the theoretical.

Example 19

2-(4'-methylsulfonyl-phenyl)-5-cyano-benzimidazole

Manufactured analogously to e.g. 2 from 2-(4<1->methylmercapto-phenyl)-5-cyano-benzimidazole and hydrogen peroxide.

M.p.: 271-273°C.

Yield: 55% of the theoretical.

Example 20

2-(4'-methylsulfoximino-phenyl)-5-cyano-benzimidazole

Manufactured analogously to e.g. 4 from 2-(4'-methylsulfinyl-phenyl)-5-cyano-benzimidazole and O-mesitylenesulfonyl-acethydroxamic acid ethyl ester.

M.p.: 272-274°C.

Yield: 78% of the theoretical.

Example 21

2-[2'-methoxy-4'-(N-3-carboxypropionyl-methylsulfoximino)]-5- cyano-benz imida zo1

Prepared from 2-(2'-methoxy-4'-methylsulfoximino-phenyl)-5-cyano-benzimidazole and succinic anhydride in boiling pyridine. M.p.: 265-268°C.

Yield: 92% of the theoretical.

Example 22

2-( 2'- methoxy- 5'- methylmercapto- phenyl)- 5- cyano- benzimidazole

a) 6.52 g of (2-methoxy-5-methylmercapto)-benz-(2-nitro-4-cyano)-anilide (prepared from 2-nitro-5-cyano-aniline and 2-methoxy-5-methylmercapto- benzoyl chloride) is suspended in 70 ml of ethanol, a solution of 16.5 sodium dithionite in 70 ml of water is added and heated on a steam bath for 30 minutes. After evaporation in a vacuum, the obtained residue is rubbed with a little water and suctioned off. The obtained 2-(2'-methoxy-5-methylmercapto-phenyl)-benz-(2-amino-4-cyano)-anilide is used in a moist state in the subsequent reaction. b) The product obtained under a) is heated in 15 ml of glacial acetic acid for 2 hours until boiling. The glacial acetic acid is distilled off in a vacuum and

distribute the residue between ethyl acetate and cold soda solution. The ethyl acetate phase is dried over magnesium sulphate and evaporated, whereby pale yellow crystals are obtained.

M.p.: 171-173°C.

Yield: 3.04 g (54% of theoretical).

Example 23

2-(2'- methoxy- 51- methylsulfinyl- phenyl)- 5- cyano- benzimidazole

Manufactured analogously to e.g. 3 from 2-(2'-methoxy-5<1->methyl-markapto-phenyl)-5-cyano-benzimidazole and hydrogen peroxide.

M.p.: 215-217°C.

Yield: 75% of the theoretical.

Example 24

2-( 2'- methoxy- 5'- methylsulfonyl- phenyl)- 5- cyano- benzimidazole

Manufactured analogously to e.g. 2 from 2-(2<1->methoxy-5<1->methylmercapto-phenyl)-5-cyano-benzimidazole and hydrogen peroxide.

M.p.: 276-278°C.

Yield: 88% of the theoretical.

Example 25

2-( 2'- methoxy- 5'- methylsulfoximino- phenyl)- 5- cyano- benzimidazole

Manufactured analogously to e.g. 4 from 2-(2<1->methoxy-5<1->methylsulfinyl-phenyl)-5-cyano-benzimidazole and O-mesitylenesulfonyl-acethydroxamic acid ethyl ester.

M.p.: 284-285°C.

Yield: 84% of the theoretical.

Example 26

2-( 2'- methoxy- 4'- ethyl mercapto- phenyl)- 5- cyano- benzimidazole

Manufactured analogously to e.g. 22 from 2-(2'-methoxy-4'-ethylmercapto)-benz-(2-nitro-4-cyano)-anilide by reduction with sodium dithionite and subsequent ring closure.

M.p.: 161-163°C.

Yield: 85% of the theoretical.

Example 27

2-( 2'- methoxy- 4'- ethylsulfinyl- phenyl)- 5- cyano- benzimidazole

Manufactured analogously to e.g. 3 from 2-(2'-methoxy-4'-ethylmercapto-phenyl)-5-cyano-benzimidazole and hydrogen peroxide.

M.p.: 234-236°C.

Yield: 98% of the theoretical.

Example 28

2-( 2'- methoxy- 4'- ethylsulfonyl- phenyl)- 5- cyano- benzimidazole

Manufactured analogously to e.g. 2 from 2-(2'-methoxy-4'-ethyl-markapto-phenyl)-5-cyano-benzimidazole and hydrogen peroxide.

M.p.: 208-209°C.

Yield: 85% of the theoretical.

Example 29

2-( 2'- methoxy- 4'- ethylsulfoximino- phenyl)- 5- cyano- benzimidazole

Manufactured analogously to e.g. 4 from 2-(2'-methoxy-4'-ethylsulfinyl-phenyl)-5-cyano-benzimidazole and O-mesitylenesulfonyl-acethydroxamic acid ethyl ester.

M.p.: 252-254°C.

Yield: 85% of the theoretical.

Example 30

2-[ 2'-( 2- methylmercapto- ethoxy)- naphthyl- 3-]- 5- cyano- benzimidazole

Manufactured analogously to e.g. 7 from 2-amino-4-cyanoaniline and 2-(2-methylmercapto-ethoxy)-3-naphthoic acid by boiling in phosphorus oxychloride.

M.p.: 186-188°C.

Yield: 65% of the theoretical.

Example 31

2-[ 2'-( 2- methylsulfinyl- ethoxy)- naphthyl- 3]- 5- cyano- benzimidazole

Manufactured analogously to e.g. 3 from 2-[2<1->(2-methylmercaptoethoxy)-naphthyl-3]-5-cyano-benzimidazole and hydrogen peroxide.

M.p.: 207-208°C.

Yield: 58% of the theoretical.

Example 32

2-[ 2-( 2- methylsulfonyl- ethoxy)- naphthyl- 3-]- 5- cyano- benzimidazole

Manufactured analogously to e.g. 2 from 2-[2'-(2-methylmercaptoethoxy)-naphthyl-3-]-5-cyano-benzimidazole and hydrogen peroxide. M.p.: 257-259°C.

Yield: 72% of the theoretical.

Example 33

2-[21-(2-methylsulfoximino-ethoxy)-naphthyl-3]-5-cyano-benzimidazole

Manufactured analogously to e.g. 4 from 2-[2'-(2-methylsulfinylethoxy)-naphthyl-3]-5-cyano-benzimidazole and O-mesitylenesulfonyl-acethydroxamic acid ethyl ester.

M.p.: 192-194°C.

Yield: 52% of the theoretical.

Example 34

2-( 2'- methoxy- 4'- amidosulfonyl- phenyl)- 5- acetyl- benzimidazole

a) 16 g of 2-methoxy-4-amidosulfonyl-benzoic acid are heated with 80 ml of thionyl chloride and 10 ml of dimethylformamide in 150 ml of absolute

toluene for 30 minutes to boiling and then evaporated to dryness in vacuo. The obtained crude, crystalline 2-methoxy-4-(dimethyl-amino-formimido-sulfonyl)-benzoyl chloride is used immediately for the subsequent reaction.

Yield: 21.5 g (100% of the theoretical).

b) 17.2 g of 2-methoxy-4-(dimethylamino-formimido-sulfonyl)-benzoyl chloride is heated with 12.4 g of 3-nitro-4-amino-acetophenone

in 150 ml of absolute toluene for 2 hours until boiling. Below this, the initially clear solution becomes cloudy due to crystallized 2-methoxy-4-(dimethylamino-formimido-sulfonyl)-benz-(2-nitro-4-acetyl)-anilide, which is filtered off after cooling, washed with a little methyl ethyl ketone and dried.

Melting point: 230-235°C.

Yield: 20.8 g (77% of the theoretical).

c) 19 g of 2-methoxy-4-(dimethylamino-formimido-sulfonyl)-benz-(2-nitro-4-acetyl)-anilide are heated with 50.5 g of sodium dithionite

in a mixture of 190 ml of ethanol and 200 ml of water for 2.5 hours until boiling. Evaporate to dryness and partition between methylene chloride and water. Evaporation of the organic phase after drying over magnesium sulfate gives 2-methoxy-4-(dimethylamino-formimido-sulfonyl)-benz-(2-amino-4-acetyl)-anilide, which is used in crude form in the subsequent reaction.

Yield: 5.3 g (30% of the theoretical).

d) 0.400 g of 2-methoxy-4-(dimethylamino-formimido-sulfonyl)-benz-(2-amino-4-acetyl)-anilide is heated in 10 ml of 5N hydrochloric acid for 1 hour until boiling. The crystallized 2-(2<1->methoxy-4<1->amidosulfonyl-phenyl)-5-acetyl-benzimidazole is filtered off after cooling, washed acid-free and dried.

M.p.: 269-272°C.

Yield 280 mg (85% of the theoretical).

Example 35

2-( 2'- methoxy- 4'- methylmercapto- phenyl)- 5- acetyl- benzimidazole

a) Analogous to e.g. 34b) 2-methoxy-4-methylmercapto-benzoyl chloride and 3-nitro-4-amino-acetophenone are converted to (2-methoxy-4-methylmercapto)-benz-(2-nitro-4-acetyl)-anilide , and this b) is reduced with sodium dithionite to (2-methoxy-4-methylmercapto)-benz-(2-amino-4-acetyl)-anilide analogously to ex. 34c),

as then

c) analogous to e.g. 34d) is reacted with boiling hydrochloric acid to 2-(2<1->methoxy-4'-methylmercapto-phenyl)-5-acetyl-benzimidazole.

M.p.: 154-157°C.

Yield: 63% of the theoretical.

Example 36

2-( 2'- methoxy- 4'- methylsulfinyl- phenyl)- 5- acetyl- benzimidazole

Manufactured analogously to e.g. 3 from 2-(2'-methoxy-4'-methylmercapto-phenyl)-5-acetyl-benzimidazole and hydrogen peroxide. M.p.: 184-187°C.

Yield: 59% of the theoretical.

Example 37

2-( 2'- methoxy- 4'- methylsulfonyl- phenyl)- 5- acetyl- benzimidazole

Manufactured analogously to e.g. 2 from 2-(2<1->methoxy-4'-methylmercapto-phenyl)-5-acetyl-benzimidazole and hydrogen peroxide. M.p.: 203-205°C.

Yield: 78% of the theoretical.

Example. 38

2-(2'-Methoxy-5-methylsulfoximino-phenyl)-1H-imidazo[4,5-b]-pyridine

Manufactured analogously to e.g. 4 from 2-(2'-methoxy-5<1->methylsulfinyl-phenyl)-1H-imidazo[4,5-b]pyridine and O-mesitylenesulfonyl-acethydroxamic acid ethyl ester.

M.p.: 26 3.5°C.

Yield: 83% of the theoretical.

Example 39

2-(2<1->ethoxy-5'-methylsulfoximino-phenyl)-1H-imidazo[4,5-b]-pyridine

Manufactured analogously to e.g. 4 from 2-(2'-ethoxy-5<1->methylsulfinyl-phenyl)-1H-imidazo[4,5-b]pyridine and O-mesitylenesulfonyl-acethydroxamic acid ethyl ester.

M.p.: 277°C.

Yield: 6 2% of the theoretical.

Example 40

2-(2'-ethoxy-41-methylsulfoximino-phenyl)-1H-imidazo[4,5-b]-pyridine

Manufactured analogously to e.g. 4 from 2-(2<1->ethoxy-4'-methylsulfinyl-phenyl)-1H-imidazo[4,5-b]pyridine and O-mesitylenesulfonyl-acethydroxamic acid ethyl ester.

M.p.: 176-178°C.

Yield: 80% of the theoretical.

Example 41

2-(2,-ethoxy-4'-n-propylsulfoximino-phenyl)-1H-imidazo-[4,5-b]-pyridine

Manufactured analogously to e.g. 4 from 2-(2<1->ethoxy-4'-n-propylsulfinyl-phenyl)-1H-imidazo[4,5-b]-pyridine and O-mesitylene-

sulfonyl-acethydroxamic acid ethyl ester.

M.p.: 135-137°C.

Yield: 71% of the theoretical.

Example 4 2

2-(2<1->methoxy-4'-methylsulfoximino-phenyl)-6-methyl-imidazo-[4,5-b]-pyridine

Manufactured analogously to e.g. 4 from 2-(2'-methoxy-4'-methylsulfinyl-phenyl)-6-methyl-1H-imidazo[4,5-b]pyridine and O-mesitylenesulfonyl-acethydroxamic acid ethyl ester.

M.p.: 233°C.

Yield: 58% of the theoretical.

Example 4 3

2-(2(2-methylsulfoximino-ethoxy)-4'-methoxy-phenyl]-1H-imidazo [45-b] pyridine-mesitylenesulfonate 14 g of O-mesitylenesulfonyl-acethydroxamic acid ethyl ester, dissolved in 20 ml of dioxane is added dropwise at 22-24°C 10 ml of 90% sulfuric acid under slight external cooling. Stir for 20 min. and then pour the mixture onto 300 ml of ice and shake off the free O-mesitylenesulfonyl-hydroxylamine with methylene chloride and dry the solution over sodium sulfate. To this solution, 6.62 g of 2-[2'-(2-methylsulfinyl-ethoxy)-4'-methoxy-phenyl]-1H-imidazo[4,5-b]pyridine are added. After about 5 minutes, crystals begin to separate , and the mixture is stirred overnight.The crystalline precipitate is filtered off with suction and recrystallized from ethanol.

M.p.: 163°C.

Yield: 42% of the theoretical.

Example 4 4

2-(2<1->methoxy-4<1->methylsulfoximino-phenyl)-6-chloro-1H-imidazo[4,5-b]pyridine

0.453 g of 2-(2'-methoxy-4'-methylsulfinyl-phenyl)-6-chloro-1H-imidazo[4,5-b]pyridine is stirred at 50°C into 9 g of polyphosphoric acid and then 0.5 g is added in portions sodium azide. After standing overnight, stir with ice and adjust the pH to 7.5 with 40% caustic soda. The thereby precipitated crystals are suctioned off and recrystallized from ethanol.

M.p.: 282°C.

Yield: 0.284 g (60% of theoretical).

Example 4 5

2-(2'-Methoxy-4'-methylsulfoximino-phenyl)-1H-imidazo-[4,5-b]pyridine: Prepared analogously to ex. 4 4 from 2-(2'-methoxy-4'-methylsulfinyl-phenyl)-1H-imidazo[4,5-b]pyridine and sodium azide.

M.p.: 236-237°C.

Yield: 86% of the theoretical.

Example 46

2-(2'-Methoxy-4'-methylsulfoximino-phenyl)-1H-imidazo-[4,5-c]pyridine

Manufactured analogously to e.g. 44 from 2-(2'methoxy-4'-methylsulfinyl-phenyl)-1H-imidazo[4,5-c]pyridine and sodium azide.

M.p.: 253-257°C.

Yield: 62% of the theoretical.

Example 47

8-( 2' methoxy- 4'- methylsulfoximino- phenyl- phenyl)- purine

Manufactured analogously to e.g. 44 from 8-(2'-methoxy-4'-methylsulfinyl-phenyl)-purine and sodium azide.

M.p.: 261°C (decomp.)

Yield: 66% of the theoretical.

Example 48

8-(2'-Methoxy-4'-methylsulfoximino-phenyl)-theophylline mesitylene sulfonate

Manufactured analogously to e.g. 4 3 from 8-(2'-methoxy-4'-methylsulfinyl-phenyl)-theophylline and O-mesitylenesulfonyl-hydroxylamine. M.p.: 238°C.

Yield: 32% of the theoretical.

Example 49

2-( 2'- methoxy- 4'- benzyloxy- phenyl)- 5- methyl mercapto- benzimidazole

a) Produced analogously to e.g. 34b from 2-methoxy-4-benzyloxy-benzoyl chloride and 2-nitro-4-methylmercapto-aniline, b) the obtained 2-methoxy-4-benzyloxy)benz-(2-nitro-4-methylmercapto)-anilide is reduced analogously with e.g. 34c with sodium dithionite, c) and the thus obtained 2-methoxy-4-benzyloxy)-benz-(2-amino-4-methylmercapto)-anilide are cyclized analogously to ex. 34d with boiling hydrochloric acid.

M.p.: 238-240°C.

Yield: 81% of the theoretical.

Example 50

2-(2'-methoxy-4'-benzyloxy-phenyl)-5-methylsulfonyl- benzimidazole

Manufactured analogously to e.g. 2 from 2-(2<1->methoxy-4<1->benzyloxy-phenyl)-5-methylmercapto-benzimidazole and hydrogen peroxide. Yield: 92% of the theoretical.

M.p.: 156-159°C.

Example 51

2-( 2'- methoxy- 4'- hydroxy- phenyl)- 5- methylsulfonyl- benzimidazole

Prepared from 2-(2'-methoxy-5-benzyloxy-phenyl)-5-methylsulfonyl-benzimidazole by catalytic hydrogenation with hydrogen at room temperature in dimethylformamide.

Yield: 60% of the theoretical.

Melting point: 255-260°C.

Example 52

2-(2<1->methoxy-4<1->methanesulfonyloxy-phenyl)-5-methylsulfonyl-benzimidazole

Prepared from 2-(2'-methoxy-4<1->hydroxy-phenyl)5-methylsulfonyl-benzimidazole and methanesulfonyl chloride in pyridine. Yield: 68% of the theoretical.

M.p.: 125-129°C.

Example 53

5- cyano- 2-( 2'- methoxy- 4'- methanesulfonylamino- phenyl)- benzimidazole

Prepared from 2-methoxy-4-methanesulfonylamino-benzoic acid and 3,4-diamino-benzonitrile analogously to ex. 7.

Yield: 17.5% of the theoretical.

M.p.: 293-295°C.

Example 54

2-(2'-Methoxy-4'-methanesulfonylamino-phenyl)-imidazo-[4,5-b]-naphthalene hydrate

Prepared from 2-methoxy-4-methanesulfonylamino-benzoic acid and 2,3-diamino-naphthalene analogously to ex. 7.

Yield: 42% of the theoretical.

Melting point: amorphous, from approx. 100°C.

Example 55

5-aminosulfonyl-2-(2'-methoxy-4'-methylmercapto-phenyl)-benzimidazole

Prepared from 2-methoxy-4-methylmercapto-benzoic acid and 4-aminosulfonyl-1,2-diamino-benzene analogously to ex. 7. Yield: 18.9% of the theoretical.

M.p.: 274-276°C.

Example 56

5-acetyl-2-(2<1->methoxy-4'-methanesulfonylamino-phenyl)-benzimidazole

Prepared from 2-methoxy-4-methanesulfonylamino-benzoic acid and 3,4-diamino-acetophenone analogously to ex. 7. Yield: 79% of the theoretical.

M.p.: 141-143°C.

Example 57

5-benzoyl-2-(2'-methoxy-4'-methanesulfonylamino-phenyl)-benzimidazole

Prepared from 2-methoxy-4-methanesulfonylamino-benzoic acid and 3,4-diamino-benzophenone analogously to ex. 7. Yield: 62% of the theoretical.

M.p.: 139-141°C.

Example 58

2- amino- 8-(<2>'- me<t>oxy- 4'- methylmerca<p>to- phenyl)- purine

Prepared from 2-methoxy-4-methylmercapto-benzoic acid and 2,4,5-triamino-pyrimidine analogously to ex. 7. Yield: 17% of the theoretical.

M.p.: 212-214°C.

Example 59

6-cyano-2-(2<1->methoxy-4'-methylmercapto-phenyl)-imidazo-[4,5-b]pyridine

Prepared from 2-methoxy-4-methylmercapto-benzoic acid and 5-cyano-2,3-diami.no-pyridine analogously to ex. 7. Yield: 28% of the theoretical.

M.p.: 268-270°C.

Example 6 0

5-aminosulfonyl-2-(2'-methoxy-41-methylsulfonyl-phenyl)-benzimidazole

Prepared from 5-aminosulfonyl-2-(2'-methoxy-4'-methylmercapto-phenyl)-benzimidazole and hydrogen peroxide analogously to ex. 2.

Yield: 38.3% of the theoretical.

Melting point: 298-300°C.

Example 61

2-amino-8-(2'-methoxy-4'-methylsulfinyl-phenyl)-purine Prepared from 2-amino-8-(2'-methoxy-4'-methylmercapto-phenyl)-purine and hydrogen peroxide analogously to ex. 3. Yield: 5 3% of the theoretical.

Melting point: amorphous, from approx. 150°C.

Example 62 2-(2<1->methoxy-4'-methoxycarbonylamino-phenyl)-imidazo-[4,5-c]pyridine a) 3.27 g (30 mmol) of 3,4-diamino-pyridine and 5, 02 g (30 mmol) of 4-amino-2-methoxy-benzoic acid is heated for 2 hours with vigorous stirring to 130°C in 50 g of polyphosphoric acid. After cooling, add approx. 100 ml of water, the precipitated yellow precipitate is filtered off, suspended in 50 ml of water and made weakly alkaline with concentrated ammonia. The undissolved product is extracted and dried in an air circulation drying cabinet at 50°C. 6.8 g of 2-(4'-amino-2<1->methoxy-phenyl)-imidazo[4,5-c]pyridine is obtained, which is not purified further, but reacted directly further. b) 1.2 g (5 mmol) of 2-(4'-amino.no-2'-methoxy-phenyl)-imidazo-[4,5-c]pyridine, dissolved in 20 ml of pyridine, add 0, 7 ml of chloroformic acid methyl ester at -10°C. It is then slowly warmed to room temperature and stirred for a further 2 hours. The reaction mixture is then evaporated to dryness, the residue is stirred for 1 hour in 30 ml of 5% sodium bicarbonate solution, filtered off with suction, dried and purified by column chromatography over silica gel (eluent: methylene chloride with 1-12% ethanol).

Yield: 67% of that theoretical.

M.p.: 229-230°C.

Example 6 3

5-ethylaminocarbonylamino-2-(2'methoxy-4'-methanesulfonyloxy-phenyl)- benzimidazole

1.0 g (3 mmol) of 5-amino-2-(4'-methanesulfonyloxy-2'-methoxy-phenyl)-benzimidazole is dissolved in 30 ml of tetrahydrofuran, 2.5 ml of ethyl isocyanate is added and heated to reflux temperature. After 15 minutes, the solvent and excess ethyl isocyanate are evaporated in vacuo. The obtained residue is chromatographed over 250 g of aluminum oxide (neutral) (eluent: methylene chloride with 4% ethanol).

Yield: 2 7.5% of the theoretical.

M.p.: 194-196°C.

Example 64

5-isopropylaminocarbonylamino-2-(2'-methoxy-4'-methanesulfonyloxy-phenyl)-benzimidazole

Prepared from 5-amino-2-(2'-methoxy-4<1->methanesulfonyloxy-phenyl)-benzimidazole and isopropylisocyanate analogous to ex. 63. Yield: 27.1% of the theoretical.

M.p.: 189-190°C.

Example 65

8-(2'-Methoxy-4'-methylaminocarbonylamino-phenyl)-purine Prepared from 8-(4'-amino-2'-methoxy-phenyl)-purine and methyl isocyanate analogous to ex. 63.

Yield: 17.3% of the theoretical.

M.p.: 269-271°C.

Example 66

' 4- cyano- 2-( 4'- methanesulfonyloxy- 2'- methoxy- phenyl)- benzimidazole

3.0 g (11.3 mmol) of 4-cyano-2-(4'-hydroxy-2'-methoxy-phenyl)-benzimidazole, dissolved in 90 ml of 1N caustic soda, is added dropwise to 5 ml of methanesulfonyl chloride while stirring. By gradual addition

of further IN caustic soda, the pH value in the reaction solution is kept at 10.0 to 10.5. The precipitated product is then filtered off, washed with water, dried and purified by column chromatography. over 300 g aluminum oxide (neutral, activity level II)

(eluent: methylene chloride).

Yield: 72% of the theoretical.

M.p.: 225-227°C.

Example 6 7 4-aminocarbonyl-2-(4'-methanesulfonyloxy-2'-methoxy-phenyl)-benzimidazole 1.0 g (2.9 mmol) 4-cyano-2-(4'-methanesulfonyloxy-2'-methoxy -phenyl)-benzimidazole is stirred in 20 ml of concentrated sulfuric acid for 18 hours at room temperature, the solution is then poured onto 50 g of ice and neutralized with concentrated ammonia under ice-cooling. The precipitated product is filtered off, dried and purified by column chromatography over silica gel (eluent: methylene chloride with 5% ethanol).

Yield: 79% of the theoretical.

Melting point: from 250°C (sinters).

Example 68

5-methylaminocarbonylmethylamino-2-(4 1-methanesulfonyloxy-2'- methoxy-phenyl)- benzimidazole

Prepared from 5-methylaminocarbonylmethylamino-2-(4 1-hydroxy-2'-methoxy-phenyl)-benzimidazole and methanesulfonyl chloride analogously to ex. 66.

Yield: 6 3% of the theoretical.

M.p.: 210-212°C.

Example 69

4-methyl-2-(4'-methanesulfonyloxy-2<1->methoxy-phenyl)-benzimidazole

Prepared from 4-methyl-2-(4'-hydroxy-2'-methoxy-phenyl)-benzimidazole and methanesulfonyl chloride analogously to ex. 66. Yield: 6 0% of the theoretical.

M.p.: 195-196°C.

Example 70

2-amino-8-(4'-methanesulfonyloxy-2'-methoxy-phenyl)-purine Prepared from 2-amino-8-(4 1-methanesulfonyloxy-2 1-methoxy-phenyl)-purine and methanesulfonyl chloride analogously to e.g. 66. Yield: 41% of the theoretical.

M.p.: 246-247°C.

Example 71

4-Methoxycarbonyl-2-(4'-methanesulfonyloxy-2<1->methoxy-phenyl)-benzimidazole

A solution of 400 mg (1/34 mmol/ 4-methoxycarbonyl-2-(4'-hydroxy-2'-methoxy-phenyl)-benzimidazole, 10 ml of pyridine and 0.8 ml of methanesulfonyl chloride is stirred for 18 hours at room temperature, evaporated then in vacuum, and the residue is stirred with 15 ml of water and adjusted to pH 8 with 0.5N hydrochloric acid. The solution thus obtained is extracted three times with 10 ml of methylene chloride each time, the extracts are dried and evaporated. The solid residue is purified by column chromatography over 150 g silica gel (eluent: methylene chloride with 1% ethanol).

Yield: 79.5% of the theoretical.

M.p.: 182-183°C.

Example 72

2-(4'-methanesulfonyloxy-2'-methoxy-phenyl)-imidazo[4,5-b]-naphthalene

Prepared from 2-(4<1->hydroxy-2'-methoxy-phenyl)-imidazo-[4,5-b]naphthalene and methanesulfonyl chloride analogously to ex. 71. Yield: 9% of the theoretical.

M.p.: 195-197°C.

Example 73

5-acetaminomethyl-2-(2'-methoxy-4'-methanesulfonyloxy-phenyl)-benzimidazole

Prepared from 5-acetaminoethyl-2-(4<1->hydroxy-2'-methoxy-phenyl)-benzimidazole and methanesulfonyl chloride analogously to ex. 71. Yield: 17.3% of the theoretical.

Example 74

5-acetyl-2-(4<1->methanesulfonyloxy-2'-methoxy-phenyl)-benzimidazole

Prepared from 5-acetyl-2-(4<1->hydroxy-2<1->methoxy-phenyl)-benzimidazole and methanesulfonyl chloride analogously to ex. 71. Yield: 44% of the theoretical.

M.p.: 182-184°C.

Example 75

5-(phenyl-methoxymethyl)-2-(4'-methanesulfonyloxy-2'-methoxy-phenyl)- benzimidazoT

Prepared from 5-(phenyl-methoxymethyl-2-(4<1->hydroxy-2<1->methoxy-phenyl)-benzimidazole and methanesulfonyl chloride analogously to ex. 71.

Yield: 8% of the theoretical..

M.p.: amorphous.

Claims (3)

1. Analogous method for the preparation of therapeutically active 2-arylimidazoles of the general formula where R means a hydrogen atom or an alkyl group, Ar means a group with the formula A and B together with the two intervening carbon atoms mean a group with the formula where R^ is an alkylsulfonyl, alkylsulfonyl, alkylsulfonyl or alkylsulfoximino group, an alkylsulfoximino group substituted on the nitrogen atom with an alkanoyl, alkylsulfonyl or hydroxycarbonylalkylenecarbonyl group, an ethoxy or n-propoxy group each of which is substituted in the terminal position with an alkylsulfenyl-, alkylsulfinyl, alkylsulfonyl or alkylsulfoximino group, an alkoxycarbonylamino- or N-alkylaminocarbonyl-amino group or also in the 4-position a hydroxy-, phenylalkoxy-, amino-sulfonyl-, alkylsulfonyloxy- or alkylsulfonylamino group, when a) A and B together with the two intervening carbon atoms mean a b) R. means an alkyl-, alkanoyl-, N-alkanoylaminomethyl-, benzoyl-, phenyl-methoxymethyl-, aminosulfonyl-, N-ethylaminocarbonyl-amino-, N-n-propylaminocarbonyl-amino-, N-isopropylaminocarbonyl- ami.no- or N-alkyl-N-alkylaminocarbonyl-amino group, or c) Rg means an amino group, where at least one of the residues must have the meanings specified under a), b) and c), R2 means a hydrogen atom or an alkoxy group, R^ means an ethoxy or n-propoxy group, each of which is substituted in the terminal position with an alkylsulfenyl-, alkylsulfinyl-, alkylsulfonyl or alkylsulfoximino group, R4 means an alkyl-, alkoxycarbonyl-, alkanoyl-, N-alkanoyl-aminomethyl-, benzoyl-, phenyl-methoxymethyl-, aminocarbonyl-, cyano-, trifluoromethyl-, aminosulfonyl-, N-alkylaminocarbonyl-amino- or N-alkyl- N-alkylaminocarbonylamino group, R- means a hydrogen or halogen atom, an alkyl or cyano group, and Rg means a hydrogen atom or an amino group, provided that a) R^ does not mean an alkyl mercapto group in the 4-position when Rg means a hydrogen atom or R^ in the 5-position a methoxycarbonyl, aminocarbonyl or cyano group and at the same time R2 in the 2-position a methoxy or ethoxy group and R a hydrogen atom, b) R^ does not mean an alkylsulfinyl group in the 4-position when Rg means a hydrogen atom or R^ in the 5-position a cyano or aminocarbonyl group and at the same time R2 in the 2-position a methoxy or ethoxy group and R a hydrogen atom, c) R^ does not mean an alkylsulfonyl group in the 4-position when Rg means a hydrogen atom or R4 in the 5-position a cyano or amino carbonyl group and at the same time in the 2-position a methoxy or ethoxy group and R a hydrogen atom, d) R^ does not mean an alkylsulfoximino group in the 4-position when R^ in the 5-position means a cyano or carbamido group and at the same time R2 in the 2-position a methoxy or ethoxy group and R a hydrogen atom, or e) R^ in the 4-position does not mean a hydroxy or phenylalkoxy group when Rg means a hydrogen atom or R^ in the 5-position a methoxycarbonyl, aminocarbonyl or cyano group and at the same time 1*2 in the 2-position a methoxy or ethoxy group and R a hydrogen atom, the above-mentioned alkyl, alkylene, alkoxy and alkanoyl parts in each case may contain 1-3 carbon atoms, as well as the compounds 5-cyano-2-(4'-methanesulfonylamino-2'-methoxy-phenyl)-benzimidazole, 4-methyl-2-(4 <1-> methanesulfonyloxy-2'-methoxy-phenyl)-benzimidazole, 4-cyano-2-(4 <1-> methanesulfonyloxy-2'-methoxy-phenyl)-benzimidazole, 4-aminocarbonyl-2-(4'-methanesulfonyloxy-2 <1-> methoxy-phenyl)-benzimidazole and 4-methoxycarbonyl-2-(4 <1-> methanesulfonyloxy-2'-methoxy-phenyl)-benzimidazole, their tautomers when R represents a hydrogen atom, and their acid addition salts, characterized in that a) a compound possibly produced in the react ion mixture with the general formula where A, B and R are as indicated above, one of the residues X and Y means a hydrogen atom and the other of the residues X and Y or both residues X and Y means a group of the formula Scar is as stated above, and Z 2 , which may be the same or different, mean optionally substituted amino groups or optionally substituted with lower alkyl groups hydroxy or marcapto groups, or Z <->^ and Z 2 together mean an oxygen or sulfur atom, one optionally with an alkyl group with 1 -3 carbon atoms substituted imino group, an alkylenedioxy or alkylenedithio group with each 2 or 3 carbon atoms, ring closure, or b) for the preparation of compounds of the general formula I where means an alkylsulfonyl, alkylsulfonyl or alkylsulfoximino group, an alkylsulfoximino group substituted on the nitrogen atom with an alkanoyl, alkylsulfonyl or hydroxycarbonyl-1-alkylenecarbonyl group, an ethoxy or n-propoxy group as in the end position is substituted with an alkylsulfinyl, alkylsulfonyl or alkylsulfoximino group, or R- is an ethoxy or n-propoxy group which is substituted in the terminal position with an alkylsulfinyl, alkylsulfonyl or alkylsulfoximino- group, a compound with the general formula is oxidized where A, B and R are as indicated above, and Ar^ has the meanings indicated for Ar above, however R^ must be an alkylsulfenyl, alkylsulfinyl or alkylsulfimino group, one on the nitrogen atom with an alkanoyl, alkylsulfonyl or hydroxycarbonyl-alkylenecarbonyl group substituted alkylsulfimino group, an ethoxy or n-propoxy group which is substituted in the terminal position with an alkylsulfenyl, alkylsulfinyl or alkylsulfimino group, or R~ is an ethoxy or n-propoxy group which is substituted in the terminal position with an alkylsulfenyl, alkylsulfinyl or alkylsulfimino group, or c) for the preparation of compounds of the general formula I where R^ means an alkylsulfoximino group, an ethoxy or n-propoxy group, which is substituted in the terminal position with an alkylsulfoximino group, or R^ is an ethoxy or n-propoxy group, which is substituted in the terminal position with an alkylsulfoximino group, a sulfoxide with the general formula is reacted where A, B and R are as indicated above, and Ar2 has the meanings indicated for Ar above, with R^ however meaning an alkylsulfinyl group, an ethoxy or n-propoxy group, which is substituted in the terminal position with an alkylsulfinyl group, or R~ means a ethoxy- or n-propoxy group, which is substituted in the terminal position with an alkylsulfinyl group, optionally with hydrogen azide formed in the reaction mixture, ord) for the preparation of compounds of the general formula I, where R^ means an alkylsulfoximino group, an ethoxy- or n -propoxy group which is substituted in the terminal position with an alkylsulfoximino group, or R^ means an ethoxy or n-propoxy group, which is substituted in the terminal position with an alkylsulfoximino group, a sulfoxide is reacted with the general formula where A, B and R are as indicated above, and Ar- has the meanings given for Ar above, with R^ meaning an alkylsulfinyl group, an ethoxy or n-propoxy group which is substituted in the terminal position with an alkylsulfinyl group, or R_ means a ethoxy or n-propoxy group, which is substituted in the terminal position with an alkylsulfinyl group, with a compound of the general formula optionally produced in the reaction mixture where U means a carbonyl or sulfonyl group, and R7 means an aryl group disubstituted in the o-position such as a 2,4,6-trimethylphenyl or 2,4,6-triisopropylphenyl group, or e) for the preparation of a compound of the general formula I, where means a on the nitrogen atom with an alkanoyl, alkylsulfonyl or hydroxycarbonylalkylenecarbonyl group substituted with an alkylsulfoximino group, a compound of the general formula is acylated where A, B and R are as indicated above, and Ar~ has the meaning given for Ar above, whereby however R^ means an alkylsulfoximino group, with a compound of the general formula where Rg means an alkanoyl, alkylsulfonyl or hydroxycarbonyl-alkylenecarbonyl group, and V means a nucleofuge leaving group such as a halogen atom or an alkanoyloxy group, or esters thereof with anhydrides, or f) for the preparation of compounds of the general formula I where R1 means an alkylsulfonyloxy, alkylsulfonylamino, alkoxycarbonylamino or N-alkylaminocarbonylamino group or R^ an alkanoylaminomethyl-, N-ethylaminocarbonylamino-, N-n-propylaminocarbonylamino-, N-isopropylaminocarbonylamino- or N-alkyl-N-alkylaminocarbonylamino group, a compound of the general formula is acylated where A, B and R are as indicated above, and Ar^ has the meanings indicated for Ar above, with however R 1 meaning a hydroxy or amino group or R^ an aminomethyl or amino group, with a compound of the general formula where Rn means an alkyl group with 1-3 carbon atoms and W an O=N=C- or halosulfonyl group such as a chloro or bromosulfonyl group, or Rg means a methyl or ethyl group and W a -CO-V group, where V is a nucleofuge leaving group such as a halogen atom or an alkanoyloxy group, or g) for the preparation of compounds of the general formula I where R means an alkyl group, a compound of the general formula is alkylated where A, B and Ar are as above indicated, and optionally, a thus prepared compound of the general formula I where R 4 means a benzyloxy group is transferred by debenzylation to the corresponding hydroxy compound, and/or a thus prepared compound of the general formula I where R 4 means a cyano group is transferred by hydrolysis to the corresponding aminocarbonyl compound , and or a prepared compound of the general formula I is transferred to its acid addition salt, in particular to its physiologically compatible acid addition salt with an inorganic or organic acid. 2. Method according to claim 1, characterized in that one produces: 2-[2'methoxy-4'-(N-acetyl-methylsulfoximino-phenyl)]-5-cyano-benzimidazole, 2-(2'-Methoxy-4'-methylsulfonyl-phenyl)-5-acetyl-benzimidazole, 2-(2'-Methoxy-4'-methylsulfonyl-phenyl)-5-acetyl-benzimidazole, 5- cyano-2-(4'-methanesulfonylamino-2'-methoxyphenyl)-benzimidazole, 2-(2'-methoxy-4'-methoxycarbonylamino-phenyl)-imidazo[4,5-c]-pyridine, 6- cyano-2-(2'-methoxy-4'-methylmercapto-phenyl)-imidazo[4,5-b]-pyridine, 2-amino-8-(2'-methoxy-4'-methylsulfinyl-phenyl)-purine, 2-(2'-methoxy-4'-methylsulfoximino-phenyl)-1H-imidazo[4,5-c]-pyridine , 5-aminocarbonyl-2-(4'-methanesulfonyloxy-2'-methoxy-phenyl)-benzimidazole and 5-acetyl-2-(4'-methanesulfonyloxy-2'-methoxy-phenyl)-benzimidazole their tautomers and their acid addition salts. 3. Procedure according to requirement 1, character! certed by preparing 5 cyano-2-(4'-methanesulfonylamino-2'-methoxyphenyl)-benzimidazole, its tautomers and its acid addition salts. <4>. Method according to claim 1, characterized in that 2-(2'-methoxy-4'-methylsulfonyl-phenyl)-5-acetyl-benzimidazole, its tautomers and its acid addition salts are prepared.