TW384286B - Novel cyclic urea derivatives and their use in inhibiting cell aggregation and thrombosis - Google Patents

Abstract

The invention relates to cyclic derivatives of general formula (I), wherein Ra and Rb are a hetero-bicyclic group with variable subsitution; X is an aliphatic amine with variable optional substituents, Y is a streat C2 to C4 alkyl or alkenyl with variable substituents and the tautomers, the stereoisomers including the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with organic or inorganic acids or bases, which have valuable pharmacological properties, preferably aggregation-inhibiting effects, pharmaceutical compositions containing the compounds and processes for preparing them.

Description

A6 B6 V. Description of the invention (1) The present invention relates to the following formula. Cyclic derivatives

X

N-Rfc γ

(D {Please read the notes on the back first, then Qiwo page} The tautomers are printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs. In the above general formula IX represents a carbodiimide aryl or cyano substituted -2,2-diyl or 1, Y represents a straight chain C2 substituted with Re and Rd, plus 1 or 2 dyne or with 5 to 7 carbons Ortho and Rd substitution, or 1 to Rd substitution with 5 to 7 carbon atoms, or 1,2-arylidene, or 1,2-phenylene, isomers including properties, preferably physiologically acceptable Related to its use and the following: base, as the case may be, or carbonyl, sulfur 1-dicyanoethylene-4 alkane or alkene and its additional base can each carbonyl group 1,2-ring ring mixtures and Its salts, especially the inhibition of aggregation; the nature of inorganic or organic salts, there are; related to the preparation of these compounds. The nitrogen atom is alkyl, aryl, heterocarboxyl, sulfonyl, 1-nitro Ethylene-2,2-diyl; Alkenyl, optionally substituted by Re or Rd or M 1 or 2 alkyl groups, and attached thereto, alkyl, optionally KR. Or! ^ Or 1,2-cycloalkenyl group, as appropriate or M where 1 or 2 methine groups are replaced by nitrogen atoms of each M or where -3 paper is used as much as possible, Η 家 棂 准 (CNS) 甲 4 Specifications (210X297) A6 B6 V. Description of the invention (2) 1 or 2 -CH = CH- groups each M-CO-NH group is replaced or 1 methine M nitrogen atom is replaced and 1- CH = CH- group M-CO-NH group substitution, however the above heterocyclic group may additionally be substituted with 1 or 2 alkyl groups, or-CO-HH-, -HH-CO-, -CH = N -Or- N = CH- group, optionally substituted with R < ^ Rd,

The first group from Re to Rd represents the A-B group, where A is the following formula (Please read the precautions on the back before filling out this page) and printed by the Staff Consumer Cooperative of the Central Standards Bureau of the Ministry of Economy

R2

Ri4v (CH2) n

4--Binding; # This paper size is based on China National Standards (CNS) A4 specifications (210X297 mm) Staff Consumption of the Central Standards Bureau of the Ministry of Economic Affairs A6 _ ^ _ One of the invention description (3) * Among the above The benzo moiety of the hydrazone may be mono-substituted by R25, mono- or di-substituted by R2e, or mono-substituted by MR2B and additionally mono-substituted by R2e, wherein the R2S and R2e substituents may be the same or different and are defined as follows, and Additionally 1 to 3 methine groups may each be replaced by a K nitrogen atom in the above benzo moiety, or -CH = CH- group may be replaced by an M-COH- group, or 1 methine group may be replaced by an M nitrogen atom And one -CH = CH- group 囿 M-CO-HRi substitution, which represents a hydrogen atom or an alkyl group, G da G 4 each represents a bond or a methyl group, which may be K alkyl, aryl or fluorene aryl Single or double substitution, where the substituents may be the same or different, G2 represents a bond or a methyl group substituted with R7 and 1, G3 represents a bond or a methyl group and a substituted methyl group, or 卩 2 When it does not represent a bond, G3 can also represent a carbonyl group,

Gs represents a nitrogen atom or a methine group, optionally substituted by a methyl group, an aryl group, or a heteroaryl group; R2 represents a hydrogen atom or an alkyl group, an aryl group, or a heteroaryl group; if at least one of G2 * G3 does not represent a bond R2 may also represent a hydroxyl group or an alkoxy group, R3 represents a hydrogen atom or an alkyl group, an aryl group or a heteroaryl group, or if at least one of 〇2 and 63 does not represent a bond, R3 and R2- It can represent an oxygen atom, R4 and R14 each represent a hydrogen atom, and a cycloalkyl or cyclofluorenylalkyl, Ci-8-alkyl, C3-e-ene having 3 to 7 carbon atoms each in a cycloalkyl portion (Its alkenyl group may be attached to the nitrogen atom without via a vinyl moiety), or a hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, cyanoalkyl Group, carboxyalkyl group, alkoxycarbonylalkyl group, amidoalkyl group, 5-gaussian standard t® national standard (CNS) A4 specifications (210X297 mm) ......... ........................................ ............................. Install :: ... Order ... Green {Please read the notes on the back before filling in this page) 5. Description of the invention (4) { (Please read the notes on the back before filling this page) N-alkylaminocarbonylalkyl, N, N-dialkylaminocarbonylalkyl, arylfluorenyl, heteroarylalkyl, alkoxycarbonyl , Arylmethoxycarbonyl, formamyl, ethenyl, trifluoroethenyl, allyloxycarbonyl, formamyl or RuCO-O-UuCiUy-O-CO radicals, where RU represents alkyl, Cs-7 cycloalkyl or aryl or arylalkyl, R12 represents a hydrogen atom, alkyl, C5-7 cycloalkyl or aryl, and R13 represents a hydrogen atom or alkyl, or 114 and R3 together represent A straight bond of 2 to 4 carbon atoms is alkylene or, if G2F represents a bond, R4 may represent methylene, R5 represents a hydrogen atom, alkyl, aryl or heteroaryl or if Gi does not represent a bond When Rs can also represent a hydroxyl group or an alkoxy group, or when GL · represents a bond, R4 and Re together can represent another 鐽 and Re represents a hydrogen atom, an alkyl group, an aryl group, or a heteroaryl group, and if (K When R 4 represents a chain and R 4 and R 5 represent another bond, Re may represent an atmospheric atom or a hydroxyl group, a methoxy group, an amino group, an alkylamino group, or a dialkylamino group, or when Gi does not represent a chain. , Re and Rs—can represent oxygen atoms R7 represents a hydrogen atom or an alkyl group, an aryl group or a heteroaryl group,

Ra represents a hydrogen atom or an alkyl group, an aryl group or a heteroaryl group or 1 ^ together with 114 may represent a linear C2-5-alkylene group, R9 represents a hydrogen atom or an alkyl group, an aryl group or a heteroaryl group, or if G2 When it does not represent a bond, Re can also represent hydroxyl or alkoxy, printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs-R10 represents a hydrogen atom or an alkyl group, an aryl group or a heteroaryl group or R10 and R4 can be used together. Represents a straight-chain C2-4-alkylene, R1S represents hydrogen or an amine atom or a fluorenyl group, an aryl group, a heteroaryl group, a mesityl group, and a methoxy group—6 — ^ Paper St rule | China National Standards (CNS)规格 4 specifications (210X297 mm) " " Printed by A6 B6, Shellfish Consumer Cooperative, Central Bureau of Standards, Ministry of Economic Affairs _ V. Description of the invention (5) Base, amine, alkylamine or dialkylamine, Rie Represents a hydrogen atom, a cycloalkyl or cycloalkylalkyl group having 3 to 7 carbon atoms each in a cycloalkyl portion, a Cx-8-alkyl group, a C3-a-alkenyl group (the alkenyl group may not pass through a vinyl group Group is attached to a nitrogen atom), or hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, cyanoalkyl, carboxyalkyl, alkoxy Carbonyl alkyl Aminocarbonylalkyl, N-alkylaminocarbonylalkyl, N, N-dialkylaminocarbonylalkyl or arylalkyl. R17 represents a hydrogen atom or an alkyl group or * If G4 represents a single bond, Rie together with 1-17 can represent another hydrazone, R18 represents a hydrogen atom or an alkyl or, if "represents a bond and Rie and R17 together represent another bond, Ria represents a fluorine, chlorine or bromine atom or a hydroxyl, methyl Oxy, amine, alkylamino or dialkylamino and η represent the numbers 1 or 2, M and B represent a single bond, Che-alkylene, C2-e-alkenyl or arylene, or pyridine Group, cylamidyl group, pyridyl group, or dhamyl group, in which 1 or 2 -CH = N- groups can each be replaced by M-CO-NH- groups and one of the nitrogen atoms can be bonded to the A group The group * is not bonded to a hydrogen atom, however, the above heterocyclyl ring may be additionally substituted by 1 or 2 alkyl groups, or B represents a cycloalkyl group, optionally K1 or 2 alkyl groups may be substituted, or Cs-7- Cycloalkyl, which is optionally substituted by M1 or 2 alkyl groups, and one of them> CH unit is replaced by a nitrogen atom, however, in the above 5- to 7-membered ring, a methyl group adjacent to the nitrogen atom may be substituted by a carbonyl group ; 1 to 1 ^ groups 2 groups representing the following formula, please read the precautions on the back before filling in this page}. Binding • Binding.. 7 — This paper is free to use the Chinese country ¥¥ (〇 胖) A4 specifications (210X297 mm) A6 B6 printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (6) where D represents Ci-e-alkylene, and one methyl group can be an oxygen or sulfur atom or a sulfene Fluorenyl, sulfonyl or "13" groups, or one of them may be replaced by M-C0-NR2O- or -HR2O-C0- groups (where Rie represents a hydrogen atom or an alkyl group, an alkylcarbonyl group, Alkylsulfonyl, arylcarbonyl or arylsulfonyl and R2O represents an argon atom or an alkyl group), or D represents C2-e-alkenyl or arylene, or pyridyl, pyrimidyl, Pyridyl or tacky group * of which 1 or 2 -CH = N- groups can each be replaced by M-CO-NH- groups and one of the nitrogen atoms can be bonded to the E group without being associated with a hydrogen atom The binding condition is that it does not represent a bond by itself or is not adjacent to the D group with a heteroatom or carbonyl group. However, the above heterocyclic group 囿 may be additionally substituted by K 1 or 2 alkyl groups, or D represents an indenyl group. Span , 1,2,3,4-tetrahydronaphthyl or benzocycloheptyl, in which one of the rings is bonded to the E group and the other ring is bonded to a cyclic group of the general formula I, but the saturated ring each It can be substituted by M1 or 2 alkyl groups, and each of the aromatic rings can be a K fluorine, chlorine, bromine or iodine atom or a K alkyl group, a trifluoromethyl group, a hydroxyl group, an alkoxy group, an alkylsulfinylsulfenyl group, an alkylsulfinyl group Fluorenyl, alkylsulfonyl or cyano substituted, or cycloalkyl, optionally K1 or 2 alkyl substituted, or cycloalkyl ** optionally K 1 or 2 alkyl substituted and 1 of them 〉 CH unit M nitrogen atom replacement, but in the above 5- to 7-membered ring immediately adjacent to the nitrogen atom may be replaced by M carbonyl group; or hexahydropyridyl, which is optionally substituted with 1 or 2 alkyl groups, In addition, the methyl group adjacent to the nitrogen atom may be replaced by a carbonyl group; or * If E represents a cyclic imine group, D may also represent 2 to 6 total carbons (read the precautions on the back before filling the nest Page > • Binding. —8 — This paper ft scale + national «standard (CNS) A4 specifications (210X297 mm) ~ printed by the staff consumer cooperatives of the China Standards Bureau of the Ministry of Economic Affairs 7) Atomic An alkylcarbonyl group in which the carbonyl group is bonded to a nitrogen atom of a cyclic imine group of the E group, or, if E does not represent a _, D may represent a bond, E represents a '' bond, or "-β -Alkylene, which may be κ or 2 "-8-alkyl, as C2-4-alkenyl or C2-4-alkynyl, K hydroxyl, amine, aryl or heteroaryl, as Ci-s -Alkoxy or Ci-a-alkylamino, dialkylamino having 2 to 10 total carbon atoms, or KHNR2i or N-alkyl-NR2i group substitution, in which R21 represents an alkyl moiety Alkylcarbonyl or sulfonylsulfonyl groups with 1 to 8 carbon atoms each, alkoxycarbonyl groups with 2 to 5 total carbon atoms, cycloalkanes with 5 to 7 carbon atoms each in the cycloalkyl portion Carbonyl or cycloalkylsulfonyl, or arylalkylcarbonyl, arylalkylsulfonyl, arylalkoxycarbonyl, arylcarbonyl or arylsulfonyl, or C2-e , Or arylene *, or pyridyl, pyrimidyl, pyrimidyl, or daphthyl · As the case may be 1 or 2 alkyl substitution, or C5-7-cycloalkyl, as the case may be Ml Or 2 alkyl substituted, and 1 of them> a nitrogen atom bonded to a carbon atom of the D group of CH unit M Substitution, or C4-7-cycloalkyl, optionally M1 or 2 Cpe-alkyl, MC2 alkenyl or C2-4-alkynyl, Mhydroxy, amine, aryl or heteroaryl, MCi- e-alkoxy or Ci-a-alkylamino, K dialkylamino with 2 to 10 total carbon atoms, or {(-alkyl-NR21 substituted (which (please read the note on the back first) Please fill in this page again on the matter} A 9 A paper ruler comes at 4 B 8 household materials (Which) T4 size (210X297 mm) Printed by the Bayer Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs, A6 __B6 ___ V. Description of the invention (8 R21 is as defined above), or, if D does not represent a bond, the alkylene group is connected to the D group via a W group bond, where W represents an oxygen or sulfur atom or a sulfinyl, sulfonyl group , NR1S, NR2o-C0-, or -CO-NR20- groups, where Rie and R20 are as defined above and the alkylene group may additionally be 1 or 2® Ci-e-alkyl, M C2-4 -Alkenyl or C2-4-alkynyl, hydroxy, amine, aryl or heteroaryl, K Ci-e-alkoxy or alkylamino, M dioxane having 2 to 10 total carbon atoms -Amino, K HNR21 or "-alkyl-NR21 substitutions" in which the heteroatom M of the additional substituent has at least 2 carbon atoms Is separated from the hetero atom of the W group, and R21 is as defined above, and F represents an M hydroxy group, a KCi-e-alkoxy group, a carbonyl group substituted with an arylalkoxy group or a K R22 group, where R22 represents a C4-e-cycloalkyl group or a cycloalkylalkyl group having 3 to 8 carbon atoms in the cycloalkyl portion * wherein the cycloalkyl group may be a Kalkyl group, an alkoxy group, or a dialkylamino group , Substituted with an alkyl group and M1 to 3 methyl groups, and wherein the methyl extension group additionally on a 4- to 8-membered cycloalkyl ring may be substituted with an oxygen atom or a K alkylimino group, or R22 represents Ce-12- Benzocycloalkyl or aryl, or F represents a sulfonic acid group, a phosphonic acid group, a 0-alkylphosphonic acid group, a dialkyltenyl acid group, a tetrazol-5-yl group or R23C0-0-CHR24-0- C0 group, where R23 represents Ci-8-alkyl or Ci-8-alkoxy, cycloalkyl or cycloalkoxy each having 5 to 7 atoms in the cycloalkyl portion, or aryl, aryloxy Group, arylalkyl or arylalkoxy and R24 represents a hydrogen atom or an alkyl group * -10- This paper size is based on China National Standard (CNS) A4 specifications (210X297 mm) ... .......................-.................. ......................................... .......... Order ......... line (please read the notes on the back before filling this page) A6 B6 Ministry of Economic Affairs Printed by the Consumer Standards Cooperative of the Central Bureau of Standards m. Description of Invention (9) and the shortest distance between the F group and the nitrogen atom farthest from the F group on the AB group is at least 11 至少; 3 represents a hydrogen atom, a fluorenyl group, a perfluoroalkyl group, an alkoxy group, a sulfenylsulfinyl group, an alkylsulfinyl group, an alkylsulfonyl group, an amine group, an alkylamine group, and a dialkylamine Group, aryl group, heteroaryl group or arylalkyl group; and the fourth group of 1 ^ to 1 ^ represents a hydrogen atom or an alkyl group or an aryl group; however, unless otherwise stated in the definition of group on M, Each aryl moiety is phenyl, which may be mono-substituted, K R2e mono-, di- or tri-substituted or K mono-substituted and additionally M R2e mono- or di-substituted * where the substituents may be the same or different and R2S represents cyano, carboxyl , Aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkoxycarbonyl, alkylcarbonyl, alkylsulfenylsulfenyl, alkylsulfinylsulfenyl, alkylsulfonylsulfenyl, sulfenylsulfonyl Fluorenyloxy, perfluoroalkyl, perfluoroalkoxy, nitro Amine, alkylamino, dialkylamino, alkylcarbonylamino, phenylalkylcarbonylamino, phenylcarbonylamino, alkylsulfonylamino, phenylalkylsulfonylamine , Phenylsulfonylamino, fluorenyl-alkylcarbonylamino, alkyl-phenylalkylcarbonylamino, fluorenyl-alkyl-benzylcarbonylamino, N-alkyl-alkylsulfonyl Amino, N-alkyl-phenylalkyl-sulfonylamino, N-alkyl-benzylsulfonylamino, aminosulfonyl, alkylaminosulfonyl or dialkyl Aminosulfonyl, and * R2e represents an alkyl, hydroxyl or alkoxy or fluorine, molybdenum, bromine or iodine atom, and if a 2 涸 R2e group is bonded to its adjacent carbon atom * it can also substitute ... ........................................ ............................................................. .... 玎 I. Line (Please read the precautions on the back before filling out this page}; _ 11 A paper at size selected by China National Standards (CNS) A4 specifications (210X297 mm) Central Bureau of Standards, Ministry of Economic Affairs A6 printed by employee consumer cooperatives ____ ^ _ B6 _ ^ _ V. Description of the invention (10) Table C3-e-alkylene, 1,3-butylene, diene-1,4-diyl Or methylenedioxy, and each of the arylidene moieties mentioned in the definition of the above group is phenylene, which may be mono-substituted by M R25, mono- or di-substituted by M R2e, or mono-substituted by K R2S and additionally KR2e-mono Substitution, where the substituents may be the same or different and are as defined above »and the heteroaryl moiety mentioned in the definition of the group on M is a 5-membered heteroaromatic ring containing 1 oxygen, sulfur or nitrogen atom or 1 nitrogen atom and 1 oxygen, sulfur or nitrogen atom, or 2 nitrogen atoms and 1 oxygen, sulfur or nitrogen atom, or 6-membered heteroaromatic ring containing 1, 2 or 3 nitrogen atoms and among them Additionally, 1 or 2 -CH = N- groups may each be replaced by M-C0-NR2o-groups (where R2O is as defined above), and additionally the above heteroaromatic ring may be M1 or 2 alkyl groups Or on the carbon skeleton with K fluorine, chlorine, bromine or iodine or M hydroxyl or alkoxy substituted 9 and unless stated otherwise, the above alkyl, alkylene and alkoxy moieties each have 1 to 4 carbons Atoms and each carbon atom on the above-mentioned alkylene and cycloalkylene moieties are connected to at most one heteroatom bond and tautomers, stereoisomers and salts thereof. However, the preferred compounds of the general formula I above are these, in which: X represents a carbodiimide group, optionally substituted on the nitrogen atom by an M alkyl or cyano group, or X represents a carbonyl, thiocarbonyl or sulfonyl group; Represents a straight bond C2-3 alkylene, which is optionally substituted by Rd or MRdtl I, and which may be additionally substituted by M1 or 2 alkyl groups and wherein an additional methyl group may be substituted by K carbonyl group, -12- This paper uses the national standard (CNS) A4 specification (210X297 mm) {Please read the precautions on the back before filling this page) ...... ...... ~ 3 · .............. Each or Rc and Rd substituent substitution, A6 B6 V. Description of the invention (11) Or a straight-chain C2-3 alkenyl group, optionally M 巳 or Rd and any of them additionally present. Methylmethyl may be carbonyl or 1,2-cycloalkylene having 5 to 7 carbon atoms, depending on Case M 1 or 1 ^, or M 1U and Rd substituted, or 1,2-cycloalkenyl having 5 to 7 carbon atoms, or 1, 2-arylene, or 1,2-phenylene, Wherein 1 or 2 methine groups are replaced by each M nitrogen atom, wherein the heterocyclic group 圑 may be additionally substituted by K1 or 2 alkyl groups, or -CO-HH-, -HH-CO-, -CH = N- orΚΗ-group, if appropriate Μ Rc or Rd substitution, the first one of the! ^ To 1 group represents the A-B group, where A is the following formula (please read the precautions on the back before filling " this page)-install

r2 order.-Mian ... (CH2) n

13 Printed by t Central Standards Consumer Cooperatives of the Ministry of Economic Affairs This paper is printed to the fullest extent. National Standards (CNS) 4 specifications (210 x 297 mm) A6 B6 V. Description of the invention (12 and

16-N only

One of the above R ^ e single or double radicals * which may be substituted by 1 to 3 K-CO-NRi groups in the same part, or K-CO-NRi groups may be substituted or replaced by different methine groups R, represents a hydrogen atom or an alkyl group, and CU each represents a bond or a generation, wherein the Ministry of Economic Affairs and the Central Standards Bureau employee consumer cooperative printed G2 represents a bond or G 3 represents a bond or GB represents a nitrogen atom R2 represents hydrogen One atom does not represent one, R3 represents a hydrogen atom when the substituents M R7 and K Re and or a methine or alkyl bond, or an alkyl group is MR 2 β, each of the system boundaries may be M, or times, wherein the methyl group may be The same R β is substituted for _ R 1 0, and the aryl group R2 may also be substituted or the aryl portion may be mono-substituted as follows: the nitrogen atom may be mono-substituted by 2B, or M, wherein R25 and R2e are substituted, and additionally in the above Benzo substitution, or -CH = CH group can be nitrogen atom and -CH = CH group • It may or may not be the same as the case where it is replaced by M or 雑 fang means hydroxyl 14 This paper is not used in the country • Country Standard (CNS) A4 (210X297 mm) Take 9 groups based on 双: group or aryl single or double, methyl Alkyl or aryl substitution, radical or, if at least radical or alkoxy in 02 and G3, ............ ........................................ ..... ^ ........................ ^ ...................... .. Crepe {Please read the notes on the back before filling in this page) 5. Description of the invention (13) R 4 and each represents a hydrogen atom, and each of the cycloalkyl groups has 3 to 7 carbon atoms Or cycloalkylalkyl, Cxalkyl, C3-e-alkenyl (the alkenyl group may be bonded to the nitrogen atom without a vinyl moiety), hydroxyalkyl, alkoxyalkyl, carboxyalkyl, alkoxy Carbonylalkyl, aminocarbonylalkyl, N-alkylaminocarbonylalkyl, N, N-dialkylaminocarbonylalkyl, arylalkyl, alkoxycarbonyl, arylmethoxycarbonyl, Formamyl, ethylammonium, trifluoroacetamyl, propenyloxycarbonyl, methylcarbyl or RuCO-O-UwCRid-O-CO- groups, where Ria represents Ci-a alkyl, C5-7 cycloalkane Aryl or aryl or arylalkyl, R12 represents a hydrogen atom, alkyl, Cs-7-cycloalkyl or aryl, and Rl3? F hydrogen atom, or 1 ^ 4 and 1 {3—may be a straight bond C2-4-alkylene or * if G2 does not represent a bond, it represents a methyl group; 1U represents a hydrogen atom, an alkyl group or an aromatic group Radical or, if Gi does not represent a bond, hydroxyl or alkoxy or, if Ga represents a chain, * R4 and RB together may represent another bond, and

Re represents a hydrogen atom or an alkyl group or an aryl group, and if Gi represents a bond and Rb- represents another bond, Re may represent an atmosphere atom or a hydroxyl group, a methoxy group, an amine group, an alkylamine group, or a dioxane. Amino group, R · / represents hydrogen atom or alkyl group or aryl group * Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (please read the notes on the back before filling this page) R8 represents hydrogen atom or alkyl group or aromatic group Radicals or Ra and R4- may represent straight-bonded Ca-s-extendyl radicals,

Re represents a hydrogen atom or an alkyl group or an aryl group. If 〇2 does not represent a bond, Re may represent a hydroxyl group or an alkoxy group. A 15 — This paper is a national standard (CNS) A4 specification (210X297). Printed by A6 B6 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (14) R10 represents a hydrogen atom or an alkyl or aryl group, or 1U. Together with R4, it can represent a straight bond C2-4-ethan R15 represents a hydrogen or chlorine atom or an alkyl group, an aryl group, a hydroxyl group, a methoxy group, an amine group, an alkylamino group, or a dialkylamino group. Rie represents a hydrogen atom, each having 3 to 7 on a cycloalkyl portion. Cycloalkyl or cycloalkylalkyl of one carbon atom, (^ -β-alkyl, C3-e-alkenyl (the alkenyl group may be connected to the nitrogen atom without a vinyl group), or hydroxyalkyl, alkoxy Alkyl, carboxyalkyl, alkoxyalkyl, aminocarbonylalkyl, N-alkylaminocarbonylalkyl, N, N-dialkylaminocarbonylalkyl, or arylalkyl, R17 represents a hydrogen atom or an alkyl or, if G4 represents a bond, Rle and R17 together can represent another bond * _ R18 represents a hydrogen atom or an alkyl or, if G4 represents a 鐽 and Rie and 卩 17 together When representing another bond, R18 may represent a fluorine, chlorine or bromine atom or a hydroxyl group, a methoxy group, an amino group, an alkylamino group or a dialkylamino group, and η represents the number 1 or 2, K and B represent a bond Or alkylene or aryl, or pyridyl, pyrimidyl, pyridyl, or daphthyl, where 1 or 2 -CH = H- groups may each be M-CO-NH- groups Substitute, however, the above heterocyclic group may additionally be substituted with K 1 or 2 alkyl groups * or optionally a C 4-7-cycloalkyl group substituted with K 1 or 2 alkyl groups, or (: 3-7-cyclic ring Alkenyl, which is optionally substituted by K1 or 2 alkyl groups, and 1 of them> CH unit M nitrogen atom is replaced, however, in addition, in the above 5 to 7-membered ring, the extended methyl group adjacent to the nitrogen atom may be replaced by M carbonyl group ; The second group to the Rd group represents the following formula ... ............................................... ......... 玎 ........... crape (please read the back first Please note this page before filling in this page) -16- This paper size is in use in a country standard (CNS) A4 specification (210X297 mm) V. Description of invention (15) A6 B6 Employees of the Central Standards Bureau of the Ministry of Economic Affairs Printed by a consumer cooperative where D stands for Ci-e-alkylene • One of the methylene groups can be replaced by a K oxygen or sulfur atom or K sulfinyl, sulfonyl or NRle * 囿, or one of them It can be replaced by M-CO-NR2 (^-NR2O-CO group (where Rie represents a hydrogen atom or an alkyl group, an alkylcarbonyl group, an alkylsulfonyl group, an arylcarbonyl group or an arylsulfonyl group and R2. (Represents a hydrogen atom or an alkyl group), or C2-e-alkenyl or arylene · or pyridyl, pyrimyl, pyridyl, or daphthyl * among which 1 or 2 -CH = N -Each group may be replaced by an M-CO-HH- group, however, the above heterocyclic group may additionally be substituted by K 1 or 2 alkyl groups, or dihydrobenzyl, naphthyl, 1,2,3,4 -Tetrahydronaphthyl or benzocycloheptyl, in which one of the rings is bonded to the E group and the other ring is bonded to the cyclic group 圏 of the general formula I, however the saturated rings may each be substituted by K1 or 2 alkyl groups and The aromatic rings may each be a fluorine, cyano, bromine or iodine atom or an M alkyl group, a trifluoromethyl group, a hydroxyl group, an alkoxy group, an alkylsulfinylfluorenyl group, an alkylsulfinylfluorenyl group, an alkylsulfonylfluorenyl group, or a cyano Or C4-7-cycloalkyl substituted with K1 or 2 alkyl, or (: 5-7-cycloalkyl, optionally K1 or 2 alkyl substituted with 1> CH unit M is replaced by a nitrogen atom, however, in the above 5- to 7-membered ring, a methyl group adjacent to the nitrogen atom may be replaced by a carbonyl group; or a hexahydropyridyl group, which is optionally substituted by M1 or 2 alkyl groups, and wherein A methyl group immediately adjacent to the nitrogen atom may be replaced by an carbonyl group; or, if Ε When representing a cyclic imine group, D can also be said to have 2 to 6 total carbons (please read the precautions on the back before filling this page). Binding. Bookmark-17- This paper is made in China National Standard (CNS) A4 specification (210X297 mm). 5. Description of the invention (16) (Please read the notes on the back before filling this page) Atomyl carbonyl group, the ring of carbonyl group and E group The nitrogen atom of the imine-like imine group is combined, or, if E does not represent a bond, D may also represent a pyrene, E represents a pyrene, or Ci-e-alkylene, which may be 1 or 2 Ci- e-alkyl, hydroxy, amine or aryl, M alkoxy or alkylamine groups each having 6 to 6 carbon atoms, dialkyl amine groups each having 2 to 8 total broken atoms or MHHR21 or fluorene-alkyl-HR21- group substitution, (where R21 represents an alkylcarbonyl or alkylsulfonyl group each having 1 to 6 carbon atoms in the alkyl portion, an alkyl group having 2 to 5 total carbon atoms Alkoxycarbonyl, cycloalkylcarbonyl or cycloalkylsulfonyl, each having 5 to 7 carbon atoms in the cycloalkyl portion, arylalkylcarbonyl, arylalkylsulfonyl, arylalkoxy Carbonyl, arylcarbonyl or arylsulfonyl ), Or C 2-a -alkenyl, or arylene, or pyridyl, pyrimidyl, pyridyl, or daphthyl, optionally substituted with 1 or 2 alkyl groups, or CB- 7-cycloalkyl, which is optionally substituted by K 1 or 2 alkyls, and 1 of them> CH units are replaced with nitrogen atoms bonded to the carbon atom of the D group * or have a cycloalkyl moiety Cycloalkyl groups of 4 to 7 carbon atoms, optionally K1 or 2 Ci-e-alkyl, M hydroxyl, amine or aryl, MCi-e-alkoxy or Cn-alkylamino, M A dialkylamino group or a KHNR21 or a dialkyl-HR21 group with 2 to 8 total carbon atoms (where R21 is as defined above), or if D does not represent a single atom, E may represent a via group Group bond to D-base-18-National paper standard (CNS) A4 specification (210X297 mm) A6 B6 V. Invention description (17) {Please read the precautions on the back before filling the book (Page) an alkyl group of a group, in which W represents an oxygen or sulfur atom, a sulfenyl group, a sulfofluorenyl group, -NRie-, -NRao-CO-, or -C0-NR2o-based group, wherein Rie and R2〇 are based on As defined above and the alkylene group may additionally be M 1 or 2 Ci-e-alkyl M hydroxyl, amine or aryl, M alkoxy or alkylamino groups each having from 6 to 6 carbon atoms, M each dialkylamino groups having 2 to 8 total carbon atoms or K HNR21 or 1 < -Alkyl-NR21- group substitution, in which the heteroatom K of the additional substituent has at least 2 carbon atoms separated from the heteroatom of the W group, and R21 is as defined above, and F represents MH, K Ci-e-alkoxy, Karylalkoxy or K R220 group substituted carbonyl groups (where R22 represents a C4-7-cyclohexyl group or a cycloalkane having 3 to 7 carbon atoms in the cycloalkyl portion Alkyl, in which the cycloalkyl can be substituted with a methyl, alkoxy or dialkylamino group or substituted with an alkyl group and M1 to 3 methyl groups and additionally extending from a 5 to 7 membered cycloalkyl ring A methyl group may be replaced by an M oxygen atom or an M alkylimine group (or R22 represents a benzocycloalkyl group), or a phosphonate group, a 0-alkylphosphonic acid group, a dialkylphosphonic acid group, or a tetrazole-5 -Groups or R23C0-0-CHR24-0-C0 groups, where R23 represents an alkyl or alkoxy group having 1 to 8 carbon atoms each, and a cycloalkane having 5 to 7 atoms each in a cycloalkyl portion Or cycloalkoxy or aryl, aryloxy, arylalkyl or arylalkoxy R24 represents a hydrogen atom or an alkyl group, Ministry of Economic Affairs Bureau of Standards HIGHLAND consumer cooperative printed - and F groups and the shortest distance between the furthest from the group F of the A-B group on the ring nitrogen atom is at least 11 bonds;

The third group from Re to Rd represents a hydrogen atom, an alkoxy group (its alkoxy group cannot be combined with a nitrogen atom), an alkyl group, a trifluoromethyl group, an aryl group, and an arylfluorenyl group. Selection of China National Standards (CNS) A4 (210X297 mm) Printed by A6 B6 of the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (18), thienyl, thiazolyl, pyridyl, pyrimidinyl, Pyridyl or daphthyl; and the fourth from 1 to Rd represents a hydrogen atom or an alkyl group; however, unless otherwise stated, each aryl moiety mentioned in the definition of a group is phenyl. M mono-substituted, κϋ2β mono-, di- or tri-substituted or mono-substituted and additionally substituted with R 2e 箪 or di-substituted, wherein the substituents may be the same or different, and r25 represents cyano, aminocarbonyl, alkylaminocarbonyl, dioxane Alkylaminocarbonyl, alkylcarbonyl, alkylsulfenyl, alkylsulfinyl, alkylsulfonyl or trifluoromethyl and R2e represents alkyl, hydroxy or alkoxy or fluorine, chlorine or bromine Atom, however, if two R2e groups are bonded to their adjacent carbon atoms, it may also represent C3-e-alkylene, 1,3-butadiene- 1,4-diyl or methylenedioxy, and each of the arylene moieties mentioned in the definition of the above group is a phenyl group, which may be monosubstituted by R2S, or substituted by K mono or di, or K R2S mono Substituted and additionally monosubstituted, where the substituents may be the same or different and are as defined above; and unless stated otherwise, each of the above alkyl, alkylene, and alkoxy moieties may each have 1 to 4 carbon atoms and at Each carbon atom on the above-mentioned alkylene and cycloalkylene moiety is connected to at most one heteroatom chain; and tautomers, stereoisomers and salts thereof. Particularly preferred are compounds of the general formula I, where X represents a cyano-substituted carbimide group on the nitrogen atom, or X represents a carbonyl-20. This paper is based on National Standards (CNS) A 4 specifications (210X297 male (please read the precautions on the back before filling this page)-binding. A6 B6 V. Description of the invention (19) group or sulfofluorene group; I γ means ch2ch2-, ch2ch2ciu-, -ch4ch,- CH2CO- or I i -COCH2- group, optionally substituted by MRC or MRC and Rj, or -CO-NH-, -NH-CO-, CH = N- or -N = CH radical, optionally substituted by MCrSRd; The first of the 1 to Rd groups represents an AB-based plaque, where A is the formula

Ri4x (CH2) n

H2C

(Please read the notes on the back before filling in this page)

One, among which the benzo part of the above-mentioned base can be K fluorine, chlorine or bromine atom or κ 21 This paper size is selected from the National Standard (CNS) A4 specification (210X297 mm >) 5. Description of the invention (20) (Please read the notes on the back before filling this page) Alkyl, cyano, trifluoromethyl, hydroxyl, alkoxy substitution, or 1 to 3 methine can each be replaced by K nitrogen atom,

Gi represents a bond or a methyl group * which may be mono- or di-substituted by K alkyl, however the substituents may be the same or different, G2 represents a bond or a methyl group substituted by M 1 {7 and R8, and G 3 represents M 1-9 And R10 substituted methyl, "" means a bond,

Gs represents a nitrogen atom or a methine group, as appropriate, M alkyl substituted, represents a hydrogen atom or an alkyl group, R3 represents a hydrogen atom or an alkyl group, R4 represents a hydrogen atom, and each has 3 to 7 carbon atoms in a cycloalkyl portion Cycloalkyl or cycloalkylalkyl, Ci-e-alkyl, C3-e-alkenyl (the alkenyl group may be bonded to the nitrogen atom without a vinyl group), or hydroxyalkyl, alkoxyalkyl , Carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, alkylaminocarbonylalkyl, N, N-dialkylaminocarbonylalkyl, arylalkyl, alkoxycarbonyl, aromatic Methoxycarbonyl, formamidine, ethenyl, trifluoroethenyl, or RuCO-O-UnCJUd-O-CO- radicals, (where Rn represents an alkyl group, R12 represents a hydrogen atom or a radical, and R13 Represents argon atom), or R4 and R3 together can represent straight chirped (: 2-3-alkylene ·

Rs represents a hydrogen atom or an alkyl or, if Gt represents a bond, IU and RB together can represent another bond, printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs

Re represents a hydrogen atom or an alkyl or, if Gi represents a bond and R5 represents another bond * Re can represent an amine group, R7 represents a hydrogen atom or an alkyl group, -22- This paper uses t National Standard (CHS) T 4 Specification (210X 297 mm) A6 B6 V. Description of Invention (21)

Rs represents a hydrogen atom or an alkane, or Re together with R4 may represent a straight bond C3-4-alkylene, R9 represents a hydrogen atom or an alkyl group, R10 represents an argon atom or an alkyl group, or R10 together with h may represent a straight bond Bond C3-4-alkylene ·

Rm represents a hydrogen atom or an alkyl group, R15 represents a hydrogen atom or an alkyl group,

Rie represents a hydrogen atom or an alkyl group, R17 represents a hydrogen atom or an alkyl group or together may represent another 鐽 * Rie represents a hydrogen atom or an alkyl group or, if 1Ue and R17 together represent another bond, R18 may represent an atmospheric atom or Amine group, η represents the number 1 or 2, and B represents a chain, or alkylene, or aryl, or pyridyl, pyrimidyl, pyridyl, or daphthyl, with 1 as appropriate Or 2 alkyl substituted, or cyclohexyl substituted with KK 1 or 2 alkyl, or hexahydropyridyl, optionally substituted with 1 or 2 alkyl, and which is immediately adjacent to the nitrogen atom Methylene can be replaced by M carbonyl;

The second of the ReMRd group is printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling in this page). F-E-D-where D is the alkylene group. — 23 — This paper is scaled to 8 Chinese Standards (CNS) A4 specifications (210X297 public love) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A6 _B6__ V. Description of the invention (22) or Shenfangji Pyridyl, pyrimidyl, pyridyl, or pyridyl. • K 1 or 2 alkyl substituted as appropriate, or dihydroindenyl, naphthyl, 1,2,3,4-tetrahydronaphthalene Or benzocycloheptyl, in which one of the rings is bonded to the E group and the other ring is bonded to a cyclic group of the general formula I, or optionally a C1-7-cycloalkylene substituted with a K1 or 2 alkyl group Group, or C 5-7-cycloalkyl, which is optionally substituted by 1 or 2 alkyl groups, and wherein 1CH> CH unit M nitrogen atom is replaced, but additionally with nitrogen in the above 5 to 7-membered ring A methyl group adjacent to the atom may be replaced by an carbonyl group; or > If Ε represents a cyclic imine group, D may represent an alkylene carbonyl group, wherein the carbonyl group and the cyclic imine group of the Ε group Nitrogen atom, or if Ε does not represent a bond, D may also represent a bond, Ε: represents a bond, or alkylene, which may be C ^ -e-alkyl or M amine, aryl, alkane Amino, dialkylamino, HNR21 or 1 alkyl-NR21- groups, (where R21 represents an alkylcarbonyl or alkylsulfonyl group each having 1 to 6 carbon atoms in the alkyl portion, Alkoxycarbonyl groups having 2 to 5 total carbon atoms, cycloalkylcarbonyl groups or cycloalkylsulfonyl groups having 5 to 7 carbon atoms each in a cycloalkyl portion, or arylalkylcarbonyl groups, aryl groups Alkylsulfonyl, arylalkoxycarbonyl, arylcarbonyl or arylsulfonyl), or C2-4 • alkenyl 'or arylene, or pyridyl, pyrimidyl, pyridyl Base or extended base, depending on the situation -24- This paper size is free to use China National Standard (CNS) A4 specifications (210X297 mm) ^ ~ .............. ........................................ ..................................... Order ... ............_ (Please read the notes on the back _ then fill in this page) B6 V. Description of the invention (23) 1 or 2 alkyl substitutions * or ( : 5-7-cycloalkyl, which is optionally substituted by M1 or 2 alkyl groups, and 1 of which> CH unit is replaced with a nitrogen atom bonded to a carbon atom of the D group * as appropriate M 1 or 2 Alkyl substituted C4-7-cycloalkyl, or * If D does not represent a bond, E can also represent an alkylene bonded via a W group to a D group, where W represents an oxygen or sulfur atom Or a sulfinyl, sulfonyl, -NR2o-C0- or -CO-NR2 0- group * where R2O represents a hydrogen atom or an alkyl group and an alkylene group may additionally be an alkyl group, or an amine group, an aromatic group Group, alkylamino group, dialkylamino group, HNR21 or N-alkyl-NR21- group substitution * wherein the heteroatom K of the additional substituent has at least 2 carbon atoms separated from the heteroatom of the W group, and R21 Are as defined above, and F represents a hydroxy group substituted with an hydroxy group, an alkoxy group, an arylalkoxy group, or an R220 group (wherein C5-7-cycloalkyl or 5 to 7 in the cycloalkyl portion is represented) Carbon atom cycloalkylalkyl), or R23C0-0-CHR24-0-C0-, phosphonic acid group or 0-alkylphosphonic acid group, in which R23 represents an alkyl group, an alkoxy group, on a cycloalkyl moiety Cycloalkyl or cycloalkoxy and R24 with 5 to 7 carbon atoms each The shortest distance between the oxygen atom or alkyl group, and the F group and the nitrogen atom farthest from the F group on the AB group is at least 11 bonds; printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs {Please read the note on the back first (Fill in this page again)

The third group from Re to Rd represents a hydrogen atom, an alkoxy group (where the alkoxy group may not be bound to a nitrogen atom) or an alkyl group, a trifluoromethyl group, or an arylene group; and the fourth group from Ra to 1 ^ group Represents a hydrogen atom or an alkyl group, but unless otherwise instructed, this paper size uses the Chinese National Standard (CNS) A4 size (210X297 mm). Printed by A6 B6_5 of the Central Laboratories of the Ministry of Economic Affairs. 2. Description of the invention (24) Each of the aryl moieties mentioned in the definition of sulfonium on M is a phenyl group, which may be mono-substituted, mono-, di- or tri-substituted by M R25, or mono-substituted by M 2B and additionally mono- or R 2 e Double substitution, where the substituents may be the same or different * and R2B represents cyano, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkylcarbonyl, alkylsulfenylfluorene, alkylsulfinylfluorene Group, alkylsulfonyl group or trifluoromethyl group and R2e represents an alkyl group, a hydroxyl group or an alkoxy group or a fluorine, chlorine or bromine atom, however, if a 2 涸 R2e group is bonded to its adjacent carbon atom, it may also represent Straight bond C3-4-alkylene, 1,3-butadiene-1,4-diyl or methylenedioxy, and each of the The base moiety is a dibenzyl group, which may be mono-, mono- or di-substituted, or MR2S mono-substituted and additionally MR2e mono-substituted, wherein the substituents may be the same or different and are as defined above, and unless otherwise specified Each of the alkyl, alkylene and alkoxy moieties may have 1 to 4 carbon atoms and each carbon atom on the alkylene and cycloalkyl moieties is linked to at most 1 heteroatom chain; and intervariant Structures, stereoisomers and their salts. Particularly preferred compounds of the general formula I are these, where: X represents a carbonyl or sulfonyl group; Y represents a CH2CH2, CH2CH2CH2, CH = CH, CH2CO or COCH2 group, optionally M1 or 2 methyl substitutions, or Case K Re-substituted CO-NH, CH = N or N = CH groups; the first one from 1 ^ to Rc represents the AB group, where A represents the following formula -26- This paper is based on Chinese national standards (CNS) A4 specifications (210X297 mm) .............. ....- K .................... ...... Order ............ ㉟ (Please read the notes on the back before filling in the book (Page) A6 B6_ V. Description of the invention (25)

r2

: (................................................ ................................................. tr ............._ {Please read the notes on the back before filling out this page} One of the printed products of the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 1: to 2 methine groups in the benzo part of the above-mentioned fluorene may each be replaced by μ nitrogen atoms,

Gi means one key or extension of methyl, G 2 means one key, -27- The paper ruler is free to take off the national standard (@S) A4 size (210X297 mm) Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Preparation of A6 B6 V. Explanation of the invention (26) G3 represents methylene, G 4 represents 7F—bond, 05 represents nitrogen atom or methine, R 2 represents hydrogen atom, R 3 represents nitrogen atom, R 4 represents hydrogen atom, ring Propyl or cyclopropylmethyl, Ci-e-alkyl or allyl, hydroxymethyl, carboxyalkyl, alkoxycarbonylalkyl or benzyl, RB represents a hydrogen atom,

Re represents a hydrogen atom, R14 represents a hydrogen atom or an alkyl group * R1B represents a hydrogen atom or an alkyl group,

Rie represents a hydrogen atom or an alkyl group, R17 represents a hydrogen atom or Rie and 1 ^ 7 together can represent another bond, R13 represents a hydrogen atom or • If Rle and "7 together represent another bond, R18 can represent an amine group , Η represents the number 1 or 2, and B represents a bond or a phenylene group, and the second 1 of the 1 to 1 group represents a group of the formula F_Ε_D_ where D represents an alkylene group, or a phenylene group , Or cyclohexyl, or hexahydropyridyl, in which the ring nitrogen atom and the E base are replaced as appropriate — 2 8 —. This paper is in use. National Standards (CNS) A 4 Specifications (210X297 mm) ............ ......................................................... ............... 玎 .................... ^ (Please read the notes on the back before filling this page) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs · A6 _._, _B6_. V. Description of the Invention (27) Linear alkylene chain coupling, or a bond, E means linear alkylene group, which can be M alkyl group Or phenyl substituted, or C2-4 diphenyl, or phenyl, or if D does not represent a bond, E may represent a bond to the D group via an oxygen atom Straight-chain 0-alkylene, and F represents a K-hydroxy or alkoxy-substituted carbonyl group, and the shortest distance between the F group and the nitrogen atom farthest from the F group on the A-B group is at least 11 bonds ,with

The third from the Re to the IU group represents a hydrogen atom, an alkalkoxy group may not be bonded to a nitrogen atom) or an alkyl group or a phenyl group; however, unless specified elsewhere, the above alkyl, alkylene, and alkoxy moieties Each may have 1 to 4 carbon atoms and each carbon atom on the above-mentioned alkylene and cycloalkylene moiety is linked to at most 1 heteroatom chain; and tautomers, stereoisomers and salts thereof. Particularly preferred compounds of the general formula I are these, where X represents a carbonyl group; Y represents a CH2CH2, CH2CH2CH2, CH = CH, CH2CO or COCH2 base, or optionally a M-substituted N = CH group; 1 group The AB group, where Λ is the following formula: 29- This paper size is in accordance with Chinese National Standard (CNS) A4 specification (210X297 mm) {Please read the precautions on the back before filling this page) • Binding. A6 B6 V. Description of Invention (28)

r2

Install .....................:-玎 ............, line (please first Read the note on the back and fill in this page again.} One of the products printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs, where 1 or 2 methine groups in the benzo portion of the above group can each be replaced by μ nitrogen atoms

Ga means one bond or methyl group. -30- This paper size is based on Chinese National Standard (CNS) A4 (210X297 mm) alkyl, or allyl or benzyl A6 B6. 5. Description of the invention ( 29) 〇2 means 鐽 * G3 means methyl, G 4 means one bond,

Gs represents a methine group, R2 represents a hydrogen atom, and R 3 represents a hydrogen atom.

R1S represents a hydrogen atom,

Rle and R17 represent a bond, R18 represents a hydrogen atom or an amine group, and η represents the number 1, and B represents a bond; the group represents a group of the formula F-E-D-where D represents a CH2CH2 group, Or 1,4-phenylene, or 1,4-cyclohexyl, E represents optionally a methyl substituted CH2CH2 group, CH = CH, 1,4-phenylene or 0-CH2- Among them, the oxygen atom of the 0-CH2- group is bonded to the D group, and 31 paper sizes are in use. National Standard (CNS) A4 specification (.210X297 mm) ........ ........................................ .......................... (Please read first Note on the back of the page to refill this page} Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs. Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs. The shortest distance between the alkoxy-substituted carbonyl group and the F group and the nitrogen atom farthest from the F group on the AB group is at least 11 bonds; Examples of particularly preferred compounds mentioned under M : (A) 1- [4- [2- (methoxycarbonyl) ethyl] phenyl] -3- (1,2,3,4-tetrahydroisoquinolin-6-yl) -tetrahydroimidazole -2- 醑, (b) [4- (2-carboxyethyl) benzyl] -3- (1,2,3,4-tetrahydroisoquinolin-6-yl) -tetrahydroimidazole-2 -Ketone, (c) [4- (2-carboxyethyl) phenyl] -3- (2-methyl-1,2,3,4-tetrahydroisoquinolin-6-yl) -tetrahydro Imidazole-2 -one, (d) 1- [4- [2- (isobutoxycarbonyl) ethyl] phenyl] -3- (1,2,3,4-tetrahydroisoquinolin-6-yl ) -Tetrahydrooxazol-2-one, (e) 1- [4- (2-carboxyethyl) phenyl] -3- (2,3,4,5-tetrahydro-1H-3-benzo Heptaazine-7-yl) -tetrahydrooxazol-2-one, (f) 1- [4- [2- (methoxycarbonyl) ethyl] phenyl] -3- (2,3, 4,5-tetra argin-1H-3 -benzo-nitrogen ~ seven group'-7-yl) -tetrazolium-2-fluorene, U) 1- [4- [2- (isopropoxycarbonyl ) Ethyl] benzyl] -3- (2,3,4,5-tetrafluorene-1H-3-benzodiazepine-7-yl) -tetrahydroimidazol-2-one, (h) Bu [4- (2-carboxyethyl) benzyl] -3- (3-methyl-2,3,4,5-tetrahydro-1H-3-benzodiazine-7-yl) -tetra Hydroimidazol-2-one, (i) 4- [4- [2- (carboxyethyl) phenyl] -5-methyl-2- (2,3,4,5-tetrahydro-1H-3- Benzotriazine-7-yl) -4fluorene-1 2,4 -triazol-3-one, -32- This paper size uses the Chinese National Standard (CNS) A4 specification (210X297 mm) {Please read the precautions on the back before filling this page)-Pack. Order; B6 V. Description of the invention (31) {Please read the notes on the back before filling this page) (j) 1- [trans-4- (2-carboxyethyl) cyclohexyl] -3- (2,3 , 4,5-tetrahydro-1H-3-benzodiazepine-7-yl) -tetrahydroimidazol-2-one, (k) 1- [4- [2- (methoxycarbonyl) ethyl Phenyl] phenyl] -3- (3-methyl-2.3.4.5-tetrahydro-1H-3-benzodiazepta-7-yl) -tetrahydroimidazole-2 -one, (l) 1- [4- [2_ (ethoxycarbonyl) ethyl] phenyl] -3- (3-methyl- 2.3.4.5- tetrahydro-1H-3-benzomonoazine-7-yl) -tetra Hydroimidazole-2-fluorene, (m) 1- [4- [2- (isopropoxycarbonyl) ethyl] phenyl] -3- (3-methyl- 2.3.4.5- tetrahydro-11 ^- 3-Benzoazine-7-yl) -tetrahydroimid-2-one, (η) 1- [trans-4- (2-carboxyethyl) cyclohexyl] -3- (3-methyl -2.3.4.5- tetrahydro-1H-3-benzylazine-7-yl) -tetrahydroimidazole-2 -fluorene, (ο) 1- [trans-4- [2- (isopropyloxy Carbonyl) ethyl] cyclohexyl] -3- (3-methyl-2,3,4,5-tetrahydro-111-3-benzotriazine-7- ) -Tetrahydropyridine-2 -pyrene, (p) 1- [trans-4- [2- (ethoxycarbonyl) ethyl] cyclohexyl] -3- (3-methyl-2,3,4 , 5-tetrahydro-111-3-benzodiazepam-7-yl) -tetrahydroimidazole-2 -fluorene, printed by the Consumer Cooperatives of the Central Standards Bureau, Ministry of Economic Affairs, U) 1- [反 -4- [ 2- (methoxycarbonyl) ethyl] cyclohexyl] -3- (3-methyl-2,3,4,5-tetrahydro-111-3-benzo-azahepta-7-yl)- Tetrahydroimidazole-2-Moe, (r) 1- [trans-4-[(carboxymethyl) oxy] cyclohexyl] -3- (3-methyl- -33- winter paper standard (CNS) A4 specifications (210X297 mm) B6 V. Description of the invention (32) 1 2,3,4,5-tetrahydro-1H-3-benzo-nitroazine-7-yl) -tetrahydroimidazole -2 -ketone, | (s) 3-[trans-4- (2-carboxyethyl) cyclohexyl] -1- (3-methyl-2,3,4,5 -tetrahydro-1H-3- Benzoazine-7-kib allantoin and (t) 1- [trans-4- (2-carboxyethyl) cyclohexyl] -3- (3-ethyl-2,3,4, 5-tetrahydro-1H-3-benzo-nitroazahepta-7-yl) -tetrahydrooxazol-2-one, and tautomers and their salts. The new compounds of general formula I according to the present invention can be K * For example, the following methods are prepared: a) In order to prepare compounds of general formula I, where F represents a carboxyl group: compounds of the following formula (please read the precautions on the back before filling this page) )

X

y Printed by Shellfish Consumer Cooperative, Central Bureau of Standards, Ministry of Economic Affairs (of which 丨

I

I

Re, Rb, X, and Y are as defined above, and their conditions are that one of the radicals represents the F'-ED group, where E and D are as defined above, and F * represents hydrolyzable, K acid-treated, pyrolyzed or decomposed groups converted to carboxyl groups) into compounds of general formula I, where F represents a carboxyl group. For example, functional derivatives of carboxyl groups such as unsubstituted or substituted fermented amines and esters, a 34 — this paper size is used in China B country standard (CNS) A4 grid (210X2W mm)> 5. Description of the invention ( 33) A6, B6, Ministry of Economic Affairs, Central Bureau of Standards, Benxi Cooperative Co., Ltd., printed thioesters, 3M hydrolyzed transesterified acid esters, which can be hydrolyzed to sodium trifluoroacetate or hydrogen, water / ethyl water / dioxygen, and the reaction solution in the above An imino group such as an amine group. If any ethoxyl is present, if F 'is in the group, it can be sulfuric acid. If F' is in tributylisobutyric acid or poly, benzene, methyl-10 1C, or by heating methyl silicide to carboxyl or pyrolysis hydrogen Decompose the reaction of trifluoro with appropriate or mixed potassium oxide alcohol and boiling temperature in the six-group of water in the presence of nitric acid of formula II in the presence of nitric acid of formula II. Benzene and ethyl 120t: Esteryl esters, orthoesters, imide groups * tertiary esters are converted to carboxyl groups and converted to carboxyl groups. In the presence of an acid such as hydrochloric acid or sulfur solution, or in the presence of an appropriate isopropyl alcohol, formazan, at a temperature between -lot and 120 ° C, any acetamidine is present Imino group can be converted to organic acids such as trichloroethyl hydroxyl can be simultaneously converted into esters, hydrazones or anhydrides, or nitriles, such as the third butyl ester, aralkyl alcohol esters> such as benzyl acid, phosphoric acid, tris Chloroacetic acid or a solvent such as water, water / formaldehyde, water / tetrahydrofuran, or an intermediate in a base such as lithium hydroxide, hydroxide, for example, N-fluorenylamino or N-fluorenyl at room temperature When the corresponding amine or acetic acid or trifluoroacetic acid is treated during the treatment of the corresponding alkoxy group such as cyano or amine carbonyl group in the trifluoro compound, such base salts such as sodium nitrite can be suitably dissolved simultaneously in the acid, Converted to carboxyl at temperatures between 0 and 50 t: When the compound represents, for example, a third butoxycarbonyl group, such as trifluoroacetic acid, formic acid, p-toluenesulfonic acid, sulfuric acid, and aryl, as appropriate, in an angry solvent such as dichloromethane, gas-form ether, tetrahydrofuran or dichloromethane. Within the oxygen six paintings, it is preferred to lyse at a temperature of between 0 and 60 ° in an inert solvent such as dichloromethane, chloroform, benzene, and chloroform. This paper uses Chinese national standards ( CNS) A4 specifications (210X297mm) (please read the precautions on the back before filling in this page). Binding and binding: Α6 Β6 V. Description of the invention (34) Benzene, tetrahydrofuran or dioxin, and more than Preferably in the presence of a catalytic amount of acid such as p-toluenesulfonic acid, sulfuric acid, phosphoric acid or polyphosphoric acid, it is preferably cracked at the boiling temperature of the solvent used, for example, between 40 t: to 100 ° C. In the above-mentioned Under the reaction conditions, any N-tertiary butoxycarbonylamino group or N-tertiary butoxycarbonylimino group present can be converted into the corresponding amine or imino group if F 'in the formula can In hydrogenated catalysis, ethanol / amidine, the hydrogen pressure is more than 5 bar at the same time, and N-benzyloxycarbonyl b) In order to make a bond, epimethoxy, amine or dialkylamine will be represented in the compound of formula 11 below, for example, benzyloxycarbonyl " benzyl is also suitable in the presence of Pd / C, as appropriate Solvents such as formic acid, ethyl water, glacial acetic acid, ethyl acetate, dioxane, or dimethylformate are preferably at a temperature between 0 and 50 ° C, for example, at room temperature, at 1 to 2 under hydrogen cleavage. During the hydrogenolysis, other radicals can also be present, such as nitrocokanogen to amine or benzyloxycokan to hydroxyamine, N-benzylimine, N-: benzyloxycarbonylamine The radical or imino group can be converted into the relative amidine or imino group. Compounds of general formula I, in which Rle and R17 together represent another bond and in R1S or R18 groups, at least: at least one represents a hydroxyl group, a group, and has 1 to 4 alkyl groups; an alkyl group of carbon atoms Amino group: Please read the precautions on the back before filling out the book}-Installed by the Central Consumers Bureau of the Ministry of Economic Affairs and printed by the Consumer Cooperative

RaN

N-Rb m (of which 36: this paper is used to the fullest extent possible in the Central and China National Standards (CNS) A4 specification (210X297) *) 5. Description of the invention (35)

Ra, Rb,) (and Υ are as defined above, with restrictions: conditions are L to L groups: one represents the A-B group 其中, where | B is as defined above and 'A represents a group of the formula

N

(Please read the notes on the back before filling in this page.) The benzo part and Gs are as defined above * B 1 and 22, which may be the same or different * Each represents a nucleophilic leaving group such as a tooth atom, such as chlorine Or bromine atom, but the Zα-based painting can also have the meaning given above or the 叾 2 group can have the meaning given above by Rie) React with compounds of the formula (IV) Central Standards of the Ministry of Economic Affairs M Member X Consumer Cooperative Wherein R27 represents a hydroxyl group, a methoxy group, an amino group, a methylamino group, an ethylamino group, an alkylamino group or a dialkylamino group having 1 to 4 carbon atoms in the alkyl portion. The reaction is conveniently performed in solvents such as water, propyl alcohol, ethanol > tetrahydrofuran, dioxane 37 paper size tB national standard (CNS) f 4 specifications (210x297 mm) printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 2. Description of the invention (36) Liu Xing, dimethylformamide or dimethylimine, but in the case of the compound of the general formula IV as dissolved I, if appropriate, and in a base such as sodium hydroxide, In the presence of potassium hydroxide, potassium carbonate, ammonium sodium or hydrogenation, it is carried out at a temperature between 0 and 250 t :, but preferably at a temperature between 50 and 225 t :. I c) In order to prepare a compound of the general formula I, in which 11 0 and 0 represent another m 丨 4 represents a 鐽 and Rle represents a methane or bromide: a compound of the following formula.

(V) (where I, Rb, X, and Y are as defined above, and the restriction is that one of 1 ^ to Rd represents the AB group, where ί is as defined above and A represents the base of the formula Mission 0,

The benzo part and g5 are as defined above and 38 {Please read the notes on the back before filling this page} B6 V. Description of the invention (37) R15 'represents a hydrogen atom or an alkyl or aryl group representing the aforementioned R1S ), React with acid halide. The reaction starts from an acid halide such as oxophosphorus or oxybromide, optionally in the presence of a solvent such as benzene, dioxobenzene, nitrobenzene, or tetraoxocarbon, and optionally the corresponding salt of a hydrohalide In the presence of sodium cyanide or sodium bromide, the temperature is raised between 50 and 250 t: but preferably at the boiling temperature of the reaction solution. d) For the preparation of compounds of the general formula I, wherein X represents a cyano-substituted carbonimino or carbonyl or sulfonyl group and Y represents W R as appropriate. Or a straight C2-4-alkylene substituted with M or ^ and Rd: cyclize a compound of the formula X '(Please read the precautions on the back before filling this page)

R

NIN —R. I U. b (VI) Central Standards Bureau of the Ministry of Economic Affairs X Consumer Cooperatives where 1? »And Rb are as defined above, Xf represents a cyano-substituted carbodiimide or carbonyl or sulfonyl group *" Or one of the ^ groups represents a hydrogen atom and the other of the ^ or! ^ Groups represents, as the case may be, M Rc or Rd, or a straight bond C2-4-alkylene substituted with M 1U and Rd, to the end of the additional Associated nucleophilic leaving group such as a halogen atom, a hydroxyl group or a sulfonic acid ester, such as a chlorine, bromine or iodine atom or a hydroxyl group, a methylsulfonyloxy group or a p-toluenesulfonyloxy group. The reaction is preferably in a solvent such as dioxo Methane, acetonitrile, tetrahydrofuran, toluene, dimethylformamide or dimethyl methylene chloride, as appropriate, in bases such as sodium hydride, 39, this paper is applicable in China National Standard (CNS) A4 specifications (210X297) 1 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs. 5. Description of the invention (38) In the presence of potassium carbonate, third potassium butoxide, or N-ethyldiisopropylamine, or a dehydrating agent such as triphenyl, as the case may be. In the presence of phosphine / diethyl azodicarboxylate, a temperature between -20 and 100 υ, preferably between 0 and 60 1C E) In order to prepare a compound of general formula I, where X represents a carbonyl group and Y represents one of the above-mentioned alkylene or alkylene groups: a compound of the formula Rze-HH ~ T is reacted with an isocyanate of the formula (VII) (VIII) (wherein one of the R2e or R2e bases has the meaning given above as Re and the other Rb of the Rze or R2e group has the meaning given above and T represents a group of the formula-(CH2) »-HC (0R3〇) 2 optionally substituted with or Rd or .Re and Rd on the alkylidene moiety, where m represents the number 1, 2 or 3 and 30 feet (Table Cl-4_), -40- the size of this paper 逋National standard (CNS) A4 specification (210X297 mm) {Please read the precautions on the back before filling in this page) V. Description of the invention (39 Response 200 t as the case may be: The temperature of acetic acid fermentation and ethanization is increased to room temperature to 5 bar in the presence of f). For the G3 generation IU atom or hydrogenation, the subsequent temperature is inert, depending on the situation. The reaction can also be performed in formula V 11 It is converted into intermediates, p-toluene sulfonate, and tetrahydrofuran, and then hydrogen, and the temperature is between 50 ° C and 100 ° C. The hydrogen pressure under the temperature is used to prepare the general formula epimethyl, table hydrogen atom, C 1-4 _ compound of the formula hydrogenation as a solvent, preferably without a solvate and an open-bonded acid or sulfan or di Subsequent conversions are carried out at methanol and acid at a temperature of (1) as appropriate and 1 to 3 and 0 to 2 dioxane at 20 to 160. Glands of general formula VIII * in the presence of acid if the presence of acid is needed. 'Formation of the desired argon acetic acid, acetic acid 0 to loot: between 1 and 7 bar A6 B6 or: toluene * within 20 to t: It is performed at a temperature in between. The reaction of isocyanate may be carried out in the presence of an acid such as acetic acid, tris, and optionally a solvent such as formazan at 0 t: to the boiling product of the reaction solution. In catalysts such as Pd / C or platinum ethyl acetate or glacial acetic acid, depending on the temperature, but preferably under hydrogen pressure * but preferably 3 compounds, where G2 each represents a bond M C1-4-焼 Re , It can be replaced by beryl, same or different, R4 and each representative hydrogen (please read the notes on the back before filling in this page)

Ra-N

N-Rb

(DO 41 This paper size is in accordance with China National Standards (CNS) specifications (210X297mm) A6 B6 V. Description of the invention (40) Among which 1U, Rb, X and Y are defined as above * The restriction is R -One of the Rd groups represents the AB group, where B is as defined above and: IA represents a group of the formula 丨

Printed by the Shell Standard Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs, where the benzo part is as defined above, I GB Different, each: represents a hydrogen atom or argonization preferably in a suitable solvent such as methanol, formic acid / water, acetic acid, ethyl acetate, ethanol, ether, tetrahydrofuran, dioxane or dimethylformamide , K hydrogen in the presence of hydrogenation catalysts such as Raney nickel, platinum, platinum dioxide, rhodium or Pd / C, and optionally add an acid such as hydrochloric acid, at a temperature between 0 and loot :, preferably 20 to 80 ¾ Intertemporal temperature. Any optionally substituted exene gene present in a compound of general formula IX can be converted into ... ........................................ .............. Order ........ Weft (Please Read first + read the precautions on the back and then fill in this page.) 42- This paper size is t 遑 揉 揉 揉 揉 (CNS) A4 size (210X297 mm) 'B6 V. Description of the invention (41) Depending on the situation Substituted alkylene. I'g) For the preparation of compounds of the general formula I, in which F represents a carbonyl group, Ci-e-alkoxy, arylalkoxy (having 1 to 4 carbon atoms in the alkoxy moiety and wherein aryl The moieties are as defined above), or the MR22 radical is substituted: a compound of the formula

(X) Printed by the Shellfish Consumer Cooperative of the Central Bureau of Standards and Quarantine of the Ministry of Economic Affairs (where Re, Rb, X, and Y are as defined above, and the restriction is that one of the 1 to Rd groups represents the F "-ED group, Where E and D are as defined above and F " represents a carboxyl group or an alkoxycarbonyl group) is reacted with an alcohol of the formula HO-R31; (XI) in which 31 has the meaning given above as 1? 22 as indicated above # represents Cn-alkane Or arylalkyl, in which the aryl part is as defined above, and the alkane: base part can have 1 to 4, 43, Feng Zhi "to the fullest extent possible, using China National Standard (CNS) A4 specifications ( 21〇 × 297mm) ............... ............................................................ ............. 玎 ............., (Please read the precautions on the back before filling this page) Printed by A6 —__ B6__ from the Central Bureau of Standards of the Ministry of Economic Affairs —__ B6__ V. Description of the Invention (42), • ^. Carbon atom. The reaction of carboxyl compounds depends on the solvent or solvent mixture, such as methane and dimethyl formamidine, as appropriate. Amine, benzene, toluene, benzene, tetrahydrofuran, benzene / tetrahydrofuran or dioxane * or particularly advantageous In the corresponding alcohol of the general formula XI, optionally in the presence of an acid such as hydrochloric acid or in the presence of a dehydrating agent, such as isobutyl chloroformate, tetraethyl orthocarbonate, trimethyl orthoacetate, 2 , 2-dimethoxypropane, tetramethoxysilane, sulfenyl chloride, trimethyl aluminosilane, sulfuric acid, methanesulfonic acid, p-toluenesulfonic acid, triammonium hydrazone, osmium pentoxide, osmium, N '-Dicyclohexylcarbonyldiimide, Ν, ΙΓ-Dicyclohexylcarbonyldiimide / 1-hydroxybenzotriazole, N, N'-Dicyclohexylcarbonyldiimide / N-carbonylsuccinimide , N, fT-carbonyldiimidazole or triphenylphosphine / tetraaminated carbon, and optionally a base such as pyridine, 4-dimethylaminopyridine or triethylamine, conveniently at 0 to 150C The temperature is preferably between 0 and 100 ° C. The reaction between the corresponding alkoxycarbonyl compound and the alcohol of the general formula XI is preferably in the corresponding alcohol as a solvent, as the case may be In the presence of a further solvent such as methane or ether, preferably in the presence of an acid such as hydrochloric acid * at a temperature between 0 and 1501 :, preferably at a temperature between 50 and 100T. H) For the preparation of compounds of the general formula I, in which one of the R4, R14 or Rie groups represents an optionally substituted alkyl, alkenyl, cycloalkyl, naphthenic group in the above definition of R4, R14 or Rie groups One of alkyl group or aralkyl group: The compound of the following formula —44 —-. ', Deep into the paper, the scale of the paper uses the Chinese National Standard (CNS) A4 specification (210X297 mm) ... ........................................ ............................................................. .... Order -.............. (please read the precautions on the back before filling out this page) 5. Description of the invention (43)

A6 B6 (where; I Re, Rb, X, and Y are as defined above and their limitations! The condition is that one of the R · to Rd radicals represents the AB group, where A and B are as defined above and their limitations The conditions are that IU and Rle each represent an argon atom.) Reaction with a compound of the formula Z3-R32 (XIII) {Please read the precautions on the back before filling this page}. Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs / 1 wherein R32 represents ί-β-alkyl, cycloalkyl or cycloalkylfluorenyl, wherein the cyclofluorenyl moiety may have 3 to 7 carbon atoms and the alkyl moiety may have 1 to 4 carbon atoms, C3- e-alkenyl or arylalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, N-alkyl! Aminocarbonyl Alkyl or N, N-dialkylaminocarbonyl, wherein the aryl and alkyl moieties are as defined above * and Z3 represents a nucleophilic leaving group such as a halogen atom, such as a chlorine, bromine or iodine atom or a sulfonate, For example, methylsulfonyloxy or p-toluenesulfonyloxy, or 23 together with the adjacent hydrogen atom of the R32 group represents an oxygen atom. With the alkylation of the compound of the formula XIII in which Z3 represents a nucleophilic cleavage group, the paper size is in Chinese paper standard (CNS) A4 specification (210 X 297 mm) A6 B6 5. Description of the invention (44) Favorable in solvents such as dioxane, methane, tetrahydrofuran, dioxane, dimethylarene or dimethyl methyl etheramine, optionally in the presence of a base such as sodium carbonate, potassium carbonate or sodium oxide solution Or in a tertiary organic base such as N-ethyldiisopropylamine or N-methylmorpholine, which can be used as a solvent at the same time, in the presence of .i, at a temperature between -30 and 150, but preferably At temperatures between 20 and 120 υ

Ionizing alkylation with carbonyl compounds of general formula XIII in the presence of hydrogenated metal compounds such as sodium borohydride, lithium hydrogen hydride or sodium cyanoborohydride, conveniently at t >6-7; H and at room temperature, or in the presence of a hydrogenation catalyst, such as M hydrogen in the presence of Pd / C • under hydrogen pressure of 5 bar. However, the methylation is preferably carried out in the presence of formic acid as a kanogen at elevated temperatures, such as between 60 and 120 υ. i) In order to prepare a compound of general formula I, where X represents a carbimide, which is substituted on a nitrogen atom with a cyano group, or X represents a carbonyl or a sulfonyl group, a compound of the formula: ........................................ ................................... ..... Green. (Please read the notes on the back before filling in this page)

γ Printed by the Consumer Cooperative of the China Standards Bureau of the Ministry of Economic Affairs and the compound of the following formula λ-R34 (XV) _ 46 —taa t4 * «· (210x297 ^) A6 B6 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs | Five (45) (wherein Y is as defined above, X "represents a carbodiimide group substituted by a nitrogen atom of K cyano, or X" represents a carbonyl group or a sulfonyl group, and one of R33 or 1134 Re has the meaning given above, and another Rb of the R33 or R34 group has the meaning given above, and Z 4 represents a nucleophilic leaving group such as a halogen atom, a hydroxyl group or a sulfonic acid, such as fluorine, atmosphere, bromine or iodine. Atom or methylsulfonyloxy or p-toluenesulfonyloxy). The reaction is preferably in a solvent such as dichloromethane, ethyl acetate, tetrahydrofuran, toluene, pyridine, dimethylmethosamine, dimethyl 5S or N-methylpyrrolidine, optionally in one or more bases. Such as hydrazone, potassium carbonate, potassium third butoxide, N-ethyldiisopropylamine, tri- [2- (2-methoxyethoxy) ethyl] amine or Ν, Ν, ΙΓ, ίΓ -In the presence of tetramethylethylene diamine, and optionally in the presence of a dehydrating agent such as triphenylphosphine / diethyl azodicarboxylate * and optionally in copper powder or 1 or more copper salts For example, in the presence of the iodide subnet as a reaction accelerator, at a temperature between -20 and 250¾, but if Zn4 is bonded to an aliphatic carbon atom, it is preferably at a temperature between 0 and 60 ° C. If Z * and aromatic When carbon atoms are bonded, or at a temperature between 60 and 180 t: However, in this case, Z4 can only represent a halogen atom. J) For the preparation of compounds of the general formula I, in which IU or R14 represents an alkoxycarbonyl, arylmethoxycarbonyl, formamyl, ethenyl, trifluoroethyl, propyleneoxycarbonyl or RuCO-O- UwCRid-O-CO group, in which Ru to R13 and aryl part are defined as above and the ethoxy part can have 1 to 4 _ 47- This paper uses China National Standard (CNS) A4 specification ( 210X297 mm) ^ '............................ ............................................... ...... 玎 ........................ {Please read the notes on the back before filling in the book Page) A6 B6 V. Description of the invention (46) 㑩 Carbon atom: the compound of the following formula

Ra-N

N_Rb Printed by the Ministry of Economic Affairs t Central Standards Bureau X Consumer Cooperatives (where Re, Rb, X, and Y are as defined above, and their restrictions are _ shown as hydrogen atoms) react with a compound of the formula Zb-R 35 (XVII) Wherein R3B represents an alkoxycarbonyl group having a total carbon atom of 2 to 5 㑩, wherein the aryl part is an arylmethoxycarbonyl group as defined above, or a methyl group, an ether group, an acryloxycarbonyl group, RuCO-OU ^ CRid-tHCO or trifluoroacetamyl, where Ru to R13 are as defined above, and ZB represents a nucleophilic leaving group such as a halogen atom or aryloxy, arylthio, alkoxy, alkoxycarbonyloxy , Aralkoxycarbonyloxy, or N-oxazolyl • such as a gas or bromine atom or 4-nitrobenzyloxy. The fermentation effect is conveniently in solvents such as tetrahydrofuran, dichloromethane, dichloromethane, 48 papers, Λ degree free use, country t country, iC | NS), .4 specifications (2 ^ × 297 public gold) v ___________________________________________ '....................................... .............. * May + ........! (Please read the notes on the back before filling in this page) Α6 Β6 5. Description of the invention (47) In a mixed solution of dimethylformamide, water or its solvent, as appropriate, in the presence of a base such as sodium carbonate, potassium carbonate or sodium hydroxide solution 1, or a tertiary organic base Such as triethylamine, N-ethyldiisopropylamine, N-methylmorpholine or pyridine, which can be used as a solvent at the same time, in the temperature range of -30 to 10,000 t: It is preferably carried out at a temperature between -10 and 60¾.丨 k) In order to prepare a compound of general formula I, where F represents a truncated group * which is alkoxy, M aralkoxy (where the aryl moiety is as defined above and the alkoxy moiety may have 1 to 4 carbons Atom), or M or R23C0-0CHR240 group substitution, in which R22 to "24 is as defined above * will be the compound of the following formula (please read the precautions on the back before filling the page)

R * -N

The central standard of the Ministry of Economic Affairs of the Ministry of Economic Affairs, M Be X Consumer Cooperatives (where ·, Rb, X, and Y are as defined above, and their restrictions are R «• to Rd. The base represents F '' '-ED basis, Where E and D are as defined above and:

I

IF represents a carboxyl group) | Reacts with a compound of the following formula. 49 This paper size uses the Chinese National Standard (CNS) f 4 specifications (210X297 mm) A6 B6 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs. ) Ze-R3e (XIX) where R3e represents Ca-e-alkyl, arylalkyl (where the aryl moiety is as defined above and the alkyl moiety may have 1 to 4 carbon atoms), or R22- or R23C0 -0-CHR24-based hydrazone (where R22 to R24 are as defined above) * and II ζβ represents a nucleophilic leaving group such as a halogen atom or a sulfonic acid ester, i. Tosylsulfonyloxy. The reaction is preferably in a solvent such as digasmethane, tetrahydrofuran, dioxane, dimethylmethylene or dimethyl methyl ether amine, optionally in the presence of a reaction accelerator such as sodium iodide or potassium iodide, and more preferably Preferably in the presence of a base such as sodium carbonate, potassium carbonate or sodium argon solution or in a tertiary organic · base such as N-ethyldiisopropylamine or N-methylmorpholine, which can be used simultaneously as a solvent, It is carried out in the presence, or optionally in the presence of silver carbonate or silver oxide, at a temperature between -30 and 100 ° C, but preferably at a temperature between -10 and 80 ° C. 1) In order to prepare a compound of general formula I, where X: represents a carbonyl group and Υ represents a straight bond C2-4-alkylene, in which case d or d is used. , Or MR. And Rd are substituted with * and the methyl group at the terminal position is replaced with a carbonyl group: The compound of the formula R * — ^ N-Rb (XX) 'ΰ4 (Please read the precautions on the back before filling this page }. Binding-booking ,, ... — 5 0 — Rich paper size + national standard (CNS) T 4 (210X297 mm) 5. Description of the invention (49 A6 B6 Economics. Central Bureau of Standards, Ministry of Economic Affairs Printed by the employee's consumer cooperative (where R and X are "X" means carbonyl U3 or 114-based C 2-4 -ends with terminal radicals such as halogen such as chlorine or bromine). At the temperature of dealkylated diimidazole to 160TC, according to the temperature of its catalytic hydrogen solvent, such as the acid of methyl hydrochloric acid, the above-mentioned, phosphonoamino group or methyl group as defined above * group, one of 圏 represents a hydrogen atom and 113 Or 114-based alkyl, whose M 1 ^ or Rd or methyl group is replaced with Z7-CO-based fluorene, its atom or hydroxyl group, alkoxy group, aryloxy atom or hydroxyl group, methoxy group, ethoxy group In the reaction solution, it is preferably formed in a solvent such as dioxan methane, acetonitrile formamidine or dimethylsulfinium, optionally potassium tributoxide or The H-ethyl diisopropyl water agent such as triphenylphosphine / fluorenazine is carried out at a temperature between -20 and 200 t: The compound of the general formula I obtained by the present invention has a hydrogenated conversion. The corresponding reaction of formula I is preferably M argon, such as Pd / C alcohol, ethanol, ethyl acetate or glacial acetic acid, at a temperature between 0 and 100 ¾, but more, and between 1 and 7 bar *. In the reaction of 3 to 5 bar, any reactivity, methylimidyl group, 0-alkylphosphonic acid group, and aminoimidyl group may be used during the reaction to represent another straight-chain K Rc or Rd. Substituted, and Z7 represents a nucleophilic de- or arylalkoxy group, for example, benzeneoxy or benzyloxy, tetrahydrofuran, toluene in the presence of a base such as sodium hydride, carboamine, or diethyl or N, N′-carbonyl temperature, preferably at 0 unsaturated CC bond, saturated compounds. In the presence of the catalyst, internally, if appropriate, added Rujia at 20 to 60t: hydrogen pressure between. The group such as Traditional protective groups for hydroxyl, carboxyl, alkylamino, and cleavage (Please read the precautions on the back before filling this page)-装 51- China National Standard (CNS) A4 specification (210X297 mm) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. The invention description (50) is protected by K. _. For example, the protective group of the hydroxyl group may be trimethylsilane Group, ethenyl group, benzyl group, third butyl group, triphenylmethyl group, benzyl group or tetrahydropiperanyl group, and the protecting group of carboxyl group may be trimethylsilyl group, methyl group, ethyl group, third group The protective group of butyl, benzyl or tetrahydropiperidinyl group * can be an alkyl group such as methyl, ethyl, isopropyl or n-butyl, phenyl or benzyl, optionally substituted by alkyl The protecting group of the imidyl group may be benzyloxycarbonyl and the protecting group of the amine, alkylamino or imino group may be methylosyl, ethylfluorenyl, trifluoroethylfluorenyl, ethoxycarbonyl, and tert-butyl Oxycarbonyl, benzyloxycarbonyl, benzyl, methoxybenzyl, or 2,4-dimethoxybenzyl, and methyl groups may also be used to protect imine and ft-methyl groups. Kao K-protected amines are also possible. base. The base is optionally cleaved thereafter * For example, hydrolyzable in an aqueous solvent such as water, isopropanol / water, acetic acid / water, tetrahydrofuran / water or dioxane / water, in an acid such as trifluoroacetic acid , In the presence of hydrochloric acid or sulfuric acid or in the presence of alkali scopolamine, such as sodium hydroxide or potassium hydroxide, or with ether cleavage, such as in the presence of iodotrimethylsarane, at a temperature between 0 and 120 t: * It is preferably performed at a temperature between 10 and 100 t :. However, narrower, methoxybenzyl, or benzyloxycarbonyl groups can be cleaved by hydrogenolysis, for example using hydrogen in the presence of a catalyst such as Pd / C in a solvent such as formic acid, ethanol, ethyl acetate, or glacial acetic acid. If appropriate, add an acid such as hydrochloric acid, at a temperature between 0 and 100 Torr • but preferably at a temperature between 20 and 60 t: between 1 and 7 bar, preferably under an argon pressure of 3 to 5 bar. However, 2,4-dimethoxybenzyl is preferably cleaved in trifluoroacetic acid in the presence of methoxybenzene. (Please read the precautions on the back before filling in this page.) I 5 2 — This paper size is in Chinese paper (CNS) 〒 4 specifications (210X297 cm ^ ~ 5. Description of the invention (51) A6 B6 Ministry of Economic Affairs Central Bureau of Standards X. Consumer cooperatives print third-butyl or third-butoxy acid treatment, or κ-iodotriethylsilyl dimethane, dioxane, methyltrifluoroethyl ether, preferably M such as or In the solvent of formazan, treat with 50 to sodium oxide solution * Depending on the situation, the amine group is cleaved from methyl-methylimine group in the presence of 1-chloroethyl formic acid at a temperature between 0 and 50 t:- In the presence of naphthalene, in a solvent such as or dioxane, an alcohol between 20¾ to the boiling temperature of the reaction solution, at 201: to the boiling of the alcohol, the fluorenyl group is preferably in the presence of hydrazine or a solvent such as Methanol, six cycles, between 20 and 50 t: only one alkyl group from 0,0 potassium dichloride, in a solvent such as acetone, ethyl, at a temperature between 40 and 150 t. The temperature of 2 alkyl radicals is from dialkylethylsilane, bromotriethylsilane such as dichloromethane, chloroform or acetonitrile, but preferably between 20 and 120 ° C. Such as tetrahydrolysis. The solution is preferably * preferably a diamine with a temperature between 0 and 150 ° C in dichloromethane, such as methyl ethyl fermentation, and a degree of cleavage of alkylphosphonic acid methyl ketone at different temperatures, but is higher than that of phosphonium phosphonate or chlorotriethyl. Within 0 6 Ot: between the K-acid such as trifluoroacetic acid or salt hydrolysis • optionally use a cocoon such as 0 treatment, and optionally cleave at a temperature such as acetic acid * or in a solvent of hydrogen furan or methanol, in 1-Chloroalkyl is carried out at a temperature such as 1, 8-, 1,2-dichloro, and the cleavage of amine, ethylamine or propanol, and the tolyl group at the same temperature is better than that of acetonitrile or dijia. Iodine methylformamide 1 is preferably used at 60 to about formic acid esters such as bis- (dimethylethane, toluene, preferably at the end, such as methanol, n-butylamine / water, or dioxane. The cleavage between π, for example, M iodotriyl silane / sodium iodide is carried out at a temperature between the solvent and the boiling temperature of the reaction solution ... ........................................ ........... install ..................... ........, {Please read the notes on the back before filling out this page} 53 Dimensions: China National Standards (CNS) 4 specifications (210x297 mm) Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs · A6 B6 V. Description of the invention (52) Furthermore • The compound of general formula I obtained can be as above It can be resolved into its isomers and / or non-image isomers. Therefore, for example, a cis / trans mixture can be resolved into its cis or trans isomer, and a compound having at least one optically active carbon atom can be resolved. Resolution to mirror isomers. Therefore, the obtained cis / trans mixture can be resolved by K chromatography to obtain its cis and trans isomers and the racemic form of the compound of the general formula I can be well-known methods (see Allinger HL and Eli .el EL was isolated from "Topics in Stereochemistry", Volume 6 »Wiley Interscience, 1971) into its optically mirrored isomers, and the compounds of general formula I with at least 2 asymmetric carbon atoms may differ in their physical chemistry A known method, such as M chromatography and / or fractional crystallization, is used to separate the non-mirromeric isomers, which, if in racemic form, can be separated into the mirror isomers as described above. Mirror isomers Phase column separation or recrystallization from optically active solvents, or K reacts more effectively with optically active substances, especially acids or their activated derivatives or alcohols, which form salts or derivatives with racemic compounds such as esters or fungi. The amine is then separated and the non-mirromeric salt mixture or derivative thus obtained is, for example, based on its different solubility, however, free-running mirror image isomers can be released from pure non-mirroimage isomers by suitable reagents. Particularly commonly used optically active acids include, for example, tartaric acid and dibenzyl tartaric acid in the D- and L-forms, di-o-solanyl tartaric acid, malic acid, phenylglycolic acid, camphorsulfonic acid, glutamic acid, asparagine Tart or cinchona acid. Examples of optically active alcohols include (+) or examples of optically active fluorenyl groups in menthol and amidine include (+) or (-)-fluorenyloxycarbonyl. —5 4 — This paper size is tsa home standard (CNS) A4 size (210x297 mm) ............... ........................................ ............... ^ ............................ ΤΓ ............. ........... $ (Please read the notes on the back before filling in this page) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A6 _ B6_ V. Description of the Invention (53) — Furthermore, The resulting compounds of formula I can be converted into their salts *, especially for road medicine use and inorganic or organic acids into their physiologically acceptable salts. Examples of suitable acids include hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, fumaric acid, succinic acid, lactic acid, citric acid, tartaric acid or maleic acid. In addition, the new compound of formula I thus obtained, if it has a carboxyl group, a sulfonic acid group, a phosphonic acid group, a 0-alkylphosphonic acid group, or a tetrazol-5-yl group, can be subsequently reacted with Or organic acids are converted into their addition salts, more particularly as K-medicine uses, into their physiologically acceptable salts. Examples of suitable bases include sodium hydroxide, potassium hydroxide, arginine, cyclohexylamine, ethanolamine, diethylenamine, and triethanolamine. The compounds as starting materials are in some cases known from the literature or can be prepared by methods known from the literature (see Examples). So * For example, the preparation of corresponding triazole compounds is described in " The Organic Chemistry of Heterocyclic Compounds' *, Volume 3.7, C. Temple Jr., John Wiley & Sons, 1981, Chapters 13, 14, and 19 ° The preparation of corresponding cyclic urea compounds is described in Houben-Weyl, " Methoden.der Organischen Chenie ", Volume E4 Η Hagemann, Georg Thieme. Verlag, 1983, p. 368. Also, in the same volume, an example method describing the preparation of a corresponding open bond gland compound that may require a starting compound starts on page 355. Therefore, for example, the corresponding cyclic gland derivative is cyclized to the corresponding substituted gland (which is sequentially prepared by reacting the corresponding amine with the corresponding isocyanate) * or K is to replace the corresponding substituted diamine with, for example, a dioxocarbonyl Carbonic acid derivative reaction system—5 5 _ This paper is scaled to the Chinese National Standard (CNS) ▼ 4 specifications (210 × 297 mm) ......... ........-............................ ... installation ......... may ... ............ Comprehensive (please read the notes on the back before filling in this page) Printed by A6 B6, Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (54), or corresponding dihydrogen Triazolone derivatives are prepared by cyclizing the corresponding hemicarbazide, which is sequentially prepared by reacting the corresponding isocyanate with the corresponding hydrazine. In the cyclic gland derivative thus obtained, if necessary, a carbonyl group can thereafter be converted into a corresponding thiocarbonyl or carbimide group by a known method. In the resulting cyclic starting material or in the preparation of such starting materials on demand, any ester group present can be hydrolyzed to convert to a carboxyl group or any existing carboxyl group can be converted to an ester group. As mentioned before, the novel cyclic derivatives of the general formula I and their addition salts • particularly their physiologically acceptable addition salts with no hydrazone or organic acid or hydrazone have important characteristics. Therefore, the compounds of the general formula I have important pharmacological properties and, in addition to their anti-inflammatory and bone-degrading effects, they particularly have anti-coagulant, anti-aggregation and tumor or metastatic inhibitory effects. By way of example, the biological effect of the compound of general formula I has been discussed as follows: 1. Manufactured 3Η-ΒΤΒΗ 52 combined with suspension of human Ifa claw f. Human platelet suspension in plasma and 3H-BIBU 52 [two (3 $, 53) -5-[(4'-methylimidyl-4-biphenyl) oxymethyl] -3-[(carboxy) methyl] -2-pyrrolidone [3-3 hydrazone-4-biphenyl] ] A culture, its replacement from the literature (see German patent application P 42 14 245.8, filed by the same applicant on April 30, 1992, internal reference code: case number 5 / 1093-FL > known coordination 12SI-fibrinogen and different concentrations of test substance. Free and bound ligand M is centrifuged and determined by flash count. The SH_BIBlj 52 binding caused by the test substance is determined from the obtained measurement value. In order to perform this test, the donor blood was drawn from the reverse elbow vein and citric acid—56 was used. This paper is scaled to the size of China National Knead (CDS) A 4 (210X297 mm) {Please read the back first Please note this page before filling in). Packing .. 3J +. A6 B6 V. Description of the invention (55) Three nanometers (final concentration of 13 millirales) anti-coagulation. The blood was centrifuged at 170 x g for 10 minutes and the supernatant platelet concentration plasma (PRP) was removed. The remaining blood was centrifuged again to recover the plasma. P R P K autologous plasma was diluted 1:10. 750 μl with 50 μl saline, 100 μl test substance solution, 50 μl 14C-sucrose (3700 Bq) and 50 μl 3H-BIBU 52 (final concentration 5 nanomolar) at room temperature Incubate for 20 minutes. For the determination of non-specific binding * 5 μl of BIBU 52 (final concentration 30 μM) was used instead of the test substance. The samples were centrifuged at 10,000 X s for 20 seconds and the supernatant was aspirated. Its 100 microliters were determined to determine the motif of the moult. The pellet was dissolved in 500 microliters of 0.2 equivalent NaOH, 450 microliters were mixed with 2 ml of scintillator and 25 microliters of 5 equivalent HC1 and measured. The residual plasma in Yuyu in the film was determined from 14C-containing, and the binding ligand was determined from 3H-measured value. After subtracting non-specific binding, the pellet activity is plotted against the test substance concentration and the 50! «Binding inhibition concentration is determined. 2. Anticoagulant rfii method 柹 Method Platelet aggregation was determined by Bor η · Cross method (J. Physiol. 170: 397 (1964)) in platelet-derived thick blood plasma extracted from healthy volunteers. In order to inhibit aggregation, the blood was mixed with a volume ratio of 3.14 ¾ sodium citrate 1:10. Decrease in optical density of platelet suspensions of G. sibiricum L. polysaccharides was measured and recorded photometrically after the addition of aggregation-initiating substances. The aggregation rate is determined by the inclination angle of the density curve. The point of maximum light penetration on the curve is used to calculate the optical density. -57- Used in this paper standard AA standard (CNS) A4 size (210X 297 mm) t Please read the precautions on the back before filling in this page}. Binding. Binding. Staff of the Central Bureau of Standards, Ministry of Economic Affairs Printed by the consumer cooperative A6 __B6___ 5. Description of the invention (56) The amount of gelatin is only as small as possible, but it is enough to produce an irreversible response curve. The standard gelatin product used was from Hormonche in Munich. Before the gelatin was added * the plasma and the test substance were incubated at 37 t for 10 minutes. From the obtained measured values, ECB0 is determined graphically, that is, a change in M aggregation inhibition in terms of optical density by 50 °. The following table contains the results obtained: (Please read the notes on the back before filling in this page} Substances printed by Shellfish Consumer Cooperatives, Central Bureau of Standards, Ministry of Economic Affairs (Example No.) 3H-BIBU 52-Binding Test IC5〇 [ nM] ECB inhibition of platelet aggregation. [nM] 1 190 > 10000 2 (1) 5400 > 10000 2 (2) 24 40 6 110 40 8 (1) 36 150 9 85 190 9 (1) 760 gg〇19 59 230 19 (1) 120 350 19 (3) 81 430. Packing_ 5 8 — This paper size is not applicable to the national standard (CNS) A4 specification (210X297 public love) A6 B6 V. Description of the invention (57) (Please read the precautions on the reverse side before filling out this page) Furthermore, the compounds of Examples 7 and 19, for example, were administered orally and ocularly at 1 mg / kg * to inhibit gelatin-induced platelet aggregation in Rhesus monkeys, respectively. At 5 and more than 8 hours. The compound according to the present invention is tolerable * because after intravenous injection of 30 mg / kg of the compound of Examples (8) 1 and 19 to 3 mice · 3 test animals did not have Death. Depending on its inhibitory effect on cell-cell and cell-matrix interactions * New cyclic gland derivatives of general formula I and their growth The above-acceptable addition salts are suitable for combating or preventing diseases in which smaller or larger cell aggregates occur or diseases in which cell-matrix interactions play a part, such as to treat or prevent venous and arterial embolism, the brain Vascular disease, pulmonary embolism, cardiac embolism, arteriosclerosis, osteoporosis, and tumor metastasis and treatment are caused by free passage between cells or the interaction between cells and solid structures, or acquired disorders. It is also suitable for the treatment of vitamin Decomposers or vascular insertion methods such as concurrent treatment of vascular germ cells for thrombolysis or concurrent treatment for shock, dry addiction, diabetes and inflammation. To treat or prevent the above diseases, the dosage is 0.1 microgram to 30 Between mg / kg of body weight, preferably between 1 microgram and 15 mg / kg of body weight, and is administered to 4 daily doses. For this purpose, the compounds of formula I produced according to the invention, as appropriate, with other active substances such as Prostaglandin cell receptor inhibitors and prostaglandin synthesis inhibitors or combinations thereof, 5-hydroxytryptamine antagonists, alpha-receptor antagonists, alkyl nitrates Esters such as glycerol trinitrate, phosphodiester sea inhibitors, prostacyclin and its analogs, fibrinolytic agents such as tPA, prourokinase, urokinase, streptokinase or anticoagulants such as liver — 5 9 — this paper When the ruler is 8 Η Home materials (where) T4 wire (210X297 mm) A6 B6

V. Description of the invention (58) Glucotin, pitroxin sulfate, clotting sea or one or more of its inert traditions, sucrose, microcrystalline fibric acid, tartaric acid, water / polyethylene glycol, acryl such as hard wax or its combination (galenic ) Formulations, solutions, and sprays of Example g oil {Example T, Activated protein C, Vitamin K antagonist, Inhibitor of hydration activating coagulation factor, can be combined with 1 carrier and / or diluent, such as Corn starch, lactose vitamins, magnesium stearate, polyvinylpyrrolidine, citrate-like, water / ethanol, water / glycerin, water / sorbitan, dihydratase, stearyl alcohol, carboxymethyl retinoin or fatty A suitable blend · Incorporates into traditional galens such as regular and coated tablets, capsules, powders, suspensions or suppositories. It is to explain the present invention: (谙 Please read the notes on the back before filling in this page)-Install the Central Standards Bureau of the Ministry of Economic Affairs 1-(Although dark 瞅 -H-argon-fi-some methyl argon some 雔 some 1 -cage 2.6 grams of 1- (isoquinolin-6-yl) -3- [4- [2- (methoxycarbonyl) ethyl] -phenyl] -tetrahydropyrene The oxazol-2-one M was heated and dissolved in 175 ml of dichloromethane. The mixture was cooled in an ice bath and mixed with 1.46 g of 3-chloroperoxy stearic acid (90¾ strength). After stirring at 0 t for 24 hours, the mixture was stirred. Diluted with M dichloromethane and extracted twice with M sodium bicarbonate and sodium thiosulfate solution, followed by K water extraction. The organic layer was separated, dehydrated and evaporated. Yield: 2.4 g (88¾ of theory) Value: 0.15 (silicone) ; Dichloromethane / methanol / ethyl acetate = 20: 1: 1) 例 Examples TT N- (2- 锊, 乙, 某) -H '-(Isophospholine-fi- 某) -H- 「4- "2-f Tian argon even forging 60 This paper size is applicable to country B family standard (CNS) A4 specifications (210X 297 mm). Order_

I Printed by A6 B6, Shellfish Consumer Cooperatives, Central Standards Bureau, Ministry of Economic Affairs 5. Description of Invention (59) A) B, 1, Rong, 1-urea in 7.2 g of imidazole and 10.1 g of N, N'-carbonyldiimidazole in 1 In 0 ml of dimethyl sugar amine • Add 9.0 g of 6-aminoisoquinoline to 70 ml of dimethylformamide at 0 to 10 t! Dropwise. After stirring for 2 hours at room temperature * 15.3 g of H- (2-hydroxyethyl 4- [2- (methoxycarbonyl) ethyl] -benzylamine was added dropwise and the mixture was stirred at room temperature for 2- 1/2 day. The mixture was diluted with 750 ml of ethyl acetate and extracted twice with M water and saturated brine. The layer was separated, dehydrated, and evaporated. The residue was decanted in a silica gel column using ethyl acetate / Di atmospheric methane / methylbenzene = 70:30:10 purification. Yield: 4.8 grams (19HO of theoretical value,

Ri · value: 0.48 (silicone; dichloromethane / methanol / ethyl acetate = 20: 1: 1) The following compounds were prepared from analogous to Example II: (1) 1- (2,2-diethoxyethyl ) -1 <,-(isoquinolin-6-yl) -1 <-[4- [2- (methoxycarbonyl) ethyl] phenyl] -gland

Rf value; 0.50 (silicone; dichloromethane / methanol = 20: 1) (2) N- (3-ethyl-2,3,4,5-tetrahydro-111-3-benzo-nitrozine seven- 7-yl) 4 '-(2,2-diethoxyethyl)-^ ('-[trans-4- [2- (methoxycarbonyl) ethyl] -cyclohexyl] -gland melting point: 101 -104 υ

Rf value: 0.63 (silicone; methane / methanol / concentrated aqueous ammonia = 90: 10: 2) (3) 11- (7-ethyl-6,7,8,9-tetrahydro-511-pyridine -[2,3-〇1] -azaheptazone-2-yl) -N '-(2,2-diethoxyethyl) -M'-[trans-4- [2- (methoxy- 61 — Prestige: _... this paper. Zhang Zhiyuan uses the Chinese National Standard (CNS) A4 size (210X297 mm) ... .......................... ii ....... ..................... TΓ ............. ........, (Please read the notes on the back before filling in this page} A6 B6 Member of the Central Standards Bureau of the Ministry of Economic Affairs ΗPrinted by Consumer Cooperatives V. Description of the Invention (60 carbonylcarbonyl) ethyl] -ring Hexyl] -gland with 1,1'- and 1,1'-carbonyl-di- (1,2,4-triple beer) Melting point: 100-102 t: Value: 0.41 (silicone; dichloromethane / methanol = 9: 1) Theoretical value: C 62.40 Η 8.73 Ν 13.48 Found value: 62.19 8.79 13.62 (4) ^ 1- (7-benzyl-6,7,8,9-tetrahydro-511-pyrimido- [4 , 5-0] -azahepta-2-yl) -1 < '-(2,2-diethoxyethyl)-^'-[trans-4- [2- (methoxycarbonyl)- Ethyl] -cyclohexyl] -glandular fused with 1,1'-carbonyl-di- (1,2,4-triazole) Value: 0.23 (reverse-phase silicone; methanol / 5¾ saline solution = 6: 4) Fenton's example TTT material-(3- flute ~ butyl argon forging a certain-? .. 3.4.5-tetra argon -114-:?-荣 # 一气 十 照 -7-a) -M- (2-a certain a second) -N'-U- "2- (Shen arg a certain carbonyl a) A a certain 1-cage a 1- 腩 克 3- ( Third butoxycarbonyl) -7-[(2-hydroxyethyl) amino] -2,3,4,5-tetrahydro-111-3-benzodiazepine and 3.7 g of 4- [2 -(Methoxycarbonyl) ethyl] -benzyl-isocyanate (prepared from the reaction of the corresponding amine M with carbonyl dichloride) was stirred in 35 ml of dioxane at room temperature for 3.5 hours. The reaction solution was evaporated and the residue was M tertiary butyl methyl ether is mashed and evacuated. The product K tertiary butyl methyl ether is washed and dried. Yield: 6.3 g (76¾ of theory) Melting point: 11 5 -117 C, Rf: 0.30 (silicone; ring Hexane / ethyl acetate = 1: 1) (Please read the precautions on the back before filling in this page)-Binding. -62- This paper ϋ uses national standard (CNS) A4 size (210X297 mm) ) " V. Explanation of the invention (61) The compound was prepared from Example 111 similar to: (1) Buethenyl-4- [4- [2- (methoxycarbonyl) ethyl) phenyl ] -Half Card Hydrazine (ethylglycosylhydrazine and 4- [2- (methoxycarbonyl) -ethyl] -phenyl isocyanate vinegar 0 Melting point: 159-165χ

Rr value: 0.37 (silicone; methane / methanol = 9: 1) (2) N- (2-hydroxyethyl) -N- [trans-4- [2- (methoxycarbonyl) ethyl)- Cycloethyl]-^-(3-trifluoroethylfluorenyl-2,3,4,5-tetrahydro-111-3-benzotriazine-7-yl) -gland Melting point: 15 0-15 2/0,

Rf: 0.31 (silicone; cyclohexane / ethyl acetate = 1: 1) (3) N- (2,2-diethoxyethyl) -N- (3-trifluoroethylfluorenyl-2,3 , 4,5-tetrahydro-lH-3-benzylazine-7-yl)-^ Γ- [trans-4- [2- (methoxycarbonyl) -ethyl] -cycloethyl] -[Trans-4- [2- (methoxycarbonyl) ethyl] cycloethyl] -isocyanate used in glands is prepared by reacting the corresponding amine hydrogen chloride K with carbonyl dichloride. 7-[(2,2-diethoxyethyl) amino] -3-trifluoroethylfluorenyl-2,3,4,5-tetrahydro-1H-3-benzomonoazine [Rf: 0.76 (silicone; cyclohexane / ethyl acetate = 3: 2)] M7 -amino-3 -trifluoroacetamido-2,3,4,5-tetrahydro-1 [1 -3- Benzoazine groups are prepared by reacting bromoacetaldehyde diethyl acetal in the presence of N-ethyldiisopropylamine. Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling in this page)

Rf: 0.26 (silicone; cyclohexane / ethyl acetate = 3: 2) (4) N- [trans-[[((methoxycarbonyl) methyl] oxy] cycloethyl] -K '-(2, 2-diethoxyethyl) -11 '-(3-trifluoroethylfluorenyl-2,3,4,5-tetrahydro-1 {1-3-benzene-63- National Standard (CNS) A4 Specification (210X297mm) Printed by A6 B6, Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the Invention (62) Zirconium Seven Park-7-based)-used by the gland [anti- 4-[[(methoxycarbonyl) methyl] oxy] cycloethyl] -isocyanate is prepared by reacting the corresponding amine hydrogen chloride M with a dicarbonylated carbonyl.

Rr: 0.20 (silicone; cyclohexane / ethyl acetate = 1: 1) (5) N- (2-hydroxyethyl) -N- [4- [trans-2- (methoxycarbonyl)- Ethyl] phenyl] -N ·-(3-trifluoroethynyl-2,3,4,5-tetrahydro-111-3-benzo-nitroazine-7-yl) -gland (3-Trifluoroethylfluorenyl-2,3,4,5-tetrahydro-1fluorene-1benzo-3-azine-7-yl) -isocyanate is prepared from the corresponding amine by reaction with carbonyl dicarbonyl Melting point: from 118t:

Rf: 0,18 (silicone; cyclohexane / ethyl acetate = 1: 1) (6) 1 [4- (2- (ethoxycarbonyl) -1-propyl] phenyl]-^-(2 , 2-diethoxyethyl) -N '-(3-trifluoroethylfluorenyl-2,3,4,5-tetrahydro-1H-3-benzylazine-7-yl)- The corresponding [4- [2- (ethoxycarbonyl) -propyl] phenyl] -isocyanate M used by the gland is prepared by reacting the corresponding amine with carbonyl dichloride.: 0.35 (silicone; cyclohexane / ethyl acetate = 2: 1) (7) [trans-4- [2- (methoxycarbonyl) ethyl] cyclohexyl] -N '-[(benzyloxycarbonyl) methyl] -N'- (3-trifluoroacetamidine -2,3,4,5-tetrahydro-1H-3 -benzo-nitroazine-7-yl) -urea 7-[[(benzyloxycarbonyl) methyl] amino] -3 -Trifluoroethylfluorenyl-2,3,4,5-tetrahydro-111-3-benzomonoazine seven groups [1 ^ value: 0.24 (silicone; cyclohexane / ethyl acetate = 4: 1)] Μ7-amino-3-trifluoroacetamido-64_ This paper is standard for the national standard (CNS) A4 (210X297 mm) ............... ........................................ ....-......... Equipment ............ Order ... ......, (Please read the notes on the back before filling in this page) Printed by A6 B6, Consumer Cooperatives of the Associate Bureau. 5. Description of the Invention (63) -2,3,4,5-tetrahydro-1H-3-benzodiazepine and benzyl bromoacetate in N-ethyldiiso Prepared by reaction in the presence of propylamine.: 0.51 (silicone; cyclohexane / ethyl acetate = 1: 1) (8) N- (3-hydroxypropyl) -N- [trans-4- [2- ( (Methoxycarbonyl) ethyl] cyclohexyl]-^ '-(3-trifluoroethylfluorenyl-2,3,4,5-tetrahydro-111-3-benzylazine-7-yl) -Gland melting point: 129-130¾ (9) 1-Ethylfluorenyl-4- [trans-4- [2- (methoxycarbonyl) ethyl] -cyclohexyl] -hemicarbazine Melting point: 176-179 ¾ Value : 0.24 (silicone; digas methane / methanol = 95: 5) (10) 1-methylfluorenyl-4- [trans-4- [2- (methoxycarbonyl) ethyl] -cyclohexyl] -half card Hydrazine Melting point: 169-1711: (11) N- [4- [2- (ethoxycarbonyl) -1-phenyl-ethyl] phenyl] -N '-(2,2-diethoxyethyl ) -N'- (3-trifluoroethylfluorenyl-2,3,4,5-tetrahydro-1H-3-benzo-azaazine-7-yl) -gland [4- [2 -(Ethoxycarbonyl) -phenylphenyl-ethyl] phenyl] -isocyanate is prepared by reacting the corresponding amine M with carbonyl dichloride. The crude product was used directly to prepare the compound of Example 5 (6). (12) Carboxamyl-4- (3-trifluoroethenyl-2,3,4,5-tetrahydro-1) 1-3-benzo-nitroazine-7-yl) -half card Hydrazine

Rf value: 0.41 (silicone; dichloromethane / methanol = 9: 1)

Example TV-1 65 — This bismuth sheet scale uses the Chinese National Standard (CNS) T4 specification (210X297 mm) ............. ........................................: i ........ ..................... TΓ ............. ........ ^ (Please read the notes on the back first, then Qiwo on this page) B6 V. Description of the invention (64) 3-(Di Sanchi gas carbonyl even) -7-"（2- 经A certain a) amine 1-2.3.4 · 5-tetrathine 1 1 H-3-cage # 7.2 g 7-amino-3- (third butoxycarbonyl) -2,3, 4,5-tetrahydro-lH-3-benzyl-nitrogen seven paintings (from 7-nitro-2,3,4,5-tetrahydro-lH-3-benzo-nitrozine seven plaques and dicarbonate Tributyl ester reaction and subsequent hydrogenation in the presence of Pcl / C) Prepared in 130 ml of methanol with 1.53 ml of glacial acetic acid and 1.8 g of glyoxal (dimer). Then add 1.9 g of sodium hydroborate And the mixture was stirred at room temperature for 1 hour. The reaction solution was evaporated and the residue was separated between ethyl acetate and water. The organic solution was washed twice, washed with K water twice, dehydrated and evaporated. The residue was decanted on a silica gel column. Purified with cyclohexane / ethyl acetate (4: 6). Amount: 5.4 g (64¾ theoretical value), mp: 86-891:

Rf value: 0.39 (silicone; cyclohexane / acetic acid acetate = 4: 6) The following compounds were prepared from analogous to Example IV: (1) trans-4-[(2-hydroxyethyl) amino] -cinnamate Ester melting point: 117-118¾

Rf value: 0.25 (silicone; cyclohexane / ethyl acetate = 1: 1)

SJii_MJL L4aRS ^ _6RS. 8aRS)-6- Γ C2.2-— g arg y y y y y y y 1-2-Tian * -1.2.3.4.4a. S.fi.7Ua- + M Session of the Ministry of Economic Affairs Printed by the Consumer Standards Cooperative of the Central Bureau of Standards (please read the precautions on the back before filling this page) at 9,0 g (4aRS, 8aRS) -2-methyl-6-oxyl-l, 2,3,4, 4a, 5,6,7,8,8a-decahydroisopyridine and 6.8 g of aminoacetaldehyde dimethyl acetal in 90 ml of acetonitrile, 31 ml of 3 equivalent hydrochloric acid was added and the mixture was at 66 This paper uses the standard Chinese National Standards for Difficulties (CNS) T4 (210x297 mm). 5. Description of the invention (65) Stir at room temperature for 30 minutes. It was then cooled in an ice bath and 4.4 g of sodium cyanoborohydride was added in portions. After stirring at room temperature for 30 minutes and standing overnight, the mixture was evaporated, diluted with ice water and adjusted to a pH of 10-11. The mixture was extracted three times with ethyl acetate. The ethyl acetate extract M saturated saline solution was washed twice, dehydrated and evaporated. The residue M was purified on an alumina column (basic). Yield: 7.35 grams (53¾ of theory)

Rr value: 0.25 (alumina, ethyl acetate) (1) (4aRS, 6RS, 8aRS) -6-[(2,2-dimethoxyethyl) amino] -2-methyl-1,2 , 3,4,4a, 5,6,7,8,8a-decahydroisoquinoline M by-product of Example V was isolated.

Rf value: 0.56 (alumina, ethyl acetate)

Example of VT 7-Touch-3- =. Argon 7, 2.3-4.5-Four 氲 1 1 卩 -3- Cage # 1 氲 10 Circles Read the notes on the back and fill in this page) 2.6 g of 7-amino-3-trifluoroacetamido-2,3,4,5-tetra-argon-1 [1-3-benzyl-nitrozine Fifty milliliters of 103! Hydrochloric acid was heated with brief stirring, then cooled to 0 t! And 695 mg of sodium nitrite was added dropwise under 0 t: and further cooling to 14 l of water. At 0 t: 1.7 g of potassium iodide and 1.3 g of a solution and a mixture of 10 g of the solution were added dropwise and stirred overnight at room temperature. The upper layer was then poured and the resulting residue was dissolved in dichloromethane. It has a calendar with sodium bisulfite solution and water for washing, brooding, dehydration, filtration and evaporation. The crude product was purified by chromatography on a silica gel column with cyclohexane / ethyl acetate (4: 1). Yield: 2.4 grams (65¾ of theoretical value), Melting point: 80-82t: -67-This paper size uses China B National Standard (CNS) A4 specifications (210X297 mm). Cooperative printed A6 _ B6 V. Description of invention (66)

I value: 0.61 (silicone; cyclohexane / ethyl acetate = 4: 1) g Example V 丨 T 7 -Amine = Confucian 7, Yunmou-2.H5 -Tetrahydro-1H-3-cage # One Portuguese ten

I 3 g of 7-nitro-3-trifluoroethylfluorenyl-2,3,4,5-tetrahydro-l-fluorene-benzo-nitrazine in 200 ml of ethyl acetate κ3 g 10 »! Pd / C was hydrogenated at room temperature under 50 pSi hydrogenation for 1 hour. The catalyst is removed by suction filtration and the liquid is evaporated. The residue is heated with tertiary butyl methyl ether and then cooled and then filtered through suction, washed with tertiary butyl methyl ether and dried. Yield: 12.2 g (79¾ of theory), Melting point: 102-104¾

Rf value: 0.31 (silicone; cyclohexane / ethyl acetate = 2: 1) The compound under K was prepared similarly to Example VII: (1) 7-amino-3-tert-butoxycarbonyl-2,3 , 3,3-butoxycarbonyl-7-nitro-2,3,4,5- & hydro-111-3 -Benzomonoazine with 7-nitro-2,3,4,5-tetrahydro-111_3-benzodiazepine-Paper-hydrogenated compound with di-tert-butyl pyrocarbonate Prepared by reaction in the presence.

Rr value: 0.40 (silicone; cyclohexane / ethyl acetate = 7: 3) (2) 7-limyl-3-ethyl-2,3,4,5-tetrahydro-1H-3-benzyl Nitrogen group M Raney nickel is carried out in formazan. Value: 0.50 (Silicone: Toluene / Dioxane / Methanol / Port® Water. = 20: 50: 20: 3) —δ 8 — This paper uses the national standard (CNS) f 4 specifications ( 210X2974 ^ ...................................... ............ Binding ........ Outline < Please read the notes on the back before filling in this page} '' Ministry of Economy Printed by A6 B6, Shellfish Consumer Cooperative of the Central Bureau of Standards 5. Description of the invention (67) (3) 3- (4-Aminophenyl) -3-phenylpropionic acid ethyl alcohol hydrogenated in ethyl acetate It is carried out in the presence of hydrochloric acid. Starting material 3- (4-nitrophenyl) -3-phenylethyl acrylate [value: 0.36 (silicone; cyclohexane / dichloromethane = 1: 1)] M 4- Prepared by reaction of nitrodiphenylphosphonium with triethylphosphonoacetic acid. Value: 0.40 (reverse phase silicone; formazan / 5¾ saline solution = 6: 4)

Fen Lili VT TT 7-nitrate-3 = Μ7 · cat certain -m 5 -tetra-M-1 5-tetrahydro-1H-3-benzo-nitrogen seven [Rf value: 0.76 (silicone; cyclohexane / ethyl acetate = 1: 1), its M 2,3,4,5-tetrahydro-1H -3-Benzanitazine and trigas acetic anhydride prepared in the presence of N-ethyldiisopropylamine] in 60 ml of concentrated sulfuric acid, 0 to 8 TC, dropwise within 1.5 hours Add a mixture of 9.7 g of potassium nitrate and 50 ml of concentrated sulfuric acid. The mixture was warmed to room temperature, poured into 1 liter of ice * and extracted with ethyl acetate. Ethyl acetate extract M water and washed with saturated saline solution, dehydrated and evaporated. The residue was heated with tertiary butyl methyl ether. It was then cooled and the product was filtered with suction and washed with M tert-butyl methyl ether. Yield: 16.2 g (59¾ of theory), Melting point: 116-119 Ό

Rr value: 0.57 (silicone; cyclohexane / ethyl acetate = 2: 1) The compound under K was prepared similarly to Example VIII: (1) 7-nitro-2,3,4,5-tetrahydro-1H -3-Benzo-nitrogen heptahedral-hydrogen atmosphere-69- This paper size is in accordance with China National Standard (CNS) A4 (210X297 mm) .............. ........................................ ........... installation ............ may ... ....... Korean {Please read the notes on the back. Then fill in this page} Printed by A6 __B6_ of the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 68) The reaction was performed with sulphuric acid / potassium nitrate and K hydrogen was separated. Melting point: 235-238 t: (decomposition) Theoretical value: C 52.52 Η 5.74 N 12.25 Cl 15.50 Experimental value: 52.44 5.80 12.07 15.36

Jing Li TX 4- "4-" 2- (Shen Xihua Huamou) 7, some 1 cage some 1-5- Tianmian-/ ^-1.2.4- two poor one-post-3 _ Seoul 8.1 1-Z > fluorenyl-4- [4- [2- (methoxycarbonyl) ethyl] -phenyl] -hemicarbazide and 60 ml of a 1-equivalent makoto sodium hydroxide solution were heated in a steam bath for 1.5 hours. The mixture was then cooled, filtered, and the filtrate was slightly acidified with citric acid. It was filtered and the filtrate was combined with concentrated hydrochloric acid. The precipitate was filtered, washed with water, and dehydrated. The intermediate was mixed with some methanolic hydrochloric acid in formic fermentation. Night. The reaction solution was evaporated and the residue was mashed with tertiary butyl methyl ether, evacuated »and dried. Yield: 4.98 g (65¾ of theory), value: 0.40 (silicone; methylbenzyl ether / dioxane / Ethanol / glacial acetic acid = 90: 10: 10: 6) Theoretical value: C 59.76 Η 5.79 Η 16.08 Experimental value: 59.54 5.86 16.05 The compound on K is prepared similarly to Example IX: (1) 4- [Trans-4- [ 2- (methoxycarbonyl) ethyl] cyclohexyl] -5-methyl-4Η -1,2,4-dihydrotriazole-3-_ Melting point: 179-181¾ -70 — For paper size National Standards for Difficulties (CNS) T.4 (210x297 mm) < Please read the notes on the back first Fill in this page). Binding and binding. Printed by A6 B6__ of the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs. 5. Description of the invention (69) (2) 4- [trans-4- [2- (methoxycarbonyl) ethyl ] Cyclohexyl] -4H-1,2,4-dihydrotriazol-3-one Melting point: 142-144 * 0 (3) 4- (3-Third-butoxycarbonyl-2,3,4,5 -Tetrahydro-111-3-benzomonoazine-7-yl) -4fluorene-1,2,4-dihydrotriazol-3-one starting compound: the compound intermediate of Example III (12) Reacts with di- and di-butyric pyrocarbonate instead of formic acid. Melting point: 185-186¾

Rf value: 0.25 (silicone; cyclohexane / ethyl acetate = 2: 3)

Example X K- "trans (field argon sugar) ethyl 1 1R R 1-7, 5.0 g N-benzyl-N- [trans-4- [2- (methoxycarbonyl ) Ethyl] cyclohexyl] -ethanolamine in 150 liters of methanol M1.0 g of 10! K Pd / C hydrogenated at 50 t and 50 pS i pressure for 1-3/4 hours. The mixture was filtered and evaporated Yield: 3.3 g (9250 of theoretical value: 0.20 (silica gel; dichloromethane / methanol / concentrated ammonia = 9: 1: 0.4) The compound under K was prepared similarly to Example X: (1) (trans-4- Aminocyclohexyl) tert-butyloxyacetate [trans- (4-dibenzylamino) cyclohexyl] -tert-butyloxyacetate [value: 0.51; (silicone; cyclohexane / ethyl acetate) Ester = 4: 1)] M trans-4- (dibenzylamino) -cyclohexanol and tert-butyl bromoacetate in toluene / 50 * trioxide solution in the presence of tetrabutylammonium hydrogen acetate Prepared by the following reaction: 1 value: 0.56 (reverse phase silica gel; methanol / 5¾ saline solution = 6: 4). -71- This paper size is in accordance with China National Standard (CNS) A4 specification (210X297 mm) '{Please Read the notes on the back before filling in this page). Packing: • Order.-Silk. Printed by A6 B6__, the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs Explanation (7C)) (2> H- (3-hydroxypropyl) -N- [trans-4- [2- (methoxycarbonyl) -ethyl] cyclohexyl] -amine

Rf value: 0.10 (silicone; dichloromethane / methanol = 9: 1) (3) [[trans-4- [2- (methoxycarbonyl) ethyl] -cyclohexyl] -amino] -methyl acetate Hydrogenated substance melting point: 166-168TC: Hydrogenated in the presence of methanolic hydrochloric acid.

Rf value: 0.69 (silicone; methane / methanol / concentrated ammonia water = 95: 5: 1) Example of window XT Measure R 1-7, 醅

iL 6.2 g of N- [trans-4- [2- (methoxycarbonyl) ethyl] cyclohexyl] -benzylamine-hydrogenated compound, 12.8 g of N-ethyldiisopropylamine and 5.0 g of 2- Bromoethanol was stirred at 100 for 22 hours and then cooled. The mixture was separated between ethyl acetate and water, and the aqueous layer was extracted with ethyl acetate and washed with the saturated ethyl acetate layer and saturated brine. The ethyl acetate layer was evaporated and the residue was chromatographed on a silica gel column using dichloromethane / methanol (9: 1). Yield: 5.1 g (80¾ of theory),

Rf value: 0.67 (silicone; dioxane / methanol = 9: 1) The following compounds were prepared from similar Example XI: (1) H- (3-hydroxypropyl) -N- [trans-4- [2- (Methoxycarbonyl) -ethyl] cyclohexyl] -benzylamine value: 0.70 (silicone; dichloromethane / methanol = 9: 1) (2) N-benzyl-[[trans-4-[(2 -Methoxycarbonyl) -ethyl] cyclohexyl] amino-72- This paper uses Chinese National Standard (CNS) A4 specifications (210_X297 mm) ........... ........................................ ................................... TΓ .... .......... Mian (please read the notes on the back before filling this page) A6 B6 Printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs. V ^ V. Description of the Invention (71)]-Acetic acid Methyl ester value: 0.86 (silicone; cyclohexane / ethyl acetate = 3: 7) (3) 3-ethyl-7-nitro-2,3,4,5-tetrahydro-1H-3-benzo Nitrogen Seven Parks R * Value: 0.32 (silicone; Dichloromethane / methanol = 95: 5) 啻 伦利 XTTH-"Trans-Vitamin 1 Ethyl 1 Cyclohexyl 1-fluorenylamine-hydrogenated SL 8.0 g of methyl 3- (trans-4-aminocyclohexyl) propionate-hydrogenated, 4.3 g of benzaldehyde and 5.0 ml of triethylamine 150 ml formazan 1.0 g Ramey nickel hydrogenated at 50 psi for 4 hours under 50 psi argon pressure. After cooling, the mixture was aspirated and the filtrate was evaporated. The residue was separated between ethyl acetate and water. The aqueous layer was M The sodium hydroxide solution was adjusted to pH 8-9 and KZ «ethyl acetate extraction. The combined ethyl acetate layer was washed, dehydrated and evaporated with K saturated brine. The residue was suspended in ether and mixed with methanolic hydrochloric acid. The precipitate was evacuated It was washed with ether, washed and dried. Yield: 7.4 g (66¾ of theoretical value), melting point: 170-172¾, theoretical value: C 65.47 Η 8.40 Ν 4.49 Cl 11.37 experimental value: 65.38 8.44 4.46 1 1.40 g 剜 XTTT f Trans-4-amine damages R) argon π-hexyl ester-gas vaporized hydrogenated gas into 59.4 g (trans-4-aminocyclohexyl) oxyacetic acid third butyl solution based on 500 ml of methanol for 1 hour , Cooling in an ice bath, and then stirring the mixture at room temperature overnight. It evaporates to dryness, and the residue is mashed with propane (please read the precautions on the back before filling this page) -Packing.. «J. .Silk. -73- The standard of this paper is to apply for National Standards (CNS) A4 (210X297 mm) Central Bureau of Standards HIGHLAND consumer cooperatives A6 B6 five described (72) and the solid was crushed invention Sui and dry suction case too. Yield: 34.3 grams (59 »of theoretical value) · Melt: 157-160”

Window 锎 XTV -Three Argon 7, 龅 -2.H5-Fg — 1H-3- Cage # 一 匍 十 圜 -7---3.4-二 値 -2H..H2.R- 臃 二 睐- 1.1- Di argon wound a) N- (2-gauge) j Fuyi brewed a certain gas 1 H-3-cage # 1 氤 屮 round-7-V- 碴 醏 二 BB tickled 7.6 grams 7 -Amino-3-trifluoroacetamido-2,3,4,5-tetrahydro-1H-3-benzodiazepine and 7.7 ml of H-ethyldiisopropylamine in 70 ml of dioxane In a mixture of methane, 4.8 g of [(2-aminoethyl) amino] sulfonium in 30 ml of dichloromethane was added dropwise at -5 torr. The mixture was stirred for 1 hour at 0 t: and overnight at room temperature. The reaction solution was diluted with dichloromethane and washed with M water, 1 equivalent strength hydrochloric acid and then with M water. The organic layer was purified by dehydration, evaporation, and residue K chromatography on a silica gel column using cyclohexane / ethyl acetate (1: 1). Yield: 7.8 g (72¾ of theory), Melting point: 128-130¾ Value: 0.64 (silicone; cyclohexane / ethyl acetate = 1: 1) b) 2- (3-tris (2,3-tetramethylacetin) -2 .: ^ .4.5- 四 《— 1 ^-笼 # 一 氤 ·! --- 7- 某） -3.4- 二 瘇 -UH-1.2.5- 了 二 皡 -1.1- H M. 7.8 grams of Example XlVa The compound was dissolved in 20 ml of dimethylformamide and mixed with 2.5 g of potassium third butoxide. After stirring at room temperature for 3 hours, it added 74 paper sizes (CNS) A4 specification (210X297 mm) ... ................ i .ii ……: ... !! -:! ...- Order (please read the notes on the back before filling in this page) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A6 _ B6 _ V. Description of the invention (73) Enter 300 liters of 15¾ citric acid aqueous solution And extracted 3 times with ethyl acetate. Youhe Youyi was dehydrated and evaporated, and the residue was purified by chromatography on a silica gel column using cyclohexane / ethyl acetate (1: 1). Yield: _ 2.1 g (30¾ of theory), Melting point: 165-167Ϊ:

Rr value: 0.30 (silicone; cyclohexane / ethyl acetate = 1: 1)

Dang Lili X V (3-Tian Shi-2 ..?. 4. Only-Four Channels and One 1 {^ 3- Cage # 一 值 + * Pu-7-some)-«18

I in 7,1 g of 7-iodo-3-methyl-2,3,4,5-tetrahydro-1H-3-benzo-nitrogen seven groups [Rf value: 0.85 (silicone; toluene / dioxane / Methanol / concentrated aqueous ammonia = 20: 50: 20: 5); prepared from the compound of Example VI by reaction with sodium hydroxide solution / formaldehyde and then with formaldehyde solution / formic acid] in 50 ml of ether, in -70 to -75t: Dissolve 17.7 ml of 1.6 mol n-butyl lithium in hexane. After -7 0 t: stir for 30 minutes • Add 5.7 ml of triisopropyl borate in 30 ml of ether to the reaction solution. Thereafter, the mixed solution was seeded at -75 t: for 1 hour * and then warmed to -50 t :. After adding 70 ml of water and stirring at room temperature for 1 hour, the aqueous layer was separated. The aqueous layer was adjusted to pH 8-8.5 by glacial acetic acid. Sinking is filtered, washed with a small amount of cold water and dried at 60t. Yield: 3.7 g (73¾ of theory), Melting point: 153-155 t: (from 148 1C sintering) Value: 0.80 (reverse phase silicone, methanol / 5¾ brine = 6: 4)

When the oil {Example XVT —7 5 — This paper size uses the Chinese National Standard (CNS) T 4 specifications (210 X 297 mm) — {Please read the precautions on the back before filling the nest page}-binding Printed by A6 _B6_ of the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 5. Description of the invention (74)眯 _-2- 酾 a) M- (2.2,7, 璧: some 7, some) -4- 笮 argon a cage sugar from 4-benzyloxyaniline and bromoacetaldehyde diethyl acetal in N- Prepared in the presence of ethyl diisopropylamine.

Rf value: 0.42 (silicone; cyclohexane / ethyl acetate = 85:15) b) MU- argon in a certain cage) -H- (2.2 -diethyl hydrogen in some ethyl) -N'-Γ2- ( Ar 钺 钺 1- 腩 from N- (2,2-diethoxyethyl) -4-benzyloxyaniline and [2- (ethoxycarbonyl) ethyl] -isocyanate. Value: 0.45 ( Silicone; Cyclohexane / Ethyl acetate = 1: 1) c) 1- (4- 笮 Argon in a cage) -3- 「2- (7, Argin in a certain cage) Beibubu-Secondary Post -_ From N- (4-Benzyloxybenzyl) -N- (2,2-diethoxyethyl) -N '-[2- (ethoxycarbonyl) ethyl] -urea and trifluoro Acetic acid is prepared in dichloromethane. Melting point: 66-68t: 1 value: 0.41 (silicone; cyclohexane / ethyl acetate = 1: 1) d) 1- (4- 筠 a certain cage) -3-7 · , Argon, carbonyl), ethyl, 1 tetraglucamidine _ -2-_ from 1- (4-benzyloxyphenyl) -3- [2- (ethoxycarbonyl) ethyl] -3H-dihydrofluorene Izo-2-amidine is prepared by hydrogenation in ethanol at 40 ° C and 50 psi hydrogen pressure in the presence of Pd / C. 1 value: 0.20 (silicone; dichloromethane / formaldehyde = 100: 2) e) 1 -"2- (Ethyl argonyl), Ethyl 1-3- U- (Three argon, argon, argon, a certain 7 6 _ _ This paper uses national standard (CNS) A.4 specifications ( 210X (297 mm) .............................. ......: ... fitting: ...: ...: ... order ...: ... line (please read the precautions on the back before filling this page) _____B6___ V. Invention Description (75))-Phenyl tetrazolium favor-Since 1- (4-hydroxyphenyl > -3- [2- (ethoxycarbonyl) ethyl] -dihydrooxazol-2-one and Trifluoromethanesulfonic anhydride was prepared in pyridine at 0 t: melting point: δ 83 = value: 0.66 (silicone; dichloromethane / methanol = 100: 1) Theoretical value: C 43.90 Η 4.18 N 6.83 Cl 7.81 Experimental value: 43.92 4.20 6.98 7.91 g of fine fluorene 1 1-(1-aminoxanthoquinone-fi-even) -3- "4- (2-fluorene 21-one) -cage 1-tetrakimidazole- 2- 酽 x 1 7k x 1.2 醏 300 mg 3- [4- (2-carboxyethyl) phenyl] -1- (1-chloroisoquinolin-6-yl) -tetrahydroimidazole-2 -Ketone, 895 mg of diethylamine [amine and 524 g of potassium carbonate are mixed in a mortar, and then heated to 200 t under nitrogen and nitrogen: 3 hours. After cooling, the mixture is combined with 20 ml of water Use 1 equivalent of hydrochloric acid to adjust the pH to 8-9. The sinker was filtered by suction and washed several times with K water. After drying, the pellet was suspended in 50 ml of dichloromethane / formaldehyde (4: 1) and exposed to ultrasound for 30 minutes in an ultrasound bath. The precipitate was subjected to suction filtration and M diazemethane / methanol repeated treatment twice in an ultrasonic bath. The filter paper residue was stirred in a mixture of 30 ml of methanol and 10 ml of glacial acetic acid under slow heating. The insoluble material was filtered off and the mother liquor was evaporated to dryness. The residue was mixed with toluene again and evaporated. It was then dried under vacuum at 60 t. Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs {Please read the notes on the back before filling in this page) Yield: 70 mg (theoretical value of 20 »〇, melting point: > 250T :, value: 0,78 (reverse Phase Silicone; Methanol / 5¾Brine = 8: 4) -77- This paper size is printed in the middle of a difficult country (CNS) A4 size (210x297 mm) Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs. A6 B6 V. Description of the invention (76) Theoretical value: C 60.25 Η 5.79 Ν 12.01 Experimental value: 60.20 5.43 1 1.54 Mass spectrum: fT = 376 g Example 2 3-U- (2-撖 某一 某) ¾ even 1-1 -Π-毎 [里 见 瞅 -fi -some four g 眯 _-2- 蒯 1g 1- (1-azaisoquinolin-6-yl) -3- [4- (2-methoxycarbonyl) -Ethyl] benzyl] -tetrahydroimidazol-2-one, 100 ml of dioxane, 80 ml of water and 8.5 ml of 1 equivalent sodium hydroxide solution was stirred at room temperature for 3 hours. 9 ml of 1 equivalent hydrochloric acid was added The mixture was evaporated and the precipitate was filtered by suction. The product was washed with water and dried at 50C. Yield: 0.78 g (80¾ of theory), melting point: 236-240 1: (decomposition)

Rf value: 0.36 (silicone; dichloromethane / ethanol / ethyl acetate = 20: 1: 1) The compound was prepared from analogous to Example 2: (1) 1- [4- (2-carboxyethyl) benzene [Methyl] -3- (isofluorin-6-yl) -3） -dihydroimidazol-2-one Melting point: 305.310¾, 1 ^ value: 0.49 (silicone; dichloromethane / methanol = 9: 1) Theoretical value : C 70.18 Η 4.77 Ν 11.69 Experimental value: 69.95 4.93 1 1.64 (2) 1- [4- (2-fluorenylethyl) benzyl] -3- (1,2,3,4-tetrahydroisoquinoline -6-based) -tetrahydroimidazol-2-one-78 — This paper uses China National Standard (CNS) A4 specification (210X 297 mm) '{Please read the precautions on the back before filling this page } -Pack-TΓ. Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs _B6__ V. Description of the invention (77) Rr value: 0.44 (reverse phase silicone; formazan / 5¾ saline solution = 6: 4) Theoretical value: C 67.54 Η 6.21 Η 11.25 寊 Test value: 67.58 6.42 11.23 (3) Bu [4- (2-fluorenylethyl) benzyl] -3- (2,3,4,5-tetrahydro-1Η-3-benzyl Triazine-7-yl) -3H-dihydroimidazol-2-one (4) 2- [trans-4- (2-methoxycarbonyl) ethyl] -5- (2,3,4, 5-tetrapyrene-1H-3-benzylazine-7-yl) -3,4-dihydro-2H, 5H-1 , 2,5-thiadiazole-1, 1 -dioxide was performed in a methanol / sodium hydroxide solution; starting material: the compound of Example 18. 1 ^ value: 0.36 (reverse phase silicone; methanol / 5¾ brine = 6: 4) (5) 3- [4- (2-carboxyethyl) phenyl] -1- (2,3,4, 5- Tetrahydro-1H-3-benzomonoazine-7-yl) -tetrahydroimidazole-2,4-dione (6) 1- [4- [2-carboxy-2- (n-butylsulfonylsulfonium Aminoamino) -ethyl] benzyl] -3- (2,3,4,5-tetrahydro-1 [1-3-benzomonoazine-7-yl) -tetrahydroimidazole-2- Ketone (7) 1- [4- [2-Carboxy-2- (n-pentyl-chitylamino) -ethyl] phenyl] -3- (2,3,4,5-tetrahydro-lH-3 -Benzobenzoazine-7-yl) -tetrahydroimidazol-2-one (8) [4- (2-carboxyethyl) phenyl] -3- (5,6,7,8-tetrakis Hydropyrido [3,4-d] pyrimidin-2-yl) -tetrahydroimidazol-2-one (9) 1- [4-[(carboxymethyl) sulfonyl] phenyl] -3- (2 , 3,4,5-tetrahydro-1H-3-benzodiazepine-7-yl) -tetrahydrooxazol-2-one (10) 1- [(4-carboxy-buhexahydropyridyl ) Carbonylmethyl] -3- (2,3,4,5- (Please read the notes on the back before filling in this page) -79 — This paper Λ degree is applicable to the national standard (CNS) 肀 4 specifications (210x297 mm) A6 B6 printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 5. Description of the invention (78) Tetrahydro-1H-3-benzo-nitrogen seven groups-7-yl) -tetrahydroimidazole-2- 酽(1 1) 1- [2-[(2-Carboxyethyl) aminocarbonyl] ethyl] -3- (2,3,4,5-tetrahydro-1H-3-benzo-nitrogen seven countries-7- ) -Tetrahydrooxazol-2-one (12) 1- [4- (2-carboxyethyl) benzyl] -3- (2,3,4,5-tetrahydro-111-2-benzo Hepta-7-yl) -tetrahydroimidazol-2-one (13) 1- [4- (2-carboxyethyl) phenyl] -3- (1,1-dimethyl-1,2 , 3,4-tetrahydro-isoquinoline-6-yl) -tetrahydrooxazole-2-fluorene Example 3 1- (1-retention dark Bft-fi-some)-·? -Γ4-Γ2 -(Methyl argon, a sugar, a certain, a, a cage, a 1-tetra argon, a 2-tetrahydropyrene, 2-gram, 22 grams of 1- (isoquinoline-N-oxide-6-yl) -3- [4- [2- ( Methoxycarbonyl) -ethyl] phenyl] -tetrahydrooxazol-2-one and 25 ml of phosphorus oxychloride were refluxed for 2 hours. Then the oxygenated phosphorus was distilled off and the residue was mixed with ice. PH of the mixed solution Use saturated sodium bicarbonate solution to adjust to 8-9. Its M dichloromethane extraction several times, the organic was dehydrated and evaporated and the residue K-dialysis method was purified in a silica gel column using dichloromethane / methanol (20: 1) . Yield: 1.0 g (43¾ of theory),

Rf value: 0.66 (silicone; methane / methanol = 20: 1) Example 4 of the window 1- (Liu Mu 瞅 -fi- 珥 珥 羝 羝 某 1-cage 1- 1-tetra argon _ 酾 3.0 3.0 G of N- (2-hydroxyethyl) -1Γ- (isoquinolin-6-yl) -H- [4- [2- (methoxycarbonyl) -ethyl] phenyl] -urea and 2.0 g of tris Benthylphosphine is added to 105 ml of acetonitrile, and 1.31 ml of diethyl azodicarboxylate-80 is added at 42 to 52¾- This paper is applicable to the national standard (CNS) A4 specification (210X297 mm y ~~). ........................................ ............ Outfit ……………… Order …………, (Please read the precautions on the back before filling in this page) Annoyance 1 |: · Staff Consumption of Central Standards Bureau, Ministry of Economic Affairs Printed by a cooperative

Scoop in 36 ml of ethoxylate. After stirring at 45 t for 2 hours, the mixture was cooled to -5 C and stirred for another 2 hours. The precipitate was filtered by suction and washed with cold acetonitrile. Yield: 2 · 6 g. (Theoretical value i 3 〇 X;), melting point: 2 1 3-2 1 5 »I 埴: 0. Β〇ί'silicone ; Diazomethane / methanol = 20 ·· 1: 1) The following compounds are similar to the decoration of Example 4: ':] > 1-('. 3- 茕 tributoxycarbonyl-2,3,4, 5-Cyclohydro-1 «-3-benzo-pyridine-7-yl) -3- [4-ί2-ίmethoxyfluorenyl) ethyl] cyl: -tetrahydro_ ran-2- _ ： 1 6 Β-1 6 7 * I ί Speech: 0. 7 7 (Nep; dichloromethane. / Ethyl acetate = 9: i) |, 2 > ί- [反-[4-[2- (Methoxycarbonyl) ethyl] cyclohexyl] -3- (3-trifluoroethyl-yl-2,3,4,5-tetrahydro-1 «-3-capped-nitrogen ±: 圜 -7- Base) -tetrahydrocycline 2 2-嗣 瑢 IA: 250-255tM. Decomposition), h value: 0.45 (silicon hydrazone; cyclohexane / ethyl acetate = 1: 1) (3) Bu [4- [反-2- (trioxycarbonyl) vinyl] phenyl] -3-ί3-trifluoroethyl_lane-2,3,4,5-tetrahydro-11 "!-3-benzo-nitroazine- 7-yl) -tetrahydroalyzol-2-_ 锫 point: 21β-22〇υ, R letter ·· 0.3 δ (silicon; cyclohexane / ethyl acetate = 1 ·. 1) 『4 ) 1- [trans-4- [2- (Cyclooxycarbonyl) ethyl 1cyclohexyl ] -3- (3-trioxethenyl-2.3,4.5-tetrahydro-14-3-cage and one nitrogen heptam-7-yl)-(Please read the precautions on the back before filling this page) i clothing.

， 1T This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) A6 B6 Printed by the Consumers' Cooperatives of the Bureau of Standards of the Ministry of Economic Affairs 5. Description of the invention (80) 3,4,5,6-Tetrahydro- 1 {1-pyrimidine-2-_ Melting point: 125-127¾, Rr value: 0.54 (silicone; cyclohexane / ethyl acetate = 1: 2) g 5 5 1- (Leucine-6-some)- 3-Ur? .- (g arg 镅 镅 某 卜 某 Η 二-2 眯 眯--2-7.3 g of N- (2,2-diethoxyethyl) -N '-(iso Quinoline-6-yl) 4- [4- [2-1methoxycarbonyl) ethyl] phenyl] -urea was seeded in 35 ml of trifluoroacetic acid at room temperature for 2 hours. The mixture was then partially evaporated and ice water was added. Its M sodium hydroxide solution was made alkaline with stirring and cooling. The precipitate was filtered by suction and washed with a little methanol. The product was then recrystallized from methanol. Yield: 4.45 g (76¾ of theory), Melting point: 15 8 -1611 :, Value: 0.29 (silicone; dichloromethane / methanol = 95: 5) Theoretical value: C 70.76 Η 5.13 Ν 11.25 Experimental value: 70.52 5.08 1 The compound at 1.35 was prepared from Example M in Example 5: (1) 1- [trans-4- [2- (methoxycarbonyl) ethyl] cyclohexyl] -3- (3-trifluoro —., · , R ·-., .- 1-I ethylamido-2,3,4,5-tetrahydro-111-3-benzo-nitrogen seven-cycle-7-yl) -3 [1-dihydrooxazole The 2-ketone M was dry-heated to 160-170 1C. Melting point: 121-124¾ 1 value: 0.35 (silicone; cyclohexane / ethyl acetate = 1: 1) (2) 1- [trans-4-[[(methoxycarbonyl) methyl] oxy] -cyclohexyl ] -3- (3- 三 82 This paper uses the national standard of China (CNS). A4 specifications (210X297 mm) {Please read the precautions on the back before filling this page)-Binding. 4: Π 01259_The application of the patent application says that the book is revised, page E ('March 1986 Y Β7 Description of invention (other) Η £ ί 7f Oxytotenyl-2 VtrirS —- " W-Hydrogen'-1H -3 -Benzazine-7-yl) -3H -Dihydromeptyl-2-_ Melting point: 1 4 8-1 4 9 t R f value: 0 · 2 S (pentane gum; ethyl acetate Ester / Cyclohexane = 2: 1) (3) ethoxycarbonyl) -1-propyl] cyl] -3- (3-trifluoroethylazinyl-2, 3, 4, 5 -tetrahydro- 1 fluorene-3 -benzodiazepine-7 -yl) -3 fluorene -dihydroH sedum-2-_ h grass: 0.32 (silicon hydrazone; cyclohexane / ethyl acetate | _ = 2: 1 > t4) 1- [trans-4- [2- (Senoxyfluorenyl) ethyl.] cyclohexyl] -3- (3-ethyl-2. 3, 4. F '-tetrahydro-1 Η- 3 -Canomonoazine-7-yl) -3 hydrazone-dihydro-oxazole 30 (reverse phase silicon P; methanol / 5% saline = 6: 4) trans-4 methoxycarbonyl) ethyl Huanji ] -3- (7-ethyl (please read the precautions on the back before filling this page) Hydrogen 暁 m S5; τρ; Sc? Huang 酴 (6) 氡 B R value (7) -6.7 _, 8 , 9 -tetrahydro-5H-pyridine P # benzo [2,3-d] —nitrosepta-2-yl) -3H-di beer-2-Er: 1 3 5-1 3 6 T: value: C 6 4, ¢, 1 Η 7.78 Ν 16.38 堉: 64. 8 2 7.84 16.27 [4- [2- (ethoxycarbonyl) -buphenyl-ethyl] cyl] -3- (3-trimene Vol.-2,3,4,5-Tetrahydro-1! ^-3-benzo-azepta-7-yl) -34 Slube-2-_: 0. 2 4 (δ々p; ring Hexane / ethyl acetate = 7: 3) [Trans-4- [2- (methoxycarbonyl) ethyl] cyclohexyl] -3- (7-benzyl, 8, 9-tetrahydro-5 Η -Pyrimido [4,5-d] —Aza-Hepta-2 -Base] -3 Η -2-8 3 A paper size is applicable to China National Standard (CNS) A4 specification (210X297 mm) 5. Description of the invention ( 82) Printed Hydroimidazol-2-one by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs Melting point: 131-134¾ Value · 0.38 (silicone; Dichloromethane / methanol = 20: 1) g Lun ft (1) 1-U -"2- (formamyl, oxazine, B, 1,2, tetramethyl-S-quinoline-fi-tetramethyl-methyl-88-ester) 2.0 g 1- (isopyridin-6-yl) -3- [4- [2- (methoxy Carbonyl) ethyl] - Ben-yl] -3H- dihydro-imidazol-2-one in 50 liters of glacial acetic acid M0.5 Um g platinum oxide was hydrogenated at 50 PSI hydrogen pressure and room temperature for 40 minutes. The catalyst was filtered, the filtrate was evaporated and the residue was recrystallized from formazan. Yield ': ί. 7 g (72 * of theory), melting point: 170-173 ° C (decomposition) Theoretical value: C 65.59 Η 6.65 Η 9.56 Experimental value: 65.90 6.78 9.69 L value: 0.30 (silicone; toluene / di Oxygen / methanol / concentrated ammonia = 20: 50: 20: 5) Mass spectrum: M + = 379 (2) 1- [trans-4- (2-fluorenylethyl) cyclohexyl] -3- (3 -Methyl-2,3,4,5,53,6,7,8,9,93-decahydro-111-3-benzodiazepine-7-yl) -tetrahydroimidazole-2 -Ketone X 1.35 HC1 X 1.9 H2 0 using dioxane / water and platinum-rhodium catalyst. The compound of Example 19 was used as a starting material. Mass spectrum: M * = 405 Theoretical value: C 56.49 Η 9,10 Ν 8.5 Cl 9.79-8 4-a little θ V This paper size is in accordance with China National Standard (CNS) A4 (210X297 mm) (please first Read the notes on the back and fill in this page) __ B6__ V. Description of the invention (83) Experimental value: 56.63 8.81 8.60 9.92 (3) 1- [trans-4- (2-carboxyethyl) cyclohexyl] -3- ( 2,3,4,5,5a, 6,7,8,9,93-decahydro-111-3-benzotriazine-7-yl) -tetrahydroimidazol-2-one X 1.05 HC1 X 0.9 Hz. Dioxane / water and platinum-rhodium catalyst were used. The compound of Example 14 (1) was used as a starting material. Mass spectrum · · M * = 391 Theoretical value: C 59.43 Η 9.03 Η 9.45 Cl 8.05 Experimental value: 59.49 8.83 9.35 8.30 The following compounds were prepared from similar to Example 6: (1) 1- [Trans-4- [2-( Methoxycarbonyl) ethyl] cyclohexyl] -3-(1,2,3,4-tetrahydro-isoquinolin-6-yl) -tetrahydrooxazol-2-one-acetate (2) 1 -[Trans-4- (2-carboxyethyl) cyclohexyl] -3- (3-methyl-2,3,4,5,53,6,7,8,9,93-decahydro-1! 1-3-Benzodiazepine-7-yl) -tetrahydroimidazole-2-fluorene-hydrochloride The compound of Example 19 was used as a starting material.啻 抡 剜 7 1-U- 「2- (Both strontium, strontium, strontium) 7, some 1 茏, 1-1-3- (1 U.4-tetrapoor decaquine-6-yl) -Siqi -2- 酽 -M gaseous substance X 1 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Water Economy {Please read the precautions on the back before filling out this page} Stirring hydrogen with 150 mg [4- (2- Carboxyethyl) benzyl] _ 3- (1,2,3,4-tetrahydro-isoquinolin-6-yl) -tetrahydroimidazole-2-fluorene in a suspension of 4.6 ml of isobutanol for 30 minutes The mixture was stirred at room temperature overnight. Propylene was added and the mixture was evacuated. The product was suspended in acetone, filtered by suction, washed with acetone and ether and dried. —85 — This paper / Ut · Furniture CCNS) 4 specifications (210x297 life love A6 B6 Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs. 5. Description of the invention (84) Output: 140 ： g (77¾ of theoretical value), Theoretical value: C 65.56 Η 7.04 Η 9.18 Cl 7.74 Experimental value: 65.38 7.03 9.47 7.92 Rr value: 0.19 (reverse phase silicone; methanol / 5¾ saline solution = 6: 4) Mass spectrum: M * = 421 M The compound was prepared similarly to Example 7: (1) 1- [4- [2- (isopropoxycarbonyl) ethyl] phenyl] -3- (2, 3,4,5-tetrahydro-1Η-3-benzodiazepam-7-yl) -tetrahydromeptan-2-one-hydrogenated theory Theoretical value: C 63.0 8 Η 7.20 Κ 8.83 Cl 7.45 Experiment Value: 6 2.79 7.14 8.83 7.80 Rr value: 〇21 (reverse phase silica gel; methanol / 5JK saline solution = 6: 4) Mass spectrum: M + = 421 (2) 1- [4- [2- (cyclohexyloxy) Carbonyl) ethyl] phenyl] -3- (2,3,4,5-tetrahydro-1fluorene-3-benzodiazepine-7-yl) -tetrahydroimidazol-2-one-argon Compound (3) 1-U- [2- (methoxycarbonyl) ethyl] phenyl] -3- (3-methyl-2,3, 4.5-tetrahydro-111-3-benzotriazine (Central-7-yl) -tetrahydroimidazol-2-one-hydrogenated compound X 0.75 Η20 Melting point: 248-250¾, Theoretical value: C 63.01 Η 6.94 Η 9.19 Cl 7.75 Experimental value: 63.09 6.98 9.22 7.88 Value: 0 · 25 (Reverse phase silicone; methanol / 5ί! Saline solution = 6: 4) (4) 1- [4- [2- (ethoxycarbonyl> ethyl] phenyl] -3-(3-methyl-2, 3, 4.5- tetrahydro-111-3-benzo-nitrogen seven-ring-7-yl) -tetrahydro-2-methyl-2-hydrazine-hydrochloride-86- This paper is based on the national standard of China. (CNS ) A 4 size (210X297mm) installed ... ..... line (. Please also read the notes on the back again (This page)) Printed by the Central Standard Tail Employee Consumer Cooperative of the Ministry of Economic Affairs + A6 ____B6_ V. Description of the invention (85) " Value: 0.22 (reverse phase silicone; methanol / 5¾ saline = 6: 4) (5) 1- [ 4- [2- (isopropoxycarbonyl) ethyl] benzyl] -3- (3-methyl-2, 3,4,5-tetrahydro-111-3-benzo-nitroazine-7 -Based) -tetrahydroimidazol-2-one-hydrogenation value; 0.19 (reverse phase silicone; methanol / 5 «brine = 6: 4) (6) 1- [trans-4- [2- (isopropyl Oxycarbonyl) ethyl] -cyclohexyl] -3- (3-methyl-2,3,4,5-tetrahydro-111-3-benzotriazine-7-yl) -tetrahydroimidazole The -2-keto-hydrogen atmosphere uses sulfite atmosphere and hydrogen chloride. Melting point: > 250Ό, Value: 0.17 (reverse-phase silicone; methanol / 5: «brine solution = 6: 4) Theoretical value: C 65.32 Η 8.43 Ν 8.79 Cl 7.42 Experimental value: 65.10 8.41 8.91 7.66 (7) 1- [ Trans-4- [2- (ethoxycarbonyl) ethyl] cyclohexyl] -3- (3-methyl-2,3,4,5-tetrahydro-111-3-benzodiazepine- 7-yl) -tetrahydroimidazol-2-one-hydrogenated sulphur chloride and hydrogen chloride. Melting point: > 250Ό, value · 0.24 (reverse-phase silica gel; methanol / 5¾ brine = 6: 4) theoretical value: C 64.71 Η 8.25 Ν 9.09 Cl 7.64 experimental value: 64.09 8.22 9.08 7.72 (8) 1- [Reverse -4- [2- (methoxycarbonyl) ethyl] cyclohexyl] -3- (3-methyl-2,3,4,5-tetrahydro-111-3-benzomonoazine seven group-7 -Yl) -tetrahydroimidazol-2-one-hydrogen odorant ............ ..................................... ....... ΤΓ ..........._ (Please read the notes on the back before filling This page} — 8 7 — The paper size is free to use country t. National Standard (CNS) A4 specification (210X297 mm) Printed by A6 B6 of the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (86) Use of subtraction鹾 Fluorine and hydrogen chloride. Melting point: > 250X :, 1 value: 0.29 (reverse phase silica gel; methanol / 5¾ saline solution = 6: 4) Theoretical value: C 64.05 Η 8.04 Ν 9.34 Cl 7.88 Experimental value: 64.10 7.97 9.52 8.11 (9) 1- [trans-4- [2- (isopropoxycarbonyl) ethyl] -cyclohexyl] -3- (2,3,4,5-tetrahydro-111-3-benzyl Nitrogen-7-yl) -tetrahydropanazol-2-one-hydrogenated Sulfur atmosphere and hydrogenated hydrogen. Value: 0.20 (reverse phase silicone; methanol / 5¾ brine = 6: 4) (10) 1- [trans-4- [2- (ethoxycarbonyl) ethyl] cyclohexyl ] -3- (2,3,4,5-tetrahydro-1H-3-benzotriazine-7-yl) -tetrahydroimidazol-2-one-hydrogenation using thionyl chloride 1 ^ value: 0.23 (reverse phase silica gel; methanol / 5¾ brine = 6: 4) theoretical value: C 64.05 Η 8.06 Ν 9.34 Cl 7.88 experimental value: 63.77 8.23 9.07 7.91 (11) 1- [Trans-4 -[2- (methoxycarbonyl) ethyl] cyclohexyl] -3-(2,3,4,5-tetrahydro-1H-3-benzotriazine-7-yl) -tetrahydroimidazole -2-Ketone-hydrochloride 'uses thionyl chloride and hydrogen chloride. Value: 0.26 (reverse phase silicone; methanol / 5¾ brine = 6: 4) Theoretical value: C 63.36 Η 7.86 Ν 9.64 Cl 8.13 Experimental value: 63.34 7.88 9.73 8.1 1 -88 — Chinese paper standard (CNS) A4 specification (210X297 mm) used in this paper size (Please read the precautions on the back before filling this page)-Staff of Central Bureau of Standards, Ministry of Economic Affairs Printed by Consumer Cooperative A6 B6 V. Description of Invention (87) 9 mmr 1- "4-1 ~ 2- (掰 some 7, some) Cage 1-3-(? .- 申 某 -1.2.3.4- 四Bali瞅 -fi- 某) -tetrasilver 脒 _-2- 豳 y fl.? · Ice 350 mg '1- [4- [2- (methoxycarbonyl) ethyl] phenyl] -3- (1, 2,3,4-tetrahydroisopyrine-6-yl) -tetrahydroimidazol-2-one-acetate, 0.7 ml of water, 0.15 ml of formic acid and 0.7 ml of 37% aqueous formaldehyde solution at 65t: stir for 1 hour . Toluene was added and the mixture was evaporated. It was mixed with toluene and evaporated again. The residue was stirred at room temperature for 2 1/2 days with 2 ml of tetrahydrofuran, 1 ml of water and 0.8 ml of a 4 equivalent strength sodium hydroxide solution. Add 220 μg of aerated ammonium in 1 ml of water and stir the mixture for 2 hours. The reaction solution was partially evaporated, cooled with ice and the solid product was filtered by suction. The solid M was washed with water, acetone and ether and then dried. Yield: 220 ml (72¾ of theoretical value), Melting point: 245-248 ¾ Theoretical value: C 68.98 Η 6.68 Ν 10.97 Experimental value: 68.91 6.69 10.92

Rr value: 0.41 (reverse phase silica gel; methanol / 5¾ saline solution = 6: 4) Mass spectrum: M * = 379 The following compounds were prepared from analogous to Example 8: (1) 1- [4- (2-carboxyethyl) ) Phenyl] -3- (3-formamidine-2,3,4,5-tetrahydro-1H-3-benzodiazepine-7-yl) -tetrahydroimidazol-2-one-hydrochloride The final ester cleavage of Compound X 1.5 water was performed with glacial acetic acid / hydrochloric acid instead of sodium hydroxide solution. — 89 — This paper is widely used in the country. National Standards (CNS) A 4 Regulations (I210X297 mm) .. ................................................. ............ installation ............ may ...... ♦ (Please read the precautions on the back before filling in this page) B6 V. Description of the invention (· 88) Theoretical value C 60.45 Η 6.84 Ν 9.20 Cl 7.76 Experimental value: 60.45 6.86 9.18 8.09 I value: 0.31 (silicone; Dichloromethane / formaldehyde / concentrated ammonia = 4: 1: 0.2) Mass spectrum: M * = 39 3

Xuanshi 锎 Q U4-(2-Jinhua Ethyl) phenyl 1-3- (2. 夂 4.5-tetra- 瘇 -11 ^ -cage # 一 氛 · 土 两 -7- 基 四 铕 beer _-; >-黼 800 mg 1- [4- [2- (methoxycarbonyl) ethyl] phenyl] _3_ (2,3, 4,5-tetrahydro-1b 3-benzo-nitroazine 7-7 -Yl) -tetrahydroimidazol-2-one-hydrogenated scented with 10 ml of semi-concentrated hydrochloric acid and 10 ml of glacial acetic acid. After 2 hours' add another 5 ml of semi-concentrated hydrochloric acid and 5 ml of glacial acetic acid and mix the Stir overnight at room temperature. After evaporation of the reaction solution, the residue was suspended in 10 ml of water. "The value K2 equivalent concentration of sodium hydroxide reached 6, the solid was filtered by suction, washed with ice water, and then dried. Yield: 560 mg (theoretical value) 79! «), Value: 0.40 (reversed-phase silica gel; methanol / 5¾ saline solution = 6: 4) Mass spectrum: M * = 379 M The compound was prepared similarly to Example 9: The Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Printed {Please read the notes on the back before filling in this page) (1) 1- [4- (2-carboxyethyl) phenyl] -3- (4aRS, 6l? S, 8aRS) -1,2, 3,4,43,5,6,7,8,8 3-Decylhydroisoline-6-yl) -tetrahydroimidazol-2-one-hydrochloride M Hydrogenated ions: 0.41 ( Reverse-phase silicone; methanol / 5¾ saline solution = 6: 4) —9 0 A paper size is selected from National Standards (CNS) A4 specifications (210X297 mm) Printed by A6, Consumer Cooperatives, Central Standards Bureau, Ministry of Economic Affairs B6 V. Description of the invention (89) Mass spectrum 臞 ·· M + = 371 (2) l- [4- (2-carboxyethyl) phenyl] -3- (3-ethyl-2,3,4,5 -Tetrahydro-1H-3-benzo-nitrogen heptad-7-yl) -tetrahydroimidazole-2-hydrazone-hydrogenated compound value: 0.36 (reverse phase silicone; formazan / 5¾ saline solution = 6: 4) Mass spectrum: ίΤ = 407 (3) 1- [4- (2-carboxyethyl) phenyl] -3- (3-isopropyl-2,3,4,5-tetrahydro-1H-3-benzene Heptazine-7-yl) -tetrahydrooxazole-2-hexyl-hydrogenated compound (4) 1- (2-carboxyethyl) -3- [4- (isoterolin-6-yl) Phenyl] -tetrahydrofluoran-2-one-hydrochloride (5) [[4- (2-carboxyethyl) phenyl] -3- (4,4-dimethyl-1,2,3 , 4-Tetraargon isoquinolin-6-yl) -tetrahydroimidazol-2-one-hydrogenated compound (6) 1- [4- (2_ carboxyethyl) phenyl] -3- (3-butyl -2,3,4,5-tetrahydro-1H-3-benzo-nitrozine-7-yl) -tetrahydrooxazole-2-_ -hydrochloride value: 0.33 (reverse phase silicone; methanol / 5¾saline solution = 6: 4) Mass spectrum: = 4 3 5 (7) 1- [4 -(2-carboxyethyl) phenyl] -3- (triamino-3,4-dihydro-isoquinolin-6-yl) -tetrahydroimidazol-2-one-hydrochloride (8) [4- (2-carboxyethyl) phenyl] -3- (2-methyl-3,4-dihydroquinazolin-7-yl) -tetrahydroimidazol-2-one-hydrogenated compound (9 ) 1- [4- (2-carboxyethyl) phenyl] -3- (4,4-dimethyl-3,4-dihydroUchazolin-7-yl) -tetrahydroimidazole-2- Ketone-hydrochloride (10) 3- [trans-4- (2-carboxyethyl) cyclohexyl] -1- (2,3,4,5-tetrahydro-1H-3-benzyl-nitrogen seven cycles -7-Base] -Allantoin-Hydrochloride Melting point:> 250Ό 91 This paper is used for soil size _ country national standard (CNS) A4 specification (210X297 mm) ... pack ... ............... Order ............ Silk (Please read the notes on the back before filling in this page } Wubi 33101250¾ Patent Examination

The first page of the book says Mengshu Y (Year March 8 β Β7, the description of the invention (? G) year η η supplement a = t methanol / water 詨 =: σττΒ ~ · ΤΊ ^ ~ I; 6: 4) Value: C 6 0 .6 1 H f ..94 H 9,64 Cl 8.13 Value: 6 0 .45 C .90 9. I31. 8.28 Π1) 1- [trans-4- (2-carboxyethyl) cyclohexyl]- 3- (7-ethyl-6,7,8,9-tetrahydro-5 hydrazone-pyridine [2, 3-d] -aminoheptazone-2-yl) -tetrahydrooxazole-2-lane X 2 HC i X 0.y Ha 〇 ^ ΙΑ: 283-286T: t-; pages: (). 4 6 (reverse phase sand; methanol / 5 sodium chloride solution = β: 4) 珲 谙 堉: C 52.36 Η 7.35 Ν 13.88 C 1 14.05 Tribute value: 52.70 7.44 1 3.8 6 14.01 (Please read the notes on the back before filling out this page) Staff Consumer Cooperatives, Central Standards Bureau, Ministry of Economic Affairs > Printed (12) 1-[Anti- 4 -ί 2 -carboxyethyl) cyclohexyl] -3- (3 -ethyl- 2, 3,4, -tetra'f s.- 1 Η-3 -S and one nitrogen_L- 圜 -7- Base)-3H-: bis f oxazole-2 halide m χ 0. 5 Η a 0 R t-value • 0.38 reverse phase silicone.; Methanol / 5¾ _ water = 6: 4) Theoretical value: C 63 .08 Η \ \ 1 Η 9 • 19 G i 7.76 Experimental value: 6 3 .2 6 7 .69 9 .28 7.64 Π 3) 1-[trans-4-(2 -carboxyethyl) cyclohexyl] -3- (2,3,4,5 -tetrahydro-1 Η-3- caged ammonia Heptafluorene- 7-yl] -allantoin-hydrochloride R r if 0.16 (p; dimethylmethane / methanol / concentrated ammonia = 8 0:20 ： 2) 珲 value: C ao .61 Η 6.94 Ν 9 .64 C i 8.13 6 0 .34 6.94 9 .58 8.27! 1 ί) 1-L trans-4-(2-carboxyethyl) cyclohexyl 1-3- (.2,3,4,5-tetrahydro -1H- 3-pyridine-nitrogen-seven-circle-γ __ group) -3,4,5,6-tetrahydro-1H-tumidine-2- -9 2 This paper is applicable to Chinese National Standard (CNS) Α4 Specifications (210X297 mm) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A6 B6__ V. Description of the invention (91) X 1.65 HC1 X 0.7 H2 0 Melting point: 230-235Ϊ: Value: 0.40 (reverse phase silicone; methanol / 5¾ brine Liquid = 6: 4)

(15) 1- (2-carboxyethyl) -3- [4- (3-methyl-2, 3,4,5-tetrahydro-1H-3 -benzo-nitroazine-7-yl) Phenyl] -tetrahydroimidazol-2-one-hydrochloride Melting point: > 2501C

Rr value: 0.20 (reverse phase silicone; methanol / 5 »; saline solution = 6: 4) (16) 1- [trans-4- (2-carboxyethyl) cyclohexyl] -3- (6,7,8 , 9-tetrahydro-5H-pyrimido [4,5-d] -azahepta-2-yl) -tetrahydrooxazol-2-one-hydrochloride

Rr value: 0.53 (reverse phase silicone; methanol / 5¾ brine = 6: 4) (17) 1- [trans-4- (2-carboxyethyl) cyclohexyl] -3- (6,7,8,9 -Tetrahydro-5H-pyropyrano [2,3-d] -azahepta-2-yl) -tetrahydrooxazole-2-copper-hydrogenated compound (18) 1- [trans-4- (2 -Carboxymethyl) cyclohexyl] -3- (6,7,8,9-tetrahydro-5H-pyrido [2,3-d] -azahepta-2-yl) -tetrahydrooxazole-2 -Keto-hydrochloride (19) 1- [trans-4- (2-carboxyethyl) cyclohexyl] -3- (1,2,3,4-tetrahydro-isoquinolin-6-yl)- Tetrahydroimidazol-2-one-hydrochloride (20) 1- [trans-4- (2-carboxyethyl) cyclohexyl] -3- (2,3-dimethyl-3,4-dihydroquine Oxazoline-7-yl) -tetrahydroimidazol-2-one-hydrochloride (21) 1- [trans- 4- (2-carboxyethyl) cyclohexyl] -3- (3-ethyl-2, 3,4,5 -tetrahydro-1H-3-benzodiazepine-7-yl) -tetrahydroimidazol-2-one-hydrochloride 《一 93- This paper uses Chinese national standard (CNS ) Formazan (210x297mm) Pack—… :: Order… i …… Weft (please read the precautions on the back before filling in this page) V. Description of the invention (92) Melting point:> 270¾

Rr value: 0.35 (reverse phase silicone; formazan / 5 »: saline solution = 6: 4) (22) 1- [trans-4- (2-carboxyethyl) cyclohexyl] -3- (3-propyl -2,3,4,5 -tetrahydro-1H-3-benzomonoazine-7-yltetrahydroimidazole-2-fluorene X 1.07 HC1 X 1 H20 melting point; > 250¾ value: 0.32 (reverse phase Silicone; Methanol / 5% saline solution = 6: 4) Theoretical value: C 61.96 Η 8.33 Ν 8.67 Cl 7.83 Experimental value: 62.10 8.14 8.77 7.94 (23) 1- [trans- 4- (2-carboxyethyl) cyclohexyl ] -3- (3-propionyl_2,3,4,5 -tetrahydro-1H-3-benzodiazepto-7-yl) _tetrahydroamido_2_one x 1.1 HC1 X 1.5 H2〇 melting point: > 250 it

Rf value: 0.30 (reverse phase silicone; methanol / 5¾ brine = 6: 4) Theoretical value: C 60.94 Η 8.00 H 8.53 Cl 7.91 Experimental value: 61.32 7.63 8.47 7.82 (24) 1- [Trans-4- (2- Fluorenylethyl) cyclohexyl] -3- (3-isobutyl-2,3,4,5-tetrahydro-1H-3-benzotriazine-7-yl) -tetrahydroimidazole-2 -Ketone-Hydrogenated Aromatics Central Standard of Ministry of Economic Affairs, printed by employee consumer cooperatives (please read the precautions on the back before filling this page)

(2 5) 1- [trans-4- (2-carboxyethyl) cyclohexyl] -3- [3 (2-hydroxyethyl) -2,3,4,5-tetrahydro-111-3-benzene Benzene-7-yl) -tetrahydroimidazol-2-one-hydrochloride Melting point: 2 5 7-2 6 0 1C Value: 0.46 (reverse phase silicone; methanol / 5¾ brine = 6: 4) 94 This paper size is in Chinese National Standard (CNS) A4 size (210x297 mm) Printed by A6 B6, Shellfish Consumer Cooperative, Central Bureau of Standards, Ministry of Economic Affairs 5. Description of the invention (93) (26) 1- [anti -4- (2-carboxyethyl) cyclohexyl] -3- [3- (carboxymethyl)-2.3.4.5- tetrahydro-111-3-benzo-nitroazine-7-yl) -tetrahydro Imidazol-2-one-hydrogenated substance Melting point: > 28010 Value: 0.39 (reverse phase silicone; methanol / 5¾ saline = 6: 4) (27) 1- [trans-4- (2-carboxyethyl) ring Hexyl] -3- [3-benzyl-2,3,4,5-tetrahydro-1H-3-benzo-azaazine-7-yl) -tetrahydroimidazol-2-one-hydrogen flammable compound : ≫ 2 5 0 t:

Rr value: 0.21 (reverse phase silicone; methanol / 5¾ brine = 6: 4) (28) 1- [trans-4- (2-carboxyethyl) cyclohexyl] -3- [3- (cyclopropylmethyl) Radical) -2,3,4,5-tetrahydro-1H-3-benzo-nitrogen heptad-7-yl] -tetrahydroimidazol-2-one • Hydrogenated compound Melting point: > 2 8 0 t: Value: 0.31 (reverse phase silicone; methanol / 5¾ saline = 6: 4) (29) 1- [trans-4- (2-carboxyethyl) cyclohexyl] -3- [3- (cyclopropyl-2 , 3, 4.5-tetrahydro-1 ^ 1-3-benzodiazepine-7-yl) -tetrahydroimidazole-2 -_- hydrochloride (30) 1- [trans-4- (2- Carboxyethyl) cyclohexyl] -3- [3- (cyclohexylmethyl) -2,3,4,5-tetrahydro-1H-3-benzo-azaazine-7-yl] -tetrahydroimidazole -2-keto-hydrochloride (31) 1- [trans-4- (2-carboxyethyl) cyclohexyl] -3- (3-cyclohexyl-2, 3, 4.5- tetrahydro-111-3- Benzoazine group-7-yl) -tetrahydroimidazol-2-fluorene-hydrogenated compound — 9 5 — This paper element is used in the national standard (CNS) A4 (210χ2 ^^ ϋ ^ ....................... ΤΓ ................... (Please read the note on the back first Please fill in this page for further information) Printed by A6 B6, Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of Invention (94) 窨 抡 Μ 10 Ι ^ Γ4- 2- (methylamino glycosyl) ethyl 1 fluorenyl l-3- ^ 2.3.4.S-TO 智-||| -3-¾ and one nitrogen heptamidine-7-some)-four favor -2-Cheat-Mhh compound 2.3 g 1- (3-Third-butoxycarbonyl-2,3,4,5-tetrahydro-1H-3-benzodiazepine-7-yl) -3- [4- [2- (Methoxyl) -ethyl] phenylb-tetrahydroimidazol-2-one was stirred in 30 ml of methanolic hydrochloric acid at room temperature for 2 hours. After the reaction was evaporated, the residue and Stir in ice water, filter with suction, wash with a small amount of formic acid and tert-butyl methyl ether, and then dry. Yield: 1.8 g (90 ° of theory), Theoretical value: C 64.25 Η 6.56 Η 9.77 Cl 8.25 Experimental value: 64.08 6.60 9.92 8.51 Rf value: 0.26 (reverse phase silica gel; methanol / 5¾ saline solution = 6: 4) Mass spectrum_: M + = 393 Example of window 1 1 1-"(4aRS.6RS.8aRS) -1.2.3.4.4 a.fi.fi.7.8.Sa- + Ruili Mugeng-6 -ji) -3-U- "2- (Shen arg, carbonyl, carb, cymbal, cymbal, cymbal, cymbal, cymbal)-Four-value favored duo -2 -Plutonium-argon Servants in 216 mg 1- [4- [2- (methoxycarbonyl) ethyl] phenyl] -3- [(43 feet 5,6 feet 5,831 ^)-2-methyl-1,2, 3,4,43,5,6,7,8,83-decahydroisoquinolin-6-yl] -tetrahydrooxazole-2-fluorene and 185 mg 1,8-bis- (dimethylamine ) -Naphthalene 5 ml of 1,2-dichloroethane, was added 0.09 ml 1-chloro-ethyl carboxylate atmosphere, the mixture stirred at room temperature for 20 broadcast minutes, then refluxed for 2.5 hours. After the reaction solution was evaporated, the residue was combined with 10 ml of methanol and refluxed for 3 hours. The reaction solution was acidified with methanolic hydrochloric acid, evaporated, and chromatographed on a silica gel column (please read the precautions on the back before filling in this page) -pack · -order. -96-This paper is used in countries with difficulty Standard (CNS) 肀 4 (210X297 mm) Printed by A6 B6, Consumer Cooperative of the Central Bureau of Standards, Ministry of Economic Affairs. 5. Description of the invention (95) Purified using digas methane / formaldehyde (92: 8). Yield: 200 g (theoretical value of 873!), Value: 0.35 (reversed-phase silicone; methanol / 5¾ saline solution = 6: 4) rich example 1 2 1- "4-Γ2- (methyl argon carbonyl) B, 1 cage, 1-3-"(/ taRS.fiRS.8aRS) -2-A, -1.2.3.4.43.5.6.7.8.83-+« Li 陲 瞅-(^-某 1-1-4g 眯 _ -?-翮 950 mg 1- [4- [2- (methoxycarbonyl) ethyl] phenyl] -3- [(4aRS, 61 ^, 831 ^)-2-methyl-1,2,3 , 4,43,5,6,7,8,83-decahydroisoquinolin-6-yl] -3H-dihydroimidazol-2-one in 50 ml of ethyl acetate in the presence of Pd / C , Hydrogenated at 50 psi hydrogen pressure and room temperature for 5 hours, and then at 50 hours for 5 hours. The catalyst was decanted and the filtrate was evaporated. The residue was briefly heated with tert-butyl methyl ether, and then stirred to cool. The solid was evacuated Over 滹, K tertiary butyl methyl ether and dry can. Yield: 300 mg (3U of theory), melting point: 1 55-1 57 1

Rr value: 0.29 (reverse phase silica gel, methanol / 5¾ brine = 6: 4) The compound was prepared from analogous to Example 12 at (1) 1- [trans-4- [2- (methoxycarbonyl) Ethyl] cyclohexyl] -3- (3-trifluoroethylfluorenyl-2,3,4,5-tetrahydro-1H-3-benzotriazine-7-yl) -tetrahydrooxazole- 2-ketone melting point: 165-168Ό 1 ^ value: 0.44 (silicone; cyclohexane / ethyl acetate = 1: 1) (2) 1-trans-4-[[(methoxycarbonyl) methyl] oxy] Cyclohexyl] -3- (3-trifluoro-97 — This paper uses the national standard (CNS) A4 specification (210X297 mm) of this country ............... ........................................ ................ TΓ ............ Cable (Please read the back first Note for re-filling this page) A6 B6 printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economy (Central-7-yl) -tetrahydropanazole-2-fluorene Melting point: 146-147¾ Value: 0.26 (silicone; ethyl acetate / cyclohexane = 3: 1) Ethoxycarbonyl) -1-propyl] phenyl] -3- (3-trifluoroethylfluorenyl-2,3,4,5-tetrahydro-111-3-benzotriazine-7- Radical) -3} 1-tetrahydroimid Azole-2-_ value: 0.32 (silicone; cyclohexane / ethyl acetate = 2: 1) (4) 1- [2- [4- (methoxycarbonyl) benzyl] ethyl] -3- ( 3-trifluoroethylfluorenyl-2,3,4,5-tetrahydro-111-3-benzodiazepine-7-yl) -tetrahydroimidazole-2-fluorene Melting point: 143-144t: Value: 0.46 (silicone; cyclohexane / ethyl acetate = 1: 1) (5) 1- [trans-4- [2- (methoxycarbonyl) ethyl] cyclohexyl] -3- (3-ethyl- 2,3,4,5-tetrahydro-111-3-benzodiazepth-7-yl) -tetrahydroimidazol-2-one-hydrogenated compound Melting point: From 230 t: (decomposition)

Rf value: 0.22 (reverse phase silica gel; methanol / 5¾ brine = 6: 4) (6) 1- [trans-4- [2- (methoxycarbonyl) ethyl] cyclohexyl] -3- ( 7-ethyl-6,7,8,9-tetrahydro-5H-pyracino [2, 3-d] -azahepta-2-yl) -tetrahydro.Ivorazol-2-one Melting point: 136 -1381 Value: 0.33 (silicone; dichloromethane / methanol = 9: 1) (7) 1- [4- [2- (ethoxycarbonyl) -1-phenyl-ethyl] phenyl] -3- (3- 三 -98- This paper size uses Chinese country = »quasi (CNS) A 4¾ grid (_210 X 297 mm) ... ........................................ .............. installed ............ may ... ........... (Please read the notes on the back before filling this page) Central Standards Bureau of the Ministry of Economic Affairs®: Printed by the Industrial and Consumer Cooperatives A6 B6 V. Description of the invention (97) Fluorethenyl -2,3,4,5-tetrahydro-1H-benzodiazepine-7-yl) -tetrahydroimidazol-2-one value: 0.22 (silicide; cyclohexane / ethyl acetate = 7: 3) Exact example 1 3 1-"/ 1-" 2- (Shenyiyiyi) ethyl 1 Benzene U-rUaRS.fiRS.hRS) Getian -1 甚 3.4.43.5.6.7.8.83- + 篕Liyan 瞅 -6- 甚 1-; ^ -two Μ oxazole-2-_ at 6.9 g (43 115, 61 ^, 831 ^ ) -6-[(2,2-dimethoxyethyl) -amino] -2-methyl-1,2,3, 4,4a, 5,6,7,8, 8a-decahydroiso In 30 ml of dioxane, 6.4 g of 4- [2- (methoxycarbonyl) ethyl] -phenyl isocyanate was added and the mixture was stirred at room temperature for 2 hours. The reaction solution was evaporated and K 100 ml The formic acid was dissolved, mixed with methanolic hydrochloric acid and refluxed for 20 minutes. The reaction solution was evaporated and the residue was stirred with 200 ml of water. The precipitate K was removed by suction filtration and the filtrate was extracted with ethyl acetate. The organic layer was discarded. The aqueous layer was potassium carbonate The solution was made alkaline and extracted several times with ethyl acetate. The combined ethyl acetate extract K was washed once with saturated brine, dehydrated and evaporated. The crude product K chromatography was used in an alumina column (basic). Ethyl acetate was purified, followed by mashing with K tertiary butyl methyl ether. Yield: 1.03 g (9¾ of theory), 1 ^ value: 0.55 (silicone; toluene / dioxane / methanol / concentrated ammonia = 20:50: 20: 5) The following compounds were prepared from similar to Example 13: (1) [4- [2- (methoxycarbonyl) ethyl] benzyl] -3-[(4aRS, 6RS, 8aRS) -2-methyl-1,2,3,4,4a, 5,6,7,8,8a-decahydroisodarolin-6-yl-99-paper Du Lin uses China National Standard (CNS) A4 specifications (210 X 297 mm) (Please read the precautions on the back before filling in this page). Binding. Binding. Staff of the Central Standards Bureau of the Ministry of Economic Affairs # Cooperative Society Printing A6 B6 V. Description of the invention (98)]-3H-dihydroimidazole-2- 嗣 X 0.3 Water melting point: 140-145T: Theoretical value: C 68.56 Η 7.91 Η 10.43 Experimental value: 68.49 7.97 10.51 (2) 1- [2 -[4- (methoxycarbonyl) phenyl] Zyl] -3- (3-trifluoroethylfluorenyl-2,3,4,5-tetrahydro-111-3-benzomonoazine- 7-yl) -311-dihydrooxazole-2-m amine and isocyanate were stirred in dioxane at room temperature and then in a steam bath. Omit the treatment with formic acid. The [2- [4- (methoxycarbonyl) phenyl] ethyl] -isocyanate K used was prepared by reacting the corresponding amine-hydroxide with dicarbonylated carbonyl.

Melting point: 165-167TC

Value: 0.31 (silicone; cyclohexane / ethyl acetate_ = 1: 1) g W Μ 1 A

In-撖 乙 某 ¾ ¾ 某-2 (2.3.4.Fi-Eg-1H —-g ^ -fh ϋ »ϋ -7k 筘 物 410mg 4- [4- [2- (methoxy Carbonyl) ethyl] phenyl] -5-methyl-2-(3-trifluoroethylfluorenyl-2,3,4,5-tetrahydro-111-3-benzodiazepta-7-yl ) -4H-1,2,4-triazol-3-one with 10 ml of glacial acetic acid and 10 ml of semi-concentrated hydrochloric acid and stir at 901C for 7 hours. After cooling, the mixture is evaporated. The residue is stirred with water and evacuated. It was washed with water and acetone. Yield: 240 mg (57 ο of theoretical value, melting point: > 250¾ -100- This paper size is in accordance with Chinese Standard (CHS) A 4 (210X297 mm) ~ _ ( Please read the notes on the back before filling in. (This page). Binding. Printed by A6 B6_ 'of the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 5. Description of Invention (99)

Rf value: 0.43 (reverse phase silica gel; methanol / 5¾ saline solution = 6: 4) Theoretical value: C 59.12 Η 6.09 Ν 12.53 Cl 7.93 Experimental value: 58.96 6.13 12.31 7.74 The compound was prepared similarly to Example 14: (1 ) 1- [trans-4- (2-carboxyethyl) cyclohexyl] -3- (2,3,4,5-tetrahydro-1H-3-benzodiazine-7-yl) -tetra Hydroimidazol-2-one-hydrochloride Melting point: > 250Ό

Rf value: 0.46 (reverse phase silicone; methanol / 5¾ brine = 6: 4) Theoretical value: C 62.62 Η 7.64 Ν 9.98 Cl 8.40 Experimental value: 62.24 7.67 10.01 8.86 (2) 1- [Trans-4- (2- Carboxyethyl) cyclohexyl] -3- (1,2,3,4,5,6-hexahydro-3-benzodiazepine-8-yl) -tetrahydroimidazol-2-one-hydrogen atmosphere Compound (3) 2- [4- (2-carboxyethyl) phenyl] -4- (2,3,4,5-tetrahydro-lH-3-benzomonoazine-7-yl)- 4H-l, 2,4-triazole-3-hydrazone-hydrogenated compound (4) 4- [4- (2-carboxyethyl) phenyl] -5-phenyl-2- (2,3,4 , 5-tetrahydro-1H-3-benzotriazine-7-yl) -4fluorene-1,2,4-triazol-3-one-hydrochloride (5) 4- [4- (2_ Carboxyethyl) phenyl] -2- (2,3,4,5-tetrahydro-lH-3-benzodiazepine-7-yl) -5-trifluoromethyl-4H-1,2 , 4-triazole-3 -_- hydrochloride (6) [[4- (2-carboxyethyl) phenyl] -3- (2,3,4,5-tetrahydro-1H-3-benzene Pentazine-7-yl) -3,4,5,6 "tetrahydro-1H-pyrimidin-2-one-hydrogenated compound (7) 4- [4- (2-carboxyethyl) phenyl ] -5-ethyl-2- (2,3,4,5-tetrahydro-101-This paper uses Chinese National Standard (CNS) A4 specifications (210X 297 mm). {Please read the note on the back first Matters need to fill in this page). Binding. Economy Printed by A6 B6, Consumer Cooperatives of the Central Bureau of Standards. 5. Description of the invention (100) -1H-3-benzo-nitrogen-seven-garden-7-yl) -4H-1.2,4-triazole-3-hydrazone-hydrogenated compound (8) 5- [4- (2-carboxyethyl) phenyl] -4-methyl-2- (2,3,4,5-tetrahydro-1H-3-benzo-nitroazine-7 -Yl) -4Η-1,2,4-triazole-3- 醑 -hydrogenated compound (9) 4- [4- (2-carboxyethyl) phenyl] -3-methyl-1- (1 , 2,3,4-tetrahydroisoquinolin-6-yl) -tetrahydroimidazol-2-one-hydrogenated compound (10) 2- [trans-4- (2-carboxyethyl) cyclohexyl]- 4- (2,3,4,5-tetrahydro-111-3-benzotriazine-7-yl) -211,411-1,2,4-triazole-3,5-dione-hydrogen atmosphere Compound (11) 1- [3- (2-carboxyethyl) phenyl] -3- (2,3,4,5-tetrahydro-111-3-benzotriazine-7-yl)- Tetrahydroimidazol-2-one-hydrochloride (12) 1- [4- (fluorenylmethyl) benzyl] -3- (2,3,4,5-tetrahydro-1 (1-3-benzene Benzazine-7-yl) -tetrahydroimidazol-2-one-hydrochloride (13) 2- [trans- 4- (2-carboxyethyl) cyclohexyl] -5- (2,3, 4,5-tetrahydro-1H-3-benzodiazepine-7-yl) -3,4-dihydro-2H, 5H-thiadiazole-1,1 -dioxide value: 0.50 (reverse Phase silicone; methanol / 5¾ brine = 6: 4) (14) bu [4- (2-carboxy-1-octyl Phenyl] -3- (2,3,4,5-tetrahydro-1H-3-benzotriazine-7-yl) -tetrahydroimidazol-2-one-hydrochloride (15) 2- [Trans-4- (2-carboxyethyl) cyclohexyl] -4- (2., 3,4,5-tetrahydro-1H-3-benzodiazepine-7-yl) -1-form -211,411-1,2,4-triazole-3,5-dione-hydrochloride (16) 1- [4- (3-carboxypropyl) phenyl] -3- (2,3 , 4,5-Tetrahydro-111-3-benzene-102- This paper size is in accordance with China National Standard (CNS) A4 (210x297 mm) (Please read the precautions on the back before filling this page)- Binding. A6 B6 printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 5. Description of the Invention (101) Benzodinitrogen-7-based) -Tetramimine-2-one-Argonate (17) 1- ( 5-carboxypropyl) -3- (2,3,4,5-tetrahydro-1H-3-benzodiazepine-7-yl) -tetrahydrooxazol-2-one-hydrochloride ( 18) 1- [4- (2-carboxyethyl) -2-fluorobenzyl] -3- (2,3,4,5-tetrahydro-1H-3-benzylazine-7-yl ) -Tetrahydroimidazole-2-fluorene-hydrogen (19) 1- [4- (2-carboxyethyl) -3-methyl-phenyl] -3- (2,3,4,5-tetrahydro -1H-3-benzomonoazine-7-yl) -tetrahydrooxazol-2-one-hydrochloride (20) 1- [trans-4-[(carboxymethyl) oxy] cyclohexyl] -3- ( 2,3,4,5-tetrahydro-1H-3-benzodiazepine-7-yl) -tetrahydrooxazole-2-fluorene-hydrogenated compound Melting point: 316-317 it (decomposed)

Rf value: 0.6 6 (reverse phase silicone; methanol / 5S; saline solution = 6: 4) theoretical value: C 59.50 Η 7.13 Η 9.91 Cl 8.36 experimental value: 59.26 7.13 9.94 8.44 (21) Bu [4- (Trans-2 -Fluorenylethyl) phenyl] -3- (2,3,4,5-tetrahydro-1H-3 -benzobenzoazine-7-yl) -tetrahydroimidazol-2-one-hydrogen Ambient Rr value: 0,64 (reverse phase silicone; methanol / 5% brine = 6: 4) Mass spectrum: M + = 377 (22) l- [4- (2-fluorenyl-1-propyl) Benzoyl] -3- (2,3,4,5-tetraargine-1! 1-3-benzodiazepine-7-yl) -tetrakimidazol-2-fluorene-hydrogenated compound X H2〇

Rf value: 0.34 (reverse phase silicone; methanol / 5% saline solution = 6: 4) Theoretical value: C 61.66 Η 6.71 Η 9.38 Cl 7.91 Experimental value: 61.5 6 6.75 9.3 0 δ. 14 (2 3) 1- [Reverse -4- (2-Carboxyethyl) cyclohexyl] -3- (2,3,4,5-tetrahydro- -103- The standard of this paper is Chinese National Standard (CNS) A4 Specification (210X 297 mm ) ....................................... ................................................ ...... 玎 ................ {Please read the notes on the back before filling this page A6 B6 Central of the Ministry of Economy Printed by the Consumer Cooperatives of the Bureau of Standards V. Description of the invention (102) 1H-3-benzylazine-7-yl) -3H-dihydroimidazol-2-one-hydrogenated compound (2 4) 1- [ Trans-4- (2-carboxyethyl) cyclohexyl] -3- (2,3,4,5-tetrahydro-1H-2-benzotriazine-7-yl) -tetrahydrooxazole- 2-fluorene-hydrochloride (2 5) 2- [trans-4- (2-carboxyethyl) cyclohexyl] -4- (2,3,4,5-tetrahydro-1H-3-benzo-1 Nitrogen heptadecyl-7-yl) -4H-1,2,4-triazol-3-one-hydrogenated compound was used at a concentration of 2% hydrochloric acid and the compound of Example 18 (1) as a starting material. Melting &:> 220 1: Value: 0.50 (reverse-phase silicone; methanol / 5¾ brine = 6: 4) Theoretical value: C 59.92 Η 6.94 Ν 13.31 Cl 8.42 Experimental value: 60.03 6.99 13.32 8.46 (26) 2- [ Trans-4- (2-carboxyethyl) cyclohexyl] -4- (2,3,4,5-tetrahydro-1H-3-benzodiazepine-7-yl) -5-methyl- 4H-1,2,4-triazole-3- 嗣 •• hydrogenated compound (2 7) 2- [trans-4- (2-carboxyethyl) cyclohexyl] -4- (2, 3,4, 5-tetrahydro-1H-3-benzodiazepine-7-yl) -5-phenyl-4H-1,2,4-triazol-3-one-hydrochloride (28) 4- [ Trans-4- (2-carboxyethyl) cyclohexyl] -2- (2,3,4,5-tetrahydro-1H-3-benzo-nitroazine-7-yl) -4Η-1,2 , 4-Triazol-3-one-hydrochloride Melting point: > 240¾ Value: 0.64 (reverse phase silicone; methanol / 5¾ brine = 6: 4) (29) 4- [Trans-4- (2 -Carboxyethyl) cyclohexyl] -2- (2,3,4,5-tetrahydro- (Please read the precautions on the back before filling this page} -Packing, p. 'Embroidery. -104- This paper Standards are used in China National Standard (CNS) A4 specifications (210X297mm) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A6 B6 V. Description of the invention (1Q3) 1H-3-Benzodiazine 7-based ) -5-methyl-4H-1,2,4-tri -3- _ - hydrogen atmosphere thereof

Rf value: 0.48 (reverse phase silicone; formazan / 5! «Brine solution = 6: 4) Theoretical value: C 60.75 Η 7.18 Η 12.88 Cl 8.15 Experimental value: 60.54 7.26 12.68 8.54 (30) 4- [Trans-4- (2-carboxyethyl) cyclohexyl] -2- (2,3,4,5-tetrahydro-1H-3-benzylazine-7-yl) -5-phenyl-4H-1, 2,4-triazol-3-one-hydrogenated compound (31) _1- [4- (2-carboxy-1-phenyl-ethyl) phenyl] -3- (2,3,4,5- Tetrahydro-1 fluorene-3-benzodiazine-7-yl) -tetrahydroimidazol-2-one-hydrogenated compound

Rf value: 0.31 (reverse phase silica gel; methanol / 5¾ brine = 6: 4) (32) 1- [1- (2-carboxyethyl) hexahydropyridin-4-yl] -3- (2,3, 4,5-tetrahydro-1H-3-benzo-1a-7-yl) -tetrahydroimidazol-2-one-hydrochloride (33) 1- (trans-4-carboxycyclohexyl) -3 -[2- (2,3,4,5-tetrahydro-1H-3-benzodiazepine-7-yl) ethyl] -tetrahydroimidazole- 2 -_- hydrochloride (34M- [ 2- (4-Carboxybenzyl) ethyl] -3- (2,3,4,5-tetrahydro-111-3-benzodiazepine-7-yl) -tetrahydroimidazol-2-one -Hydrogenated atmosphere X H2O value: 0.40 (reverse phase silica gel; methanol / 5¾ brine = 6: 4) Mass spectrum: M + = 379 Theoretical value: C 60.89 Η 6.50 Η 9.68 Cl 8.17 Experimental value: 60.57 6.62 9.77 8.22 Example 1 5 4-"4-" 2- (Using argon, carbonyl), E, 1, 1,2, 1-5,-Shen, -2- (3-Tri-argon, acetyl-, -2.3.4.5-Tetra-argon-1 Only -3- Mo # 一 氪 十 圈 -7-a) -4 > 1- -105- The standard of this paper is Chinese national standard (CNST ^ i gas grid (210X 297mm)) (Please read the back Please fill out this page again)-Binding A6 B6 printed by the Employees' Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (104) 1 · 2.4--Turn over 1.6 grams of 7-iodine-3-trifluoro Ether group-2,3,4,5-tetrahydro-lH-3-benzodiazepine, 11 g 4- [4- [2- (methoxycarboxy) -ethyl] phenyl] -5 -Methyl-4H-1,2,4-triazole-3-hydrazone, 0.19 ml of tri- [2- (2-methoxyethoxy) -ethyl] -amine, 130 mg of affluent cuprous, 130 mg of cuprous iodide and 1.1 g of potassium carbonate were refluxed in 30 ml of dimethylformamide for 2 hours. After cooling * the mixture was evaporated and the residue was separated between water and dichloromethane. The solid was filtered by suction It is separated by calendar, washed with water, dehydrated, extinguished and evaporated. The residue K chromatography is purified in a silica gel column using cyclohexane / ethyl acetate = 1: 1. Yield: 340 mg (the theoretical value of 16¾ ),

Melting point: 160-162 ° C Value: 0.51 (silicone; cyclohexane / ethyl acetate = 1: 1) The compound was prepared from analogous to Example 15 at (1) 4- [trans-4- [2- ( Methoxycarbonyl) ethyl] cyclohexyl] -2- (3-trifluoroethylfluorenyl-2,3,4,5-tetrahydro-1H-3-benzyl-7-yl)- 5-methyl_4Η ~ · 1,2,4_trisleep-3-嗣 Melting point: 175-177Ό Value: 0.50 (silicone; dichloromethane / ethyl acetate = 90:10) (2) 4- [Reverse -4- [2- (methoxycarbonyl) ethyl] cyclohexyl] -2- (3-trifluoroethylfluorenyl-2,3,4,5-tetrahydro-1H-3-benzo-nitrogen t Circle-7-based > -M-fluorene, 2,4-triazole-3-fluorene

Rf value: 0,40 (silicone · * dichloromethane / methanol = 100: 1)

Cellar Li 1 R -106- This paper size is selected from the national standard (CNS) A4 size (210 X 297 mm) of the country .............. ..... Order ..........., {Please read the notes on the back before filling in this page} Consumption of shellfish by the Central Standards Bureau of the Ministry of Economic Affairs Printed by the cooperative A6 ____ B6___ V. Description of the invention (105) 1- "ji-4-Γ2- (a gas, a carbonyl, a) B; BM means R, a ΜΙ», a -2.3.4.5-four gas-111-3- Benzo-Helium 10--7) -Linconium is shown in 4.1 g (3-trifluoroethylglycosyl-2,3,4,5-tetrahydro-1H-3-benzo-nitroazine garden-7 -Yl) -isocyanate and 3.7 g of [[trans-4- [2- (methoxycarbonyl) -ethyl] cyclohexyl] amino] -methyl acetate-hydrogenate in 50 ml of acetonitrile and 3.2 ml of N -Ethyl-diisopropylamine and the mixture were stirred at room temperature for 2 1/2 days. After the reaction solution was evaporated, the residue was extracted with ethyl acetate and washed with water and brine. The organics were dehydrated and evaporated and Although the residue M is small, the methanol is recrystallized in an ice bath. The product is filtered through suction, washed with cold formic acid, and dried. Yield: 4.1 g (56S!), Melting point: 118-120t:

Rf value: 0.85 (silicone; ethyl acetate) g Example 1 7 1- "trans-4-" 2- (star propyl argon 镅 Ί 擐 Ί 擐 Ί 擐 R 某 even -2.3.4.5-tetrahydro-: ^ -3-pyridine, one round, ten rounds, 7-some) -tetraargon, -9-fluorene-fi gas, 230 mg 1- [trans-4- [2- (isopropoxycarbonyl) ethyl ] Cyclohexyl] -3-(3-propenyl-2,3,4,5-tetrahydro-111-3-benzotriazine-7-yl) -tetrahydrooxazole-2-fluorene-hydrogen Chloride was hydrogenated in 10 ml isopropanol at 30¾ and 50 psi argon in the presence of 50 mg of 10J! Pd / C for 6 hours. The catalyst was filtered by suction and the filtrate was evaporated. Yield: 240 mg,

Rf value: 0.55 (silicone; methane / methanol / concentrated ammonia = 95: 5: 1) -107- For the 4L scale, use China National Standard (CNS) A4 (210 X 297 mm) (谙 先Read the notes on the back and fill in this page) .0 · " ·· Classes · Printed by A6 B6 of the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (106) Fen M 1 8 2-"Anti-4 -"2- (Shen arg, y, y, y), 7, y, 1, y, 1-5-0, trisyl glycosyl-2.3.4.5-tetragas-1 ^-荣 # 一气 十 圆 -7-some)- 3.4-Difluorene-211..1 ^ -1.2.5-pyrodi-11-diargonide in 1.25 g of 2- (3-trifluoroethylfluorenyl-2,3,4,5-tetrahydro-1fluoride -3-Benzodiazepine-7-yl) -3,4-dihydro-2H, 5H-1, 2,5-thiadiazole-1,1-dioxide, 0.64 g of 3- (cis -4-Hydroxycyclohexyl) methyl propionate [Rf value: 0.58 g (silica gel; cyclohexane / ethyl acetate = 1: 1); Cyclohexane was used in a silica gel column for cis / trans mixture M chromatography Hexane / ethyl acetate (1: 1)] and 0.990 g of triphenylphosphine in 2 ml of ethyl acetate, 0.54 ml of diethyl azodicarboxylate was added, and 1.5 g of 3- (cis-4- Hydroxycyclohexyl) methyl propionate and 0.90 g of triphenylphosphine and 0.5 4 ml of azo A mixture of diethyl formate in 2 ml of acetonitrile. After stirring at room temperature for 30 minutes, a mixture of 0.90 g of triphenylphosphine and 0.54 ml of diethyl azodicarboxylate was added again. Stir overnight at room temperature. After that, the mixture was evaporated and the residue was chromatographed on a silica gel column using cyclohexane / ethyl acetate / dichloromethane (1: 1: 1). Yield: 700 mg (3850, theoretical value,

Melting point: 16 9 -17 3 1C

Rf value: 0.61 (silicone; cyclohexane / ethyl acetate / dichloromethane = 1: 1: 1) The compound was prepared from analogous to Example 18: (1) 2- [trans-4- [2- ( Methoxycarbonyl) ethyl] cyclohexyl] -4- (3-third-butoxycarbonyl-2,3,4,5-tetrahydro-111-3-benzodiazepine-7-yl) -1 0 8 — This paper size uses Chinese National Standard (CNS) A4 specifications (210X297 mm) (Please read the precautions on the back before filling out this page)-Binding. Printed by the Staff Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Preparation A6 ____B6_____ V. Description of the invention (107) 4H-1,2,4-triazole-3- 髑 Melting point: 162-164Ό

Rr value: 0.43 (silicone; hexane / ethyl acetate / dichloromethane = 1: 1: 1)

Window window 1 Q 1- "trans-4- (2- 撖 a certain Bum) 顼 hexyl 1-3-U • Tianmou four Μ -ΙΗ-3- cage # 一 Portuguese + Pu-7-some 1-4 Argon-9-face-¾ short servant in 5.0 g of 1- [trans-4- (2-carboxyethyl) cyclohexyl] -3- (2,3,4,5-tetrahydro-1H-3 -Benzotriazine-7-yl) -tetrahydroimidazol-2-one-hydrogenate, 4.5 ml of formic acid, 3.6 ml of 37X aqueous formaldehyde, and 20 ml of a mixture were added with 2.0 g of sodium hydrogen carbonate * Ice-cooled, and then the mixture was heated to 65 T. After cooling for 8 hours, stirred overnight and the mixture was evaporated. The residue K water was stirred and evaporated again. Then the residue M water was stirred again and adjusted to pH 1 with hydrochloric acid. After evaporation, the residue was stirred with a small amount of water and filtered with suction. The filter cake was stirred with K acetone, and the product was filtered with suction, washed with K acetone, and dried under vacuum. Yield: 3.7 g (7U of theory), Melting point: 292-295t: (Decomposition) 1 value: 0.38 (reverse phase silicone; methanol / 5¾ brine = 6: 4). The compound under K was prepared similarly to Example 19: (1) 1- [trans-4-[(carboxymethyl) Oxy] cyclohexyl] -3- (3-methyl-2,3,4,5-tetrahydro-111-3-benzo-nitroazine-7-yl) -tetrahydro -2-one - hydrochloride xNaClx0.5H20

Rf value: 0.62 (reverse-phase silicone; methanol / 5¾ brine = 6: 4) -109- This paper size is used in 8 countries (CNS) A4 specification (210X297 mm) ~~~ (Please read first Note on the back, please fill out this page again.} • Equipment: Tr-Embroidery. • -W- A6 _B6 _ V. Description of the invention (108) ′ * l Theoretical value: C 52.28 Η 6.58 Η 8.31 Cl 13.49 Experimental value: 52.28 6.58 8.33 14.03 (2) 1- [4- (2-Postyl-1-propene..yl) phenyl] -3-. (3-methyl-2,3,4,5-tetrahydro- 1H-3-Benzodiazepine-7-yl) -tetrahydroimidazol-2-one-hydrogenated compound X 0.5 H2 0 ', 1 ^ value: 0 · 29 (reverse phase silicone; methanol / 5¾ saline solution = 6: 4) Theoretical value: C 63.63 Η 6.90 Ν 9.28 Cl 7.83 Experimental value: 63.32 6.99 9.32 7.81, (3) 3- [trans-4- (2-fluorenylethyl) cyclohexyl] -1- (3 -Methyl-2,3,4,5 -tetrahydro-1H-3-benzylazine-7-yl) -Allantoin-Hydrogenide Melting point:> 250Ό Value: 0.32 (reverse phase silicone; Methanol / 5¾ brine = 6: 4) Theoretical value: C 61.39 Η 7.17 Ν 9.34 Cl 7.8 8 Experimental value: 61.39 7.25 9.37 7.92 (4) 1- [trans-4- (2-carboxyethyl) cyclohexyl]- 3- (3-methyl-2,3,4,5 -tetrahydro-1H-3-benzo-nitroazine-7- ) - allantoin - hydrochloride

Rf value: 0.37 (silicone; methane / methanol / concentrated ammonia water = 80: 20: 2) Theoretical value: C 61.39 Η 7.17 Η 9.34 Cl 7.88 Experimental value: 61.11 '7.26 9.36 7.86 Employees of the Central Standards Bureau of the Ministry of Economic Affairs Printed by Consumer Cooperatives (Please read the precautions on the back before filling out this page) (5) 2- [Trans- 4- (2-carboxyethyl) cyclohexyl] -4- (3-methyl-2,3, 4,5-tetrahydro-111-3-benzotriazine-7-yl) -1-methyl ^ -211,411-1,2,4-triazole-3,5-dione-hydrogenated compound ( 6) 2- [trans-4- (2-carboxyethyl) cyclohexyl] -4- (3-methyl-2,3,4,5 -110- This paper size applies to China National Standard (CNS) A4 Specifications (210X297 mm) ___ B6 _ V. Description of the invention (109)

-Tetrapyrene-1H-3-benzo-nitrogen t--7-yl > -4 pyrene-1,2,4-triazol-3-one-hydrogenated compound Melting point: > 220TC

Rr value: 0.48 (reverse phase silicone; formazan / 5 *! Saline solution = 6: 4) Theoretical value: C 58.10 Η 7.36 Η 12.32 Cl 7.80 Experimental value: 58.07 7.36 12.28 7.83 (7) 2- [Trans-4- (2-Carboxyethyl) cyclohexyl] -4- (3-methyl-2,3,4,5-tetrahydro-1H-3-benzo-nitrogen if-7-yl) -5-methyl -4H-1,2,4-triazol-3-one-hydrogenated compound (8) 2- [transM- (2-carboxyethyl) cyclohexyl] -4- (3-methyl-2,3 , 4,5 -tetrahydro-1H-3-benzodiazepine-7-yl) -5-phenyl-4H-1,2,4-triazol-3-one-hydrogenated compound (9) 4- [trans-4- (2-carboxyethyl) cyclohexyl] -2- (3-methyl-2,3,4,5 -tetrahydro-1H-3-benzomonoazine seven group-7- ) -4Η-1,2,4-triazole- 3 -_- hydrochloride (10) 4- [trans- 4- (2-carboxyethyl) cyclohexyl] -2- (3-methyl- 2,3,4,5 -tetrahydro-1H-3-benzodiazepine-7-yl) -5-methyl-4H-1,2,4-triazol-3-one X 1.1 HC1 x0 .2H20 Melting point: 238-24〇υ

Rf value: 0.37 (reverse phase silicone; methanol / 5¾ brine = 6: 4) Theoretical value: C 60.55 H7.40 N 12.28 C1 8.5 5 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back first) Fill out this page again.) Experimental values: 60.68 7.53 12.31 8.36 (11) 4- [trans- 4- (2-carboxyethyl) cyclohexyl] -2- (3-methyl-2,3,4,5- Siqi-1H-3-benzyl-1N-7-yl) -5 -phenyl-4H-1,2,4-trisialol-111-This paper uses National Standard (CNS) A 4 Specifications (210x297 mm) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A6 B6__ V. Description of the Invention (11 (D) -3-keto-hydrogenated compound (12) 1- [trans-4- (2-carboxyl Ethyl) cyclohexyl] -3- (3-methyl-2,3,4,5-tetrahydro-1H-3-benzylazine-7-yl) -3,4,5,6- Tetra-111-pyrimidin-2-one X 1.05 HC1 χθ.3 H2 0 Melting point: 237-240¾. Value: 0.37 (reverse phase silicone; methanol / 5X saline solution = 6: 4) Theoretical value: C 63.04 Η 8.07 Ν 9.18 Cl 8.14 Experimental value: 62.97 8.05 9.15 8.16 (13) [4- (2-carboxy-; 1-phenyl-ethyl) phenyl] -3- (3-methyl-2,3, 4.5- tetra Hydrogen-11! -3-benzo-nitroazine-7-yl) -tetrahydroimidazole-2- _-Hydronitride (14) 1- [1- (2-carboxyethyl) hexahydropyridin-4-yl] -3- (3-methyl-2, 3.4.5- tetrahydro-: ^-3 -Benzobenzoazine-7-yl) -tetrahydroimidazol-2-one-hydrochloride (15) 1- (trans-4-carboxycyclohexyl) -3- [2- (3-methyl- 2,3,4,5-tetrahydro-1H-3-benzodiazine-7-yl) ethyl] -tetrahydroimidazol-2-one-hydrochloride (16) Bu [2- (4 -Carboxyphenyl) ethyl] -3- (3-methyl-2,3,4,5-tetrahydro-1H-3-benzodiazepine-7-yl) -tetrahydrooxazole-2 -Keto-hydrogenated compound (17) 1- [trans-4- (2-carboxyethyl) cyclohexyl) -3- (7-methyl-6,7,8,9 -tetrahydro-5H-pyrimido [4: 5-01] —Nitrazine-2-yl) tetrahydroimidazol-2-one-hydrogenated compound 1 ^ value: 0.56 (reverse phase silicone; methanol / 5¾ toilet solution = 6: 4) Mass spectrum ： M + = 401 / -112- This paper size adopts China National Standard (CNS) A4 specification (210X297mm) (Please read the precautions on the back before filling this page)-Binding: Central Standard of the Ministry of Economic Affairs Printed by the Consumer Cooperative of the Bureau A6 B6 V. Description of the invention (111) (18) 1- [trans-4- (2-carboxyethyl) cyclohexyl) -3- (7-methyl-6,7,8, 9-tetrahydro-5H-pyracino [2,3-d] —nitrosepta-2-yl) tetra Imidazol-2-one-hydrogenated compound (19) 1- [trans-4- (2-carboxyethyl) cyclohexyl) -3- (7-methyl-6,7,8,9 -tetrahydro-5H -Pyrido [2,3-d] —aza-seven-2-yl) tetrahydrooxazole-2- _hydrogenated compound (20) 1- [trans-4- (2-carboxyethyl) cyclohexyl] -3- (2-methyl-1,2,3,4-tetrahydro-isoquinolin-6-yl) -tetrahydroimidazole-2-fluorene-hydrogenated compound (21) 1- [trans-4- (2-Carboxyethyl) cyclohexyl] -3- (2-methyl-2,3,4,5 -tetrahydro-1H-3-benzomonoazine-7-yl) -tetrahydroimidazole- 2-keto-hydrogenated compound (22) 1- [trans-4- (2-carboxyethyl) cyclohexyl] -3- (3-methyl-1,2,3, 4.5,6-fluorenhydro-3 -Benzotriazol-8-yl) -tetrahydroimidazol-2-one-hydrochloride (23) 2- [trans-4- (2-fluorenylethyl) cyclohexyl] -4- (3 -Methyl-2,3,4,5-tetrahydro-1H-3-benzomonoazine-7-yl) -2Η, 4Η-1,2,4-triazole-3.5-dione-hydrogen Example of chloride bleaching 2 0 1-M-7, some ... tetra-argon-1H-: ¾-cage well-one M ten W-7-some) Ί "4-" 2- (g argon some 镅) ¾¾-tetraargon ll ¢ -2-aa 600 mg 1- [4- [2- (methoxycarbonyl) ethyl] phenyl] -3-(2,3, 4,5-tetrahydro-111 -3-Benzotriazine-7-yl) -tetrahydroxazol-2-one-hydrogenated compound and 128 mM Sodium hydride (55¾ in paraffin oil) was treated in 15 ml of dimethylformamide in an ultrasonic bath for 2.5 hours. Add 125 microliters -113- This paper uses Chinese National Standard (CNS) A4 specifications (210X297 mm) (please read the precautions on the back before filling this page)-binding, ordering. Printed by the Industrial and Consumer Cooperatives A6 ___ B6_____ V. Description of the invention (112) Ethyl iodide and the mixed solution are processed for another 2.5 hours. The reaction solution was combined with 50 ml of water, and the forging was passed through oil and gas, washed with water and dried. Crude product M is analyzed by silica gel column using dichloromethane / formaldehyde / concentrated ammonia (9: 1: 0.1). 0 Yield: 260 g (44¾ of theory)

Melting point: 168-170T R *. Value: 0.45 (silicone; methane / methanol / concentrated ammonia = 4: 1: 0.2) The compound was prepared from similar to Example 20: (1) 1- (3-butyl -2,3,4,5-tetrahydro-1fluorene-3-benzodiazepine-7-yl) -3- [4- [2- (methoxycarbonyl) ethyl] phenyl] -tetra Hydroimidazol-2-one value: 0.64 (silicone; diazomethane / methanol / concentrated ammonia = 4: 1: 0.2) (2) 1- [trans-4- [2- (isopropoxycarbonyl) ethyl] Cyclohexyl] -3- (3-propenyl-2,3,4,5-tetrahydro-111-3-benzotriazine-7-yl) -tetrahydroimidazol-2-one-hydronitride Bromopropene / N-ethyldiisopropylamine was performed in acetonitrile. 1 ^ value: 0.63 (silicone; methane / formaldehyde / concentrated ammonia = 95: 5: 1) (3) 1- [trans-4- [2- (methoxycarbonyl) ethyl] cyclohexyl]- 3- (3-benzyl-2,3,4,5-tetrahydro-11 ^ 3-benzo-1.azine-7-yl) -tetrahydrooxazol-2-one-hydrochloride value: 0.30 (silicone; dichloromethane / methanol = 95: 5) (4) 1- [trans-4- [2-(methoxycarbonyl) ethyl] cyclohexyl] -3- [3- (cyclopropyl-114 —: This paper size is used _ China National Standards (CNS) A4 specifications (210X297 mm) {Please read the notes on the back to complete this page). Install, order, and staff consumer cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs Printed _B6__ V. Description of the Invention (113) methylmethyl) -2,3,4,5-tetrahydro-1H-3-benzodiazepine-7-yl) -tetrahydroimidazol-2-one -Hydrogenated acetonitrile and cyclopropylmethyl bromide are used in the presence of sodium iodide and N-ethyldiisopropylamine. Melting point: 225-230 ¾ (decomposed)

Rr value: 0.72 (silicone; methane / methanol / concentrated ammonia = 90: 10: 2) (5) 1- [trans-4- [2- (methoxycarbonyl) ethyl] cyclohexyl] -3- [3- (2-hydroxyethyl) -2,3,4,5 -tetrahydro-1H-3 -benzobenzoazine-7-yl) -tetrahydroimidazol-2-one-hydroiodide acetonitrile And 2-bromoethanol are used in the presence of sodium iodide and N-ethyldiisopropylamine. Melting point: > 200 t:

Rf value: 0.55 (silicone; methane / methanol / concentrated ammonia = 90: 10: 2) (6) [[trans-4- [2-(methoxycarbonyl) ethyl] cyclohexyl] -3-[ 3- (methoxycarbonylmethyl) -2,3,4,5-tetrahydro-1b 3-benzodiazepine-7-yl) -tetrakimidazol-2-oneacetonitrile and 2-bromo Methyl acetate is used in the presence of sodium iodide and N-ethyldiisopropylamine to fractally extract the free base. Melting point: 127-129¾ Value: 0.28 (reverse phase silica gel; methanol / 5¾ saline solution = 6: 4) nmm 2λ 3-"trans-4-" 2- (methyl argon carbonyl certain 1 某 R group 1-1-1 (2.3.4.5-IV-115- National Standard (CNS) A4 specifications for this paper size (210 (Please read the precautions on the back before filling in this page)-Binding. A6 B6 V. Invention Description U4 ) (Please read the notes on the back before filling this page)

ff-in Cangyou a short ten garden-7- < nM 蠹 素-«« Wound I ammonium chloride gas flow 920 g g 3- [trans_4- [2- (methoxycarbonyl) ethyl] -Cyclohexyl] -1- (3-trifluoroethylfluorenyl-2,3,4,5-tetrahydro-lH-3-benzodiazepine-7-yl)-allantoin in 5 () The mixture was decanted for 10 minutes and the mixture was refluxed for 5 hours. After cooling, the product is pumped through 滹, washed with formic acid and ethyl ether and dried at 80 t: dry refining. Yield: 770 mg (95¾ of theory) Melting point: > 250t: Value: 0.23 (reverse-phase silicone; methanol / 53 liters of saline solution = 6: 4) The compound under κ was prepared similarly to Example 21: -pack (1) 1- [trans-4- [2- (methoxycarbonyl) ethyl] cyclohexyl] -3- (2,3,4, 5-tetrahydro-1H-3-benzomonoazine-7- Base) -Allantoin-Hydrogenate Melting point: > 2 5 0 t: Value: 0.43 (reverse phase silicone; formazan / 5¾ saline solution = 6: 4) Theoretical value: C 61.39 Η 7.17 Ν 9.34 Cl 7.88 Experiment Value: 61.10 7.21 9.29 8.03 (2) 1- [trans-4- [2- (methoxycarbonyl) ethyl] cyclohexyl] -3- (2,3,4, 5-tetrahydro-111-3- Benzoazine-7-yl) -3,4,5,6-tetrahydro-1 {1-pyrimidine-2-hydrazone-hydrochloride

Rf value: 0.31 (reverse phase silicone; methanol / 5 »; saline solution = 6: 4) nm?? 3-" trans-4- "2- (methyl hydrogen carbonyl) π even -1-The central standard of the Ministry of Health of the PR of China, Beige Consumer Cooperative Co., Ltd.-2.3.4 · 5-tetrahydro-1Η-3-cage and one argon ten 酾 -7-urine 40mg third butoxide Added to 2.1 grams of NR- [trans-4- [2- (methoxyl 116) This paper is in the national standard (CNS) A4 specification (210X297 mm). Printed by the Bayer Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs. Preparation of A6 B6 _ 5. Description of the invention f15) carbonyl) ethyl] -cyclohexyl] -fluorene '-[(benzyloxycarbonyl) methyl] -N'-(3-trifluoroethylfluorenyl-2,3, 4,5-tetra-argon-1, 3-benzo-nitroazine, 7-yl) -gland in 25 liters of boiling carbamidine, and the mixed solution was passed through a wine stream for 30 minutes. After the reaction solution was cooled * and A few drops of sorbic acid were stirred, evaporated and decanted in a silica gel column using cyclohexane / ethyl acetate (8: 2 to 7: 3), purified and recrystallized from formazan fermentation. 0.95 g (Theoretical value of 55X), Melting point: 132-134TC IU value: 0.59 (Silicon; cyclohexane / ethyl acetate _ = 1: 1) g Example H 1-Γ trans-4-Γ2- [Tian arg some 镛So so 1 顼 R so Tetrapyrene; ^ -furidine # "4.5-41-value Shipu-2-a)-Tetrapyrene-?-Face 1.0 g 1- [trans-4- [2- (methoxycarbonyl) ethyl Group] -cyclohexyl] -3- (7-benzyl-6,7,8,9-tetrahydro-5 {1-pyrimidine [4,5- (1] -azaheptyl-2-yl) -3Η -Dihydroimidazol-2-one was hydrogenated in 15 ml of methanol at 500 mg Pd / C (10¾ platinum) at room temperature and 50 psi hydrogen pressure for 17 hours. The catalyst was filtered off and the filtrate was evaporated. The residue was directly used K Compound 0 in Preparation Example 9 (16) Value: 0.44 (reverse phase silicone; methanol / 5SK 麴 water = 6: 4) The compound under K was prepared similarly to Example 23: (1) 1- [Trans-4- [2- (methoxycarbonyl) ethyl] cyclohexyl] -3- (6,7,8, 9 -tetrahydro-5H -pyridine [2,3-d] -azaheptad-2-yl)- Tetrahydroimidazol-2-one hydrogen odorant nmm? Λ (Please read the precautions on the back before filling in this page) * Binding. -117- This paper is a standard of China National Standard (CNS) A4 (210X_297) (Mm) A6 B6 V. Description of the invention f16) 1-Γ2- (7, argon excites a certain 1- 2- "4- (3-a certain a-2.3.4.5-four gas-Siyuan-7-a certain) cage Even 1-tetramidine-2-one 3.1 g (3-methyl-2,3,4,5-tetrahydro-1H-3-benzylazine-7-group)-acid, 4.1 g of [2- (ethoxycarbonyl) sulfo_oxy) phenyl] -tetrahydroimidazole-2-fluorene, platinum) and 6.5 liters of triethylamine in 25 ml of two 100 100: lower ΐ Mix for 4 hours. After the reaction solution was cooled, the residue was dissolved in dichloromethane. The mixture was purified by silica gel column chromatography (100: 7) with silica gel and the resulting residue. Yield: 2.7 g (63¾ of theoretical value), Rr value: 0,31 (silicone; dichloromethane / methanol when Denglun example 2 5 · Contains 2.5 millimeters and 2.5 gram Beijing Wishes_Shui'an Ethyl]- 3- [4- (Trifluoromethyl 3.5 g tetrakis (triphenylphosphinemethylformamidine) is evaporated under nitrogen and vacuum, and the resulting solution is filtered, and the filtrate hydrocarbon is evaporated. Dichloromethane / formaldehyde 100: 7) M {Please read the precautions on the back before filling this page) • Binding. Printed by the Central Bureau of Standards X. Consumer Cooperative 2.5 mg 50.0 g 1.0 ml Sister: Active substance Mannase plus _water M Injection Preparation: Active Substances and mannitol are dissolved in water. The solution is transferred to amphibians and freeze-dried. When in use, the solution is prepared with water for injection. When Example 2 fi contains rhenium 2 milligrams and 35 milligrams live物 物 西 夕 铖 Tamped ampoule 118 This paper size uses Chinese National Standard (CNS) A4 specifications (.210 X 297 mm) A6 B6 V. Description of the invention (117) Sister: 35.0 mg 100.0 mg 2.0 ml { Please read the notes on the back before filling this page} Active substance mannitol plus _water M injection preparation: Active substance and After fermentation Lu dissolved in water. The solution was transferred to an ampoule OilPainting which * "• Lan The solution was washed with water in use to the freeze-dried injection Κ suspected. Li-rich perish 27

佥 .R0 Quaker live birch 1 SH SH. Pretend to be: (1) 50.0 g of active substance (2) 98.0 g of lactose (3 > 50.0 g of corn starch) (4) 15.0 g of polyvinylpyrrolidone Gram (5) Magnesium stearate 2.0 Prog 215.0 g Preparation: Printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (1 >, (2) and (3) mixed together and granular with the aqueous solution of (4) Add (5) to dry granules. Since then, the mixture is made into compressed tablets with bi-planar, double-sided, and indentations on one side. Tablet diameter: 9 mm 28 Contains 350 liters of Beijing birch chain -119- This paper is designed to meet national standards (CNS) A4 specifications (210X297 mm) 350.0 mg 136.0 mg 80.0 mg 30.0 mg 4.0 ¾ ¾ Central Standard of the Ministry of Economic Affairs Printed by the Consumer Cooperative of the Bureau A6 B6 V. Description of the invention (118) Sister-in-law: (1) Active substance (2) Lactose (3) Corn starch (4) Polyvinyl pyrrolidone (5) Preparation of magnesium stearate 600.0 mg : (1), (2) and (3) are mixed together and granulated with the aqueous solution of (4). Add (5) to the dry granules. The tablet has two sides? I plane, double side, and indentation on one side. The diameter of the tablet: 12 mm. When the example 29 contains 10 ¾ competing living creatures II: (1 ) Active substance 50.0 mg (2) Anhydrous corn starch 58.0 mg (3) Powdered lactose 50.0 g (4) Magnesium stearate 2.0 mg 160.0 g g Preparation: (1) and (3)-same mashing. This mashing The crushed material is added to the mixture of (2) and (4) with the bottom of the mixture. The powder mixture is filled in a capsule-filled container with No. 3 hard gelatin. Round 120 paper size. ) 肀 4 specifications (210X297mm): (Please read the precautions on the back before filling this page)

35.0 mg 46.0 mg 30.0 mg 4.0¾¾ 43 0.0 mg A6 B6 V. Description of the invention (119) Capsule. Example of window degradation? Ω Contains: Live-birth of the living animal Xi Xi Li Xiu Cheng: (1) Active substance (2) Anhydrous corn starch (3) Powdered lactose (4) Preparation of magnesium stearate: (1) and (3) — Same as mashing. This mash is added to the mixture of (2) and (4) with thorough mixing. This powder mixture was filled in a capsule-filling machine into a # 0 hard gelatin oval capsule. (Please read the notes on the back before filling this page)-Binding Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs -121-This paper uses the Chinese National Standard (CNS) A4 specification (210X297 mm)

Claims (1)

芎. S3101259 patent application case A8 a B8 Chinese Φ Please amend the scope of patent too (March 86) C8 D8 Continue to ask members to indicate whether the original substantive internal reference will be changed after the revision of the 4V case. Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs. Patent production. I. Cyclic derivative of formula (I) X γ ω (Where: X is not slender, S, Y represents CH 2 C .H 2, (: H = C 、, CH 2 C 0 or C 0 C Η 2 group, or optionally K. methyl-substituted C Η = Ν or N = C Η group; R a represents A-Β group preferably Φ, X * A represents one of the following formula ΓΓν ^ Ν 14 (CH --------- Ti ---- / 'ί (Please read the precautions on the back before filling out this page) CH 2 CH 2 C 1 to 2 sessions of methine in the benzo part of the nitrogen can be K nitrogen -1 This paper size applies to the Chinese National Standard (CNS) A4 specifications (210 X 297 mm) A8 B8 C8 D8 6. Application for patent scope Atom replacement, U 1 Swallowing " mirror or nail polish, R 4 represents hydrogen atom, cyclopropyl- or cyclopropylmethyl, C 1 -β-alkyl or allyl \ hydroxyalkyl, carboxyalkyl, alkane Oxycarbonylalkyl or benzyl >-R 1 · 4 represents S _ proto ~~ -or-combination * and τι represent numbers 1 or 2, and Β: cannot be swallowed ~ • Mirror > i 1 means The group of the formula F-E-D-wherein D represents a phenyl group or a cyclohexyl group, or a hexahydropyridyl group, wherein the ring nitrogen atom and the E group optionally replace the straight alkylene bond. , R represents a straight alkylene group, which may be substituted by a K alkyl group or a fluorenyl group, C 2-4 _ dilute alkylene group, or E may represent a straight chain linking the -D group via an oxygen atom .. 0-Employees of Central Standards Bureau Printed by Fei Cooperative (please read the notes on the back before filling out this page) F means M-hydroxy or Ca-e-alkoxy substituted ape: radical 'However, unless otherwise specified, the above-mentioned alkyl and alkylene Or the alkoxy moiety may each have 1 to 4 carbon atoms and each carbon atom on the above-mentioned fluorenyl and cycloalkyl moieties is bonded to at most 1 heteroatom; broad and p-isomers, stereoisomers And its salts C. 2 · Cyclopramidine derivatives of formula (ί) according to item 1 of the scope of patent application, in which the paper size applies the Chinese National Standard (CNS) A4 specification (210 × 297 mm) A8 B8 C8 D8 6. The scope of the patent application X represents a carbonyl group; Y represents CH 2 C Η 2, CH = C Η, CH 2 C 0-,-C 0 C Η 2-,-C Η di N-or 4 = CH- group, Each group is optionally substituted by a methyl group; "the group represents the AB group, of which A. Hebrew Among them, one to two in the benzo part of the above group. Each methine group can be replaced by nitrogen atom, G __ represents a bond or a methyl group, anti-barbine ® original ten "Ci-4_ comprehensive Printed on the basis of the basic, dilute alley, cyclopropane, or basic, and the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling out this page) η represents the number 1, and B represents a one-button Rb group means the following formula: F-E-D-Among them--This paper size is applicable to Chinese National Standard (CNS) A4 specification (210X297 mm) Αδ S84286 S D8 6. Scope of patent application (please read first Note on the back page, please fill in this page again) S means 1,4-dioxane or 1,4-cyclohexyl, or 1,4-hexahydropyridyl, which is the ring nitrogen atom and the case. Straight chain-dd- linkage of E group substituted with methyl or phenyl group, / E sound_indicates CH2CH2 group substituted with methyl or phenyl group, CH = CH or 〇-CH2 group * where 〇-CH2. The oxygen atom of the radical is connected to the radical D, and F represents a hydroxy group substituted by a hydroxy or C t A -alkoxy group, and tautomers, stereoisomers, and salts thereof. . 3. The compound of formula (I) according to item 1 of the scope of patent application, which is: U) 1- [4- [2- (methoxycarbonyl) ethyl] phenyl] -3- (1,2, 3, .4-tetrahydroisoxolin-6-yl) -tetrachlorooxazole-2 -fluorene, 1 b '丨 1-[4-2 -carboxyethyl) cyl] -3-(1, 2 , 3, 4-tetrahydroisoquinolin-6-yl) -tetrahydrooxazole-2 -one, U)].-[4-(2 -carboxyethyl) phenyl] -3-(2 -methyl -1., 2,3,4-tetrahydroisoquine-6-yl) -tetrahydroimidazole-2 -fluorene, id) 1- [4- [2- (isobutoxycarbonyl) ethyl] benzene Radical] -3-π, 2,3,4-tetrahydroisoquinoline-6-yl) -tetrahydrooxazole-2 -fluorene, i'e) b [4- (2-carboxyethyl) benzene Base] -3- (2,3,4,5 -tetrahydro-1Η-3 -benzobenzoazine-7-ridge) -tetrahydroimidazole-2 -pyrene, Consumer Cooperative of the Central Bureau of Standards, Ministry of Economic Affairs Print (f ') 1-[4-[2-(methoxycarbonyl) ethyl] phenyl] -3-(2, 3, 4,5 -tetrahydro-1 H- 3- ¾-monoazine Qiyuan-7-yl) -tetrahydroimidazole-2-copper, (§) 1- [4- [2- (isopropoxylophilic) ethyl] fluorenyl] -3- (2,3,4 , 5 -tetrahydro-1 Η-3-caged-nitrogen heptamidine-+7 -based) -tetrahydromibe-2-S -4-This paper is suitable for use again National Standards (CNS> M Specifications (210X297 mm) A8 B8 C8 D8 S84286 VI. Patent Application Scope (Please read the precautions on the back before filling this page) (Fly) 1- [4- (2-carboxyethyl ) Cagel] -3- (3-methyl-2,3,4,5-tetrahydro-ij-3 -benzobenzoazine-7-yl I-gg ^ gmm-2 -fluorene, (Π 4- [4- [2- (Postylethyl) phenyl] -5-methyl-2- (2,3,4,5-tetra'hydro-1H-3-benzo-azahepta-7 -Yl) -4fluorene-1,2,4-triazole-3, 3-fluorene, fluorene V- [trans-4-(2-carboxyethyl) cyclohexyl] -3-(2., 1.? 4, 5 -Tetrahydro-1H-3 -benzobenzoazine-7-yl) -tetrahydrozole-2-, (k) b [4- [2- (· methoxycarbonyl) ethyl] phenyl ] -3- (3-methyl- '2, 3,4, 5 -tetrafluorene-1 fluorene-3 -benzo-nitroazine fluorene ": ζ -yl) -tetrahydro_,' 0 _ 2 _ , ... '. U) 1-[4-[2-(ethoxycarbonyl) ethyl] .benzene ... yl. 1 -3, (3-methyl-2,3,4,5- Tetrahydro-1fluorene-3-benzodiazepam-7-7-yl) -tetrahydroimidal-2-copper, (11)) 1- [4- [2- (isopropoxy.mineral .. ) Ethyl] benzyl] -3- (3-methyl-, -2, 3,4, 5 -tetrahydro-1 fluorene-3 -benzo-azahepta-7 -yl -Tetrahydroimidazole-2 -fluorene, (η)]-[trans-4- (2-carboxyethyl) cyclohexyl] -3-U-methyl-2,3,4,5-tetrahydro-1 Η -3 -Benzodiazepine-7-yl) -tetraSoxazole-2-_, and its C-3 alkyl esters, manufactured by the Consumer Cooperatives of the Staff of the Central Standards Bureau of the Ministry of Economic Affairs (〇) 1- [反-4- [2- (isopropoxycarbonyl) ethyl] cyclohexyl] -3- (3-methyl-2,3,4,5-tetrahydro-1 {^-3-benzomonoazine圜 -7-yl) -tetrahydrooxazole-2-_ * (P) 1- [trans-4- [2- (ethoxycarbonyl) ethyl] cyclohexyl] -3- (3-methyl- 2,3,4,5-tetrahydro-] 1-3-benzodiazepine-7-yl) -tetrahydro This paper is sized to the Chinese National Standard (CNS) A4 (210 X 297 mm) ABCD S84286 6. Scope of patent application Hosial-2-嗣, (Please read the precautions on the back before filling this page) U ') 1- [trans-4- [2- (methoxycarbonyl) ethyl] cyclohexyl ] -3- (3-methyl-2,3,4,5-tetrahydro-1 [{-3-benzo-azahepta-7-yl) -tetrahydrofuran-2 -face, (r ) 1- [trans-4-[(carboxymethyl) · oxy] cyclohexyl] .- 3- (3-methyl- 2.3.4.5- tetrahydro-1H-3 -benzo-nitroazine-7- ) -Tetrahydrooxazole-2-_, U) 3- [trans-4- (2-carboxymethyl) Hexyl] -1- (3-methyl-2,3,4,5-tetrahydro-1H-3 -benzodiazepine-7-yl)-allantoin and (t) 1- [trans- 4- (2-carboxyethyl) cyclohexyl] -3- (3-ethyl-2,3, 4.5-tetrahydro-1.3-benzo-nitroazahepta-7-yl) -tetrahydrooxazole-2 -_, (U) 1-[trans-4-(2 -carboxyethyl) cyclohexyl] -3-(7 -ethyl-β, 7,8,9-tetrahydro-5H-da-coupling [2 , 3-d] -azahepta-2-yl) -tetrahydroimidazole-2-_ and tautomers and their salts. 4. The compound of formula (I) according to item 3 of the scope of patent application, which is (n) l-[trans- 4- (2-carboxyethyl) cyclohexyl] -3-U-methyl-2,3 , 4.5- Tetrahydro-1} {-3-Benzodiazepine-7-yl) -tetrahydroquinone-2-fluorene, its Ci-3 alkyl ester, printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs And its salts. 5. The compound of formula (I) according to item 4 of the scope of patent application, which is (η) 1- [trans-4- (2-carboxyethyl) cyclohexyl] -3- (3-methyl-2, 3, 4.5- Tetrahydro-11 ^ 3-Benzodiazepine-7-yl) -tetrahydrooxazole-2-fluorene-6-This paper size applies to China National Standard (CNS) A4 (210X297) (Centi) A8 884286? 8 D8 6. The scope of patent application, not its salts. 6. The compound of formula (I) according to item 3 of the patent application scope of radical stroke, which is (u) 1-[trans-4- (2-carboxyethyl) cycloamidine..meaning] -3di-XZ- Ethyl, 6,7,8,9-23 hydrogen-5 | {-daco [2,3-〇1] -azahepta-2-yl) -tetra,-...-hydrogen Luzol-2-copper, and its salts. 7. A cyclic derivative of formula (I) according to the scope of patent application of item No. 1 in which the salts are physiologically acceptable hydrazones formed with inorganic or organic acids or bases. 8.-A peony composition using M anti-cell agglutination or anti-coagulation, including a compound or root according to any one of claims 1 to 6 in the scope of patent application. Accepted salts, as appropriate, with 1 or more idler crossbones and / or diluents. ^ Jh. Emperor of any one of the scope of the patent application] [7], which is used to prepare a peony composition, which is suitable to combat or prevent the occurrence of smaller or larger cell aggregation or accompanying bundles Diseases of Intercellular Matrix Interaction (Please read the notes on the back before filling this page) Printed on the paper by the Consumers' Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs The paper size is applicable to the Chinese National Standard (CNS) Α4 (2Ι0 × 297 mm) S8428G Application Issue No. 83.02.17 Announcement of this class ~ 1 / 〇 «: 83101259 _ ^ each block is to be filled by this Office) Α4 -C4- Int.-Gr 384286 8 September 2004 amendment page) New ^ Patent The description of the invention invented the new name Ren Ming Zuo Chuang Chinese novel cyclic urea # 生物, and its use Hang Hang Ning and Hang coagulation Xu English first name country " HOVEL CYCLIC UREA DERIVATIVES AND THEIR USE IH INHIBITING CELL AiSGREGATION AND THROMBOSIS " Hagbabus, Tussen, Misler, Weissingbo, H. Gumou,, Pai Lin., Sk., Ha. Ensnalam, Klemmah, Fahfo, G., and Tom, LJ " a4 -5-ats No. 7. No. 1 Tiger i8! R Street 'No. 6' t: 1 5 7 Lane Tiger. Street Street Street grid, Lei 51 National grid Gegway cloth street Meiweiweiwei blue 24 sig 5. Red and blue Seoul Street, Poway, Bober City, Germany, Germany, Kai Kai m, Qu Boyuhai · Derry City, Ruili City, 'Junbo Qu, Quxu Ququ 7. 7. Ruirui City Ruirui 6 . Dubebodsenbobo 4. Mibibi Mikobibi 3 countries nations nations nations 2 dedede dedede i.l.2.a4.Ld6.7 Disguise · Customs printed name (name) of the Employees' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Nationality Dr. Carl Tom Co., Ltd. Germans invite S3 to live and live in. (Office) Representative name Birkenstock, Germany 65 Dover Street This paper uses Chinese National Standard (CNS) M specifications (210X297 mm). Line trouble 1 |: · Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs Scoop in 36 ml of ethoxylate. After stirring at 45 t for 2 hours, the mixture was cooled to -5 C and stirred for another 2 hours. The precipitate was filtered by suction and washed with cold acetonitrile. Yield: 2 · 6 g. (Theoretical value i 3 〇 X;), melting point: 2 1 3-2 1 5 »I 埴: 0. Β〇ί'silicone ; Diazomethane / methanol = 20 ·· 1: 1) The following compounds are similar to the decoration of Example 4: ':] > 1-('. 3- 茕 tributoxycarbonyl-2,3,4, 5-Cyclohydro-1 «-3-benzo-pyridine-7-yl) -3- [4-ί2-ίmethoxyfluorenyl) ethyl] cyl: -tetrahydro_ ran-2- _ ： 1 6 Β-1 6 7 * I ί Speech: 0. 7 7 (Nep; dichloromethane. / Ethyl acetate = 9: i) |, 2 > ί- [反-[4-[2- (Methoxycarbonyl) ethyl] cyclohexyl] -3- (3-trifluoroethyl-yl-2,3,4,5-tetrahydro-1 «-3-capped-nitrogen ±: 圜 -7- Base) -tetrahydrocycline 2 2-嗣 瑢 IA: 250-255tM. Decomposition), h value: 0.45 (silicon hydrazone; cyclohexane / ethyl acetate = 1: 1) (3) Bu [4- [反-2- (trioxycarbonyl) vinyl] phenyl] -3-ί3-trifluoroethyl_lane-2,3,4,5-tetrahydro-11 "!-3-benzo-nitroazine- 7-yl) -tetrahydroalyzol-2-_ 锫 point: 21β-22〇υ, R letter ·· 0.3 δ (silicon; cyclohexane / ethyl acetate = 1 ·. 1) 『4 ) 1- [trans-4- [2- (Cyclooxycarbonyl) ethyl 1cyclohexyl ] -3- (3-trioxethenyl-2.3,4.5-tetrahydro-14-3-cage and one nitrogen heptam-7-yl)-(Please read the precautions on the back before filling this page) i., 1T This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm)） .S3101259 patent application case A8-B8 Chinese ΦPlease amend the scope of patent too (March 86) C8 D8 Continue to ask members to indicate whether the original substantive internal reference will be changed after the revision of the 4V case. Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs. Patent production. I. Cyclic derivative of formula (I) X γ ω (Where: X is not slender, S, Y represents CH 2 C .H 2, (: H = C 、, CH 2 C 0 or C 0 C Η 2 group, or optionally K. methyl-substituted C Η = Ν or N = C Η group; R a represents A-Β group preferably Φ, X * A represents one of the following formula ΓΓν ^ Ν 14 (CH --------- Ti ---- / 'ί (Please read the precautions on the back before filling out this page) CH 2 CH 2 C 1 to 2 sessions of methine in the benzo portion of K-Nitrogen-1 This paper size applies to Chinese National Standard (CNS) A4 (210 X 297 mm)