RU2002110102A

RU2002110102A - Bicyclic derivatives of imidazo-3-ylamine

Info

Publication number: RU2002110102A
Application number: RU2002110102/04A
Authority: RU
Inventors: Маттиас ГЕРЛАХ; Коринна МАУЛЬ
Original assignee: Грюненталь Гмбх
Priority date: 1999-10-08
Filing date: 2000-09-18
Publication date: 2003-12-20

Claims

1. Bicyclic imidazo-3-ylamines of the general formula I

in which X and Y represent CH or N, provided that X and Y do not simultaneously denote N,

R ¹ is tert-butyl, (CH ₂ ) _n CN, where n is 4, 5 or 6, optionally substituted phenyl, C ₄ -C ₈ cycloalkyl, CH ₂ CH ₂ R (R is 4-morpholine), 1,1 , 3,3-tetramethylbutyl or CH ₂ R ^a , where R ^a represents hydrogen, OH, C ₁ -C ₈ alkyl (branched or unbranched), optionally substituted phenyl, CO (OR ') (where R' is unbranched C ₁ -C ₄ alkyl or branched C ₁ -C ₅ alkyl), PO (OR ') ₂ (where R' is straight-chain C ₁ -C ₄ alkyl or branched C ₁ -C ₅ alkyl) or Si (R ^X R ^Y R ^Z ) (where R ^X , R ^Y and R ^Z each independently from each other means C ₁ -C ₄ alkyl (times branched or unbranched), C ₄ -C ₈ cycloalkyl or phenyl),

R ² is hydrogen, COR ^b , where R ^b is C ₁ -C ₄ alkyl (branched or unbranched) or C ₃ -C ₈ cycloalkyl, CH ₂ CH ₂ CO (OR ^c ), where R ^c is C ₁ - C ₄ alkyl (branched or unbranched), adamantyl, optionally substituted phenyl, optionally substituted 1-naphthyl or 2-naphthyl or respectively optionally substituted 2-pyridyl, 3-pyridyl, 4-pyridyl, thiazolyl or furoyl, CH ₂ phenyl, CH ₂ CH ₂ R ^d , where R ^d is optionally substituted phenyl, or CONHR ^e , where R ^e is C ₁ -C ₈ alkyl (whether branched more unbranched), C ₃ -C ₈ cycloalkyl or optionally substituted phenyl,

R ³ is methyl, ethyl, tert-butyl, C ₃ -C ₈ cycloalkyl, phenyl, optionally monosubstituted at position 3, 5 or 6, or optionally multisubstituted at position 4 and additionally at position 2 and / or 3 and / or 5 and / or 6, phenoxy, optionally substituted naphthyl, optionally substituted pyrrole, optionally substituted pyridyl, optionally substituted furan, optionally substituted thiophene, optionally substituted anthracene, optionally substituted phenanthrene or optionally substituted quinoline, with the proviso that R ³ does not denote n-pro yl, cyclohexyl, unsubstituted phenyl or monosubstituted in position 3 of group a carboxylic acid amide phenyl if R ¹ denotes mpem-butkp, n-propyl, n-butyl, 1,1,3,3-tetramethylbutyl, cyclohexyl, CH ₂ CH ₂ R (where R is 4-morpholine), a monosubstituted phenyl, 2,6-dimethylphenyl or benzyl and at the same time R ² is hydrogen or —CO (methyl, and that R ^{2 is} not hydrogen if at the same time R ¹ is benzyl and R ³ is methyl or simultaneously R ¹ is CH ₂ C (O) -t-butyl, and R ³ is unsubstituted phenyl, in the form of bases or in a pharmaceutically acceptable manner My salts.

2. The bicyclic imidazo-3-ylamines according to claim 1, characterized in that R ² is hydrogen,

R ^{1 is} selected from the group consisting of (CH ₂ ) _n CN, where n is 4, 5 or 6, cyclohexyl, CH ₂ CO (methyl), 2,6-dimethylphenyl, 1,1,3,3-tetramethylbutyl, tert- butyl or n-butyl, and

R ^{3 is} selected from the group consisting of 2-pyridyl, 3-pyridyl, 2-furanyl, 2-pyrroyl, methyl, tert-butyl, 3-hydroxyphenyl, 3,4-dimethoxyphenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl , 2-methoxyphenyl, 2,3-dimethoxyphenyl, 3-bromophenyl, 4-bromo-2-fluorophenyl, 5-bromo-2-fluorophenyl, 3-bromo-4-fluorophenyl, 3-chlorophenyl, 3,4-dichlorophenyl, 3 -fluorophenyl, 3-methylphenyl, 3-phenoxyphenyl, 3- (4-chlorophenoxy) phenyl, 2-chloro-4-fluorophenyl, 2-chloro-6-fluorophenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2- bromophenyl, 2-fluorophenyl or 2- (trifluoromethyl) phenyl.

3. The bicyclic imidazo-3-ylamines according to claim 1 or 2, characterized in that they are the following compounds: (6-isocyanohexyl) - (2-pyridin-2-imidazo [1,2-a] pyridin-3- il) amine, (2-furan-2-imidazo [1,2-a] pyridin-3-yl) - (6-isocyanohexyl) amine, (2-cyclohexylimidazo [1,2-a] pyrazin-3-yl) - (6-Isocyanohexyl) amine, (2,6-dimethylphenyl) - (2-furan-2-imidazo [1,2-a] pyridin-3-yl) amine, methyl ester (2-furan-2-imidazo [ 1,2-a] pyrazin-3-ylamino) acetic acid, (2-cyclohexylimidazo [1,2-a] pyrimidin-3-ylamino) acetic acid methyl ester, (2-methylimidazo [1,2-a] methyl ester pyrazin-3- amylamino) acetic acid, (2-pyridin-4-imidazo [1,2-a] pyrazin-3-yl) - (1,1,3,3-tetramethylbutyl) amine, (2-methylimidazo [1,2-a ] pyrazin-3-yl) - (1,1,3,3-tetramethylbutyl) amine, 3- (3-tert-butylaminoimidazo [1,2-a] pyridin-2-yl) phenol, butyl [2- (2 , 3-Dichlorophenyl) imidazo [1,2-a] pyrazin-3-yl] amine, diethyl ether [(2-phenylimidazo [1,2-a] pyridin-3-ylamino) methyl] phosphonic acid, tert-butyl ( 2-tert-butylimidazo [1,2-a] pyridin-3-yl) amine, butyl (2-o-tolylimidazo [1,2-a] pyrimidin-3-yl) amine, (2,6-dimethylphenyl) - [2- (2-methoxyphenyl) imidazo [1,2-a] pyrazin-3-yl] amine, butyl (2-o-tolylimidazo [1,2-a] pyrimidin-3-yl) amine, tert-but yl (2-pyridin-3-ylamidazo [1,2-a] pyrimidin-3-yl) amine, tert-butyl (2-methylimidazo [1,2-a] pyridin-3-yl) amine, [2- ( 1H-pyrrol-2-yl) imidazo [1,2-a] pyrimidin-3-yl)] - (1,1,3,3-tetramethylbutyl) amine, cyclohexyl (2-furan-2-yl imidazo [1,2 -a] pyridin-3-yl) amine, tert-butyl (2-pyridin-3-yl imidazo [1,2-a] pyridin-3-yl) amine, tert-butyl (2-pyridin-2-yl imidazo [1 , 2-a] pyridin-3-yl) amine, tert-butyl (2-thiophen-2-imidazo [1,2-a] pyridin-3-yl) amine, cyclohexyl (2-methylimidazo [1,2-a ] pyridin-3-yl) amine, N-cyclohexyl-N- [2- (5-methylfuran-2-yl) imidazo [1,2-a] pyridin-3-yl] acetamide, tert-butyl [2- ( 5-methylsulfanylthiophen-2-yl) imidazo [1,2-a] pyr imidin-3-yl] amine, [2- (3-bromothiophen-2-yl) imidazo [1,2-a] pyridin-3-yl] cyclohexylamine, 2-methoxy-4- [3- (1,1, 3,3-tetramethylbutylamino) imidazo [1,2-a] pyrimidin-2-yl] phenyl ester of acetic acid, [2- (2-chloro-4-fluorophenyl) imidazo [1,2-a] pyrimidin-3-yl ] - (1,1,3,3-tetramethylbutyl) amine, (2-anthracene-9-imidazo [1,2-a] pyrazin-3-yl) tert-butylamine, tert-butyl (2-naphthalen-1- imidazo [1,2-a] pyridin-3-yl) amine, N-cyclohexyl-N- [2- (4,5-dimethylfuran-2-yl) imidazo [1,2-a] pyrimidin-3-yl] acetamide and (1,1,3,3-tetramethylbutyl) - [2- (3,4,5-trimethoxyphenyl) imidazo [1,2-a] pyridin-3-yl] amine.

4. A medicine containing in its composition as an active substance at least one bicyclic imidazo-3-ylamine of the general formula I according to claim 1, in which R ¹ , R ² , R ³ , X and Y have the meanings indicated in claim 1, in the form of a base or a pharmaceutically acceptable salt.

5. The drug according to claim 4, characterized in that it contains at least one bicyclic imidazo-3-ylamine selected from the group consisting of (6-isocyanohexyl) - (2-pyridin-2 -ilimidazo [1,2-a] pyridin-3-yl) amine, (2-furan-2-yl imidazo [1,2-a] pyridin-3-yl) - (6-isocyanohexyl) amine, (2-cyclohexylimidazo [1,2-a] pyrazin-3-yl) - (6-isocyanohexyl) amine, (2,6-dimethylphenyl) - (2-furan-2-imidazo [1,2-a] pyridin-3-yl) amine, (2-furan-2-imidazo [1,2-a] pyrazin-3-ylamino) acetic acid methyl ester, (2-cyclohexylimidazo [ 1,2-a] pyrimidin-3-ylamino) acetic acid, methyl (2-methylimidazo [1,2-a] pyrazin-3-ylamino) acetic acid, (2-pyridin-4-ylamidazo [1,2- a] pyrazin-3-yl) - (1,1,3,3-tetramethylbutyl) amine, (2-methylimidazo [1,2-a] pyrazin-3-yl) - (1,1,3,3-tetramethylbutyl ) amine, 3- (3-tert-butylaminoimidazo [1,2-a] pyridin-2-yl) phenol, butyl [2- (2,3-dichlorophenyl) imidazo [1,2-a] pyrazin-3-yl ] amine, diethyl ether [(2-phenylimidazo [1,2-a] pyridin-3-ylamino) methyl] phosphonic acid, tert-butyl (2-tert-butylimidazo [1,2-a] pyridin-3-yl) amine, butyl (2-o-tolylimidazo [1,2-a] pyrimidin-3-yl) amine, (2,6-dimethylphenyl) - [2- (2-methoxypheni k) imidazo [1,2-a] pyrazin-3-yl] amine, butyl (2-o-tolylimidazo [1,2-a] pyrimidin-3-yl) amine, tert-butyl (2-pyridin-3- imidazo [1,2-a] pyrimidin-3-yl) amine, tert-butyl (2-methylimidazo [1,2-a] pyridin-3-yl) amine, [2- (1H-pyrrol-2-yl) imidazo [1,2-a] pyrimidin-3-yl)] - (1,1,3,3-tetramethylbutyl) amine, cyclohexyl (2-furan-2-imidazo [1,2-a] pyridin-3-yl ) amine, tert-butyl (2-pyridin-3-ylamidazo [1,2-a] pyridin-3-yl) amine, tert-butyl (2-pyridin-2-ylamidazo [1,2-a] pyridin-3 -yl) amine, tert-butyl (2-thiophen-2-imidazo [1,2-a] pyridin-3-yl) amine, cyclohexyl (2-methylimidazo [1,2-a] pyridin-3-yl) amine , N-cyclohexyl-N- [2- (5-methylfuran-2-yl) imide azo [l, 2-a] pyridin-3-yl] acetamide, tert-butyl [2- (5-methylsulfanylthiophen-2-yl) -imidazo [1,2-a] pyrimidin-3-yl] amine, [2 - (3-bromothiophen-2-yl) imidazo [1,2-a] pyridin-3-yl] cyclohexylamine, 2-methoxy-4- [3- (1,1,3,3-tetramethylbutylamino) imidazo [1, 2-a] pyrimidin-2-yl] phenyl ester of acetic acid, [2- (2-chloro-4-fluorophenyl) imidazo [1,2-a] pyrimidin-3-yl] - (1,1,3,3 -tetramethylbutyl) amine, (2-anthracene-9-imidazo [1,2-a] pyrazin-3-yl) tert-butylamine, tert-butyl (2-naphthalen-1-imidazo [1,2-a] pyridine- 3-yl) amine,

N-cyclohexyl-N- [2- (4,5-dimethylfuran-2-yl) imidazo [1,2-a] pyrimidin-3-yl] acetamide and (1,1,3,3-tetramethylbutyl) - [2 - (3,4,5-trimethoxyphenyl) imidazo [1,2-a] pyridin-3-yl] amine, or one of the pharmaceutically acceptable salts of these compounds.

6. The use of at least one bicyclic imidazo-3-ylamine according to claims 1, 2 or 3 in conjunction with one or more auxiliary substances to obtain the corresponding medicinal product intended for the fight against pain.

7. A method of producing bicyclic imidazo-3-ylamines according to claims 1, 2 or 3 by a three-way reaction using amidine, aldehyde and isonitrile, characterized in that the synthesis of these compounds is carried out in dichloromethane as a solvent in the presence of perchloric acid, with the starting the compounds are added in the following sequence: first amidine, then aldehyde and finally isonitrile, and the products obtained are then, under certain conditions, reacted with the compound R ² Hal or the isocyanate R ^e NCO.