Patent EA-004499-B1 (EA)
Title: Substituted heterocyclic compounds for treating of inflammatory processes
Inventor: CARTER JEFFERY F
IPC: A61K31/35
Filed: 1998-04-18
Abstract: 1. A compound of formula I' wherein X is selected from O, S, CR<C>R<B> and NR<A>; wherein R<A> is selected from the group, comprising hydrido, C1-C3-alkyl, phenyl-C1-C3-alkyl, (substituted phenyl)-C1-C3-alkyl where the phenyl ring is substituted with 1 to 3 substituents selected from C1-C6-alkyl, hydroxy, halo, haloalkyl, nitro, cyano, alkoxy and C1-C6-alkylamino, acyl and carboxy-C1-C6-alkyl; wherein each of R<B> and R<C> is independently selected from the group, comprising hydrido, C1-C3-alkyl, phenyl-C1-C3-alkyl, C1-C3-perfluoroalkyl, chloro, C1-C6-alkylthio, C1-C6-alkoxy, nitro, cyano and cyano-C1-C3-alkyl; wherein R is selected from carboxyl, aminocarbonyl, C1-C6-alkylsulfonylaminocarbonyl and C1-C6-alkoxycarbonyl; wherein R" is selected from the group, comprising hydrido, phenyl, thienyl and C2-C6-alkenyl; wherein R<1> is selected from the group, comprising hydrido, C1-C3-perfluoroalkyl, chloro, C1-C6-alkylthio, C1-C6-alkoxy, nitro, cyano and cyano-C1-C3-alkyl; wherein R<2> is one or more radicals independently selected from hydrido, halo, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, halo-C2-C6-alkynyl, (C6-C10-aryl)-C1-C3-alkyl, (C6-C10-aryl)-C2-C6-alkynyl, (C6-C10-aryl)-C2-C6-alkenyl, C1-C6-alkoxy, methylenedioxy, C1-C6-arylthio, C1-C6-alkylsulfinyl, (C6-C10-aryl)-oxygroup, (C6-C10-aryl)-thiogroup, (C6-C10-aryl)-sulfinyl, -O-(aromatic 5-6-membered heterocycle, containing 1 or 2 heteroatoms, selected independently from each other from N, O and S), C1-C6-alkoxy-C1-C6-alkyl, (C6-C10-aryl)-C1-C6-alkyloxy, (aromatic 5-6-membered heterocycle, containing 1 or 2 heteroatoms, selected independently from each other from N, O and S)-C1-C6-alkoxy, (C6-C10-aryl)-C1-C6-alkyloxy-C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-haloalkoxy, C1-C6-haloalkylthio, C1-C6-haloalkylsulfinyl, C1-C6-haloalkylsulfonyl, C1-C3-haloalkyl-C1-C3, C1-C6-hydroxyalyl, hydroxyimino-C1-C6-alkyl, C1-C6-alkylamino, (C6-C10-aryl)-amino, (C6-C10-aryl)-C1-C6-alkylamino, (aromatic 5-6-membered heterocycle, containing 1 or 2 heteroatoms, selected independently of each other from N, O and S)-amino, (aromatic 5-6-membered heterocycle, containing 1 or 2 heteroatoms, selected independently of each other from N, O and S)-C1-C6-alkylamino, nitro, cyano, amino, aminosulfonyl, C1-C6-alkylaminosulfonyl, (C6-C10-aryl)-aminosulfonyl, (aromatic 5-6-membered heterocycle, containing 1 or 2 heteroatoms, selected independently of each other from N, O and S)-aminosulfonyl, (C6-C10-aryl)-alkylaminosulfonyl, (aromatic 5-6-membered heterocycle, containing 1 or 2 heteroatoms, selected independently of each other from N, O and S)-C1-C6-alkylaminosulfonyl, (partially or entirely substituted with 5-6-membered heterocycle, containing 1 or 2 heteroatoms, selected independently of each other from N, O and S)-sulfonyl, C1-C6-alkylsulfonyl, (C6-C10-aryl)-C1-C6-alkylsulfonyl, optionally substituted with C6-C10-aryl, optionally substituted aromatic 5-6-membered heterocycle, containing 1 or 2 heteroatoms, selected independently of each other from N, O and S, (C6-C10-aryl)-C1-C6-alkylcarbonyl, (aromatic 5-6-membered heterocycle, containing 1 or 2 heteroatoms, selected independently of each other from N, O and S)-C1-C6-alkylcarbonyl, (aromatic 5-6-membered heterocycle, containing 1 or 2 heteroatoms, selected independently of each other from N, O and S)-carbonyl, (C6-C10-aryl)-carbonyl, aminocarbonyl, C1-C6-alkoxycarbonyl, formyl, C1-C6-haloalkyl and C1-C6-alkylcarbonyl; and and wherein the A ring atoms -A<1>, A<2>, A<3> and A<4> are independently selected from carbon and nitrogen with the proviso that at least two of A<1>, A<2>, A<3> and A<4> are carbon; or wherein R<2> together with ring a forms a radical selected from naphthyl, quinolyl, isoquinolyl, quinolizinyl, quinoxalinyl and dibenzofuryl; or an isomer or pharmaceutically acceptable salt thereon. 2. Compound of claim 1, in which X is selected from O, S, CR<C>R<B> and NR<A>; wherein R<A> is selected from the group, comprising hydrido, C1-C3-alkyl, phenyl-C1-C3-alkyl, (substituted phenyl)-C1-C3-alkyl where the phenyl ring is substituted with 1 to 3 substituents selected from C1-C6-alkyl, hydroxy, halo, haloalkyl, nitro, cyano, alkoxy and C1-C6-alkylamino, acyl and carboxy-C1-C6-alkyl; wherein each of R<B> and R<C> is independently selected from the group, comprising hydrido, C1-C3-alkyl, phenyl-C1-C3-alkyl, C1-C3-perfluoroalkyl, chloro, C1-C6-alkylthio, C1-C6-alkoxy, nitro, cyano and cyano-C1-C3-alkyl; wherein R is selected from carboxyl, aminocarbonyl, C1-C6-alkylsulfonylaminocarbonyl and C1-C6-alkoxycarbonyl; wherein R" is selected from the group, comprising hydrido, phenyl, thienyl and C2-C6-alkenyl; wherein R<1> is selected from the group, comprising hydrido, C1-C3-perfluoroalkyl, chloro, C1-C6-alkylthio, C1-C6-alkoxy, nitro, cyano and cyano-C1-C3-alkyl; wherein R<2> is one or more radicals independently selected from hydrido, halo, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, halo-C2-C6-alkynyl, (C6-C10-aryl)-C1-C3-alkyl, (C6-C10-aryl)-C2-C6-alkynyl, (C6-C10-aryl)-C2-C6-alkenyl, C1-C6-alkoxy, methylenedioxy, C1-C6-arylthio, C1-C6-alkylsulfinyl, (C6-C10-aryl)-oxygroup, (C6-C10-aryl)-thiogroup, (C6-C10-aryl)-sulfinyl, -O-(aromatic 5-6-membered heterocycle, containing 1 or 2 heteroatoms, selected independently from each other from N, O and S), C1-C6-alkoxy-C1-C6-alkyl, (C6-C10-aryl)-C1-C6-alkyloxy, (aromatic 5-6-membered heterocycle, containing 1 or 2 heteroatoms, selected independently from each other from N, O and S)-C1-C6-alkoxy, (C6-C10-aryl)-C1-C6-alkyloxy-C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-haloalkoxy, C1-C6-haloalkylthio, C1-C6-haloalkylsulfinyl, C1-C6-haloalkylsulfonyl, C1-C3-haloalkyl-C1-C3, C1-C6-hydroxyalyl, hydroxyimino-C1-C6-alkyl, C1-C6-alkylamino, (C6-C10-aryl)-amino, (C6-C10-aryl)-C1-C6-alkylamino, (aromatic 5-6-membered heterocycle, containing 1 or 2 heteroatoms, selected independently of each other from N, O and S)-amino, (aromatic 5-6-membered heterocycle, containing 1 or 2 heteroatoms, selected independently of each other from N, O and S)-C1-C6-alkylamino, nitro, cyano, amino, aminosulfonyl, C1-C6-alkylaminosulfonyl, (C6-C10-aryl)-aminosulfonyl, (aromatic 5-6-membered heterocycle, containing 1 or 2 heteroatoms, selected independently of each other from N, O and S)-aminosulfonyl, (C6-C10-aryl)-alkylaminosulfonyl, (aromatic 5-6-membered heterocycle, containing 1 or 2 heteroatoms, selected independently of each other from N, O and S)-C1-C6-alkylaminosulfonyl, (partially or entirely substituted with 5-6-membered heterocycle, containing 1 or 2 heteroatoms, selected independently of each other from N, O and S)-sulfonyl, C1-C6-alkylsulfonyl, (C6-C10-aryl)-C1-C6-alkylsulfonyl, optionally substituted with C6-C10-aryl, optionally substituted aromatic 5-6-membered heterocycle, containing 1 or 2 heteroatoms, selected independently of each other from N, O and S, (C6-C10-aryl)-C1-C6-alkylcarbonyl, (aromatic 5-6-membered heterocycle, containing 1 or 2 heteroatoms, selected independently of each other from N, O and S)-C1-C6-alkylcarbonyl, (aromatic 5-6-membered heterocycle, containing 1 or 2 heteroatoms, selected independently of each other from N, O and S)-carbonyl, (C6-C10-aryl)-carbonyl, aminocarbonyl, C1-C6-alkoxycarbonyl, formyl, C1-C6-haloalkyl and C1-C6-alkylcarbonyl; and and wherein the A ring atoms -A<1>, A<2>, A<3> and A<4> are independently selected from carbon and nitrogen with the proviso that at least two of A<1>, A<2>, A<3> and A<4> are carbon; or wherein R<2> together with ring a forms a radical selected from naphthyl, quinolyl; or an isomer or pharmaceutically acceptable salt thereon. 3. Compound of claim 2, in which X is selected from O, S, CR<C>R<B> and NR<A>; wherein R<A> is selected from the group, comprising hydrido, C1-C3-alkyl, phenyl-C1-C3-alkyl, (substituted phenyl)-C1-C3-alkyl where the phenyl ring is substituted with 1 to 3 substituents selected from C1-C6-alkyl, hydroxy, halo, haloalkyl, nitro, cyano, alkoxy and C1-C6-alkylamino, acyl and carboxy-C1-C6-alkyl; wherein R is selected from carboxyl; wherein R" is selected from the group, comprising hydrido, and C2-C6-alkenyl; wherein R<1> is C1-C3-perfluoroalkyl; wherein R<2> is one or more radicals independently selected from hydrido, halo, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, halo-C2-C6-alkynyl, phenyl-C1-C6-alkyl, phenyl-C1-C6-alkynyl, phenyl-C1-C6-alkenyl, C1-C3-alkoxy, methylenedioxy, C1-C3-alkoxy-C1-C3-alkyl, C1-C3-alkylthio, C1-C3-alkylsulfinyl, phenyloxy, phenylthio, phenylsulfinyl, C1-C3-haloalkyl-C1-C3-hydroxyalkyl, phenyl-C1-C3-alkyloxy-C1-C3-alkyl, C1-C3-haloalkyl, C1-C3-haloalkoxy, C1-C3-haloalkylthio, C1-C3-hydroxyalkyl, hydroxyimino-C1-C3-alkyl, C1-C3-alkylamino, nitro, cyano, amino, aminosulfonyl, N-alkylaminosulfonyl, N-arylaminosulfonyl, N-heteroarylaminosulfonyl, N-(phenyl-C1-C6-alkyl)aminosulfonyl, N-(heteroaryl-C1-C6-alkyl)aminosulfonyl, phenyl-C1-C3-alkylsulfonyl, 5- to 8-membered heterocyclylsulfonyl, C1-C6-alkylsulfonyl, optionally substituted, phenyl, optionally substituted 5- to 9-membered heteroaryl, phenyl-C1-C6-alkylcarbonyl, phenylcarbonyl, 4-chlorophenylcarbonyl, 4-hydroxyphenylcarbonyl, 4-trifluoromethylphenylcarbonyl, 4-methexyphenylcarbonyl, aminocarbonyl, formyl, and C1-C6-alkylcarbonyl; and wherein the A ring atoms -A<1>, A<2>, A<3> and A<4> are independently selected from carbon and nitrogen with the proviso that at least two of A<1>, A<2>, A<3> and A<4> are carbon; or wherein R<2> together with ring a forms a radical selected from naphthyl, benzofurylphenyl or quinolyl; or an isomer or pharmaceutically acceptable salt thereon. 4. Compound according to claim 3, in which X is selected from the group, consisting of O, S, CR<C>R<B> and NR<A> wherein R<A> is selected from the group, comprising hydrido, methyl, ethyl, 4-trifluoromethyl benzyl, (4-chloromethyl)benzyl, (4-methoxy benzyl, and (4-cyano)benzyl, (4-nitro)benzyl; wherein R is carboxyl; wherein R" is selected from hydrido and ethenyl; wherein R<1> is selected fr