Patent EA-004038-B1 (EA)
Title: Piperazine derivatives and their use as anti-inflammatory agents
Inventor: BAUMAN JOHN G
IPC: C07D403/06
Filed: 1998-06-11
Abstract: 1. A compound of the following formula (Ia): wherein: R<1A> is one or more substituents independently selected from the group consisting of oxo, halo, (C1-C8)alkyl, (C3-C10)cycloalkyl, (C3-C10)cycloalkyl(C1-C8)alkyl, (C3-C10)cycloalkylamino (C1-C8)alkyl, ((C3-C10)cycloalkyl(C1-C8)alkyl)amino(C1-C8)alkyl, halo(C1-C8)alkyl, (C2-C8) alkenyl, (C2-C8)alkynyl, optionally substituted phenyl or naphthyl, (optionally substituted phenyl or naphthyl)(C1-C8)alkyl, (optionally substituted phenyl or naphthyl)(C2-C8)alkenyl, formyl, formyl(C1-C8)alkyl, hydroxy(C1-C8)alkyl, hydroxy(C2-C8)alkenyl, hydroxy(C2-C8) alkynyl, (hydroxy)(optionally substituted phenyl or naphthyl)(C1-C8)alkyl, (hydroxy) (C3-C10) cycloalkyl(C1-C8)alkyl, mercapto(C1-C8)alkyl, cyano(C1-C8)alkyl, halo(C1-C8) alkylcarbonylamino(C1-C8)alkyl, ((C1-C8)alkoxy)(optionally substituted phenyl or naphthyl)(C1-C8)alkyl, (C1-C8) alkoxy(C1-C8)alkyl, (optionally substituted phenyl or naphthyl)oxy(C1-C8)alkyl, (optionally substituted phenyl or naphthyl)(C1-8) alkoxy (C1-C8) alkyl, (C1-C8)alkylthio(C1-C8)alkyl, (C1-C8)alkylsulfinyl(C1-C8)alkyl, (C1-C8) alkylsulfonyl(C1-C8)alkyl, hydroxy(C1-C8)alkylthio(C1-C8)alkyl, amino(C1-C8)alkyl, mono(C1-C8) alkylamino(C1-C8)alkyl, di(C1-C8)alkylamino(C1-C8)alkyl, mono(optionally substituted phenyl or naphthyl) amino(C1-C8)alkyl, mono(optionally substituted phenyl or naphthyl)(C1-C8)alkylamino(C1-C8)alkyl, (C1-C8) alkylcarbonylamino(C1-C8)alkyl, ((C1-C8) alkylcarbonyl)((C1-C8)alkyl)amino(C1-C8)alkyl, azido(C1-C8)alkyl, ureido(C1-C8)alkyl, mono(C1-C8)alkylureido(C1-C8)alkyl, di(C1-C8) alkylureido(C1-C8)alkyl, ((C1-C8) alkoxycarbonyl(C1-C8)alkyl)ureido(C1-C8)alkyl, (C1-C8)alkoxycarbonylamino(C1-C8)alkyl, hydroxy (C1-C8)alkylamino(C1-C8)alkyl, (optionally substituted phenyl or naphthyl)oxy(C1-C8) alkylcarbonyloxy(C1-C8)alkyl, (C1-C8)alkoxy(C1-C8) alkylcarbonyloxy (C1-C8)alkyl, (optionally substituted phenyl or naphthyl)(C1-C8)alkoxy(C1-C8) alkylcarbonyloxy(C1-C8) alkyl, (C1-C8)alkylcarbonyl, (C1-C8)alkylcarbonyl(C1-C8)alkyl; carboxy, (C1-C8) alkoxycarbonyl, (optionally substituted phenyl or naphthyl)(C1-C8) alkoxycarbonyl, (optionally substituted phenyl or naphthyl)(C1-C8)alkylcarbonyl, aminocarbonyl, mono(C1-C8) alkylaminocarbonyl, di(C1-C8)alkylaminocarbonyl, mono(optionally substituted phenyl or naphthyl)aminocarbonyl, mono(optionally substituted phenyl or naphthyl) (C1-C8) alkylaminocarbonyl, carboxy(C1-C8)alkyl, (C1-C8) alkoxycarbonyl (C1-C8)alkyl, (optionally substituted phenyl or naphthyl)(C1-8) alkoxycarbonyl(C1-C8)alkyl, aminocarbonyl (C1-C8) alkyl, mono(C1-C8) alkylaminocarbonyl(C1-C8)alkyl, di(C1-C8) alkylaminocarbonyl(C1-C8) alkyl, mono(optionally substituted phenyl or naphthyl) aminocarbonyl (C1-C8)alkyl, mono (optionally substituted phenyl or naphthyl)(C1-C8) alkylaminocarbonyl(C1-C8)alkyl, (optionally substituted phenyl or naphthyl) sulfonyl, 3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and (3-15) membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur)(C1-C8)alkyl; R<2> is one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, (C1-C8)alkyl, mercapto, mercapto(C1-C8)alkyl, (C1-C8) alkylthio, (C1-C8)alkylsulfinyl, (C1-C8)alkylsulfonyl, (C1-C8)alkylthio(C1-C8)alkyl, (C1-C8) alkylsulfinyl(C1-C8)alkyl, (C1-C8)alkylsulfonyl(C1-C8)alkyl, (C1-C8)alkoxy, (optionally substituted phenyl or naphthyl) oxy, halo(C1-C8)alkyl, formyl, formyl(C1-C8)alkyl, nitro, nitroso, cyano, (optionally substituted phenyl or naphthyl)(C1-C8)alkoxy, halo(C1-C8)alkoxy, (C3-C10) cycloalkyl, (C3-C10)cycloalkyl(C1-C8)alkyl, (hydroxy)(C3-C10)cycloalkyl(C1-C8)alkyl, (C3-C10) cycloalkylamino, (C3-C10) cycloalkylamino(C1-C8)alkyl, ((C3-C10) cycloalkyl (C1-C8) alkyl)amino, ((C3-10)cycloalkyl(C1-C8)alkyl)amino(C1-C8)alkyl, cyano(C1-C8)alkyl, (C2-C8) alkenyl, (C2-C8)alkynyl, optionally substituted phenyl or naphthyl, (optionally substituted phenyl or naphthyl)(C1-C8)alkyl, (optionally substituted phenyl or naphthyl)(C2-C8)alkenyl, hydroxy(C1-C8) alkyl, (hydroxy)(optionally substituted phenyl or naphthyl)(C1-C8)alkyl, hydroxy(C1-C8) alkylthio(C1-C8)alkyl, hydroxy(C2-C8)alkenyl, hydroxy(C2-C8)alkynyl, (C1-C8)alkoxy(C1-C8) alkyl, ((C1-C8)alkoxy) (optionally substituted phenyl or naphthyl)(C1-C8)alkyl, (optionally substituted phenyl or naphthyl)oxy(C1-C8)alkyl, (optionally substituted phenyl or naphthyl) (C1-C8) alkoxy(C1-C8)alkyl, amino, mono(C1-C8) alkylamino, di(C1-C8)alkylamino, mono(optionally substituted phenyl or naphthyl)amino, mono(optionally substituted phenyl or naphthyl)(C1-C8) alkylamino, amino(C1-C8)alkyl, mono(C1-C8)alkylamino(C1-C8)alkyl, di(C1-C8)alkylamino(C1-C8) alkyl, hydroxy(C1-C8) alkylamino(C1-C8)alkyl, mono(optionally substituted phenyl or naphthyl)amino(C1-C8)alkyl, mono(optionally substituted phenyl or naphthyl)(C1-C8) alkylamino(C1-C8)alkyl, (C1-C8) alkylcarbonylamino, ((C1-C8) alkylcarbonyl)((C1-C8) alkyl)amino, (C1-C8) alkylcarbonylamino (C1-C8)alkyl, ((C1-C8) alkylcarbonyl)((C1-C8) alkyl)amino(C1-C8)alkyl, (C1-C8) alkoxycarbonylamino, ((C1-C8) alkoxycarbonyl)((C1-C8) alkyl)amino, (C1-C8) alkoxycarbonylamino(C1-C8)alkyl, ((C1-C8) alkoxycarbonyl)((C1-C8) alkyl)amino(C1-C8)alkyl, carboxy, (C1-C8)alkoxycarbonyl, (optionally substituted phenyl or naphthyl)(C1-C8) alkoxycarbonyl, (C1-C8)alkylcarbonyl, (C1-C8) alkylcarbonyl(C1-C8)alkyl, (optionally substituted phenyl or naphthyl)carbonyl, (optionally substituted phenyl or naphthyl)carbonyl(C1-C8) alkyl, (optionally substituted phenyl or naphthyl)(C1-C8)alkylcarbonyl, (optionally substituted phenyl or naphthyl)(C1-C8) alkylcarbonyl(C1-C8)alkyl, carboxy(C1-C8) alkyl, (C1-C8) alkoxycarbonyl(C1-C8)alkyl, (optionally substituted phenyl or naphthyl)(C1-C8) alkoxycarbonyl(C1-C8)alkyl, (C1-C8) alkoxy(C1-C8)alkylcarbonyloxy(C1-C8)alkyl, aminocarbonyl, mono(C1-C8)alkylaminocarbonyl, di(C1-C8)alkylaminocarbonyl, mono (optionally substituted phenyl or naphthyl)aminocarbonyl, mono(optionally substituted phenyl or naphthyl)(C1-C8) alkylaminocarbonyl, aminocarbonyl(C1-C8) alkyl, mono(C1-C8) alkylaminocarbonyl(C1-C8) alkyl, di(C1-C8) alkylaminocarbonyl(C1-C8) alkyl, mono(optionally substituted phenyl or naphthyl)aminocarbonyl(C1-C8)alkyl, mono(optionally substituted phenyl or naphthyl)(C1-C8) alkylaminocarbonyl(C1-C8)alkyl, amidino, guanidino, ureido, mono(C1-C8) alkylureido, di(C1-C8) alkylureido, ureido(C1-C8)alkyl, mono(C1-C8)alkylureido (C1-C8) alkyl, di(C1-C8) alkylureido(C1-C8)alkyl, 3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and (3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur)(C1-C8) alkyl; R3 is a carbocyclic ring system substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, (C1-C8)alkyl, mercapto, mercapto (C1-C8)alkyl, (C1-C8)alkylthio, (C1-C8)alkylsulfinyl, (C1-C8)alkylsulfonyl, (optionally substituted phenyl or naphthyl)sulfonyl, (C1-C8)alkylthio(C1-C8)alkyl, (C1-C8) alkylsulfinyl(C1-C8)alkyl, (C1-C8) alkylsulfonyl(C1-C8)alkyl, (C1-C8)alkoxy, hydroxy(C1-C8) alkoxy, (optionally substituted phenyl or naphthyl) oxy, halo(C1-C8)alkyl, formyl, formyl (C1-C8) alkyl, nitro, nitroso, cyano, (optionally substituted phenyl or naphthyl) (C1-C8)alkoxy, halo(C1-C8)alkoxy, amino(C1-C8) alkoxy, (C3-C10)cycloalkyl, (C3-C10) cycloalkyl(C1-C8) alkyl, (hydroxy) (C3-C10)cycloalkyl(C1-C8) alkyl, (C3-C10) cycloalkylamino, (C3-C10) cycloalkylamino(C1-C8)alkyl, cyano(C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, optionally substituted phenyl or naphthyl, (optionally substituted phenyl or naphthyl)(C1-C8)alkyl, (optionally substituted phenyl or naphthyl) (C2-C8)alkenyl, hydroxy(C1-C8)alkyl, (hydroxy) (optionally substituted phenyl or naphthyl)(C1-C8)alkyl, (mono(C1-C8)alkylamino)(optionally substituted phenyl or naphthyl)(C1-C8)alkyl, (hydroxy(C1-C8) alkyl)thio(C1-C8)alkyl, hydroxy (C2-C8)alkenyl, hydroxy(C2-C8)alkynyl, (C1-C8)alkoxy(C1-C8) alkyl, ((C1-C8)alkoxy) (optionally substituted phenyl or naphthyl)(C1-C8)alkyl, (optionally substituted phenyl or naphthyl)oxy(C1-C8)alkyl, (optionally substituted phenyl or naphthyl)(C1-C8) alkoxy(C1-C8) alkyl, amino, mono(C1-C8)alkylamino, di(C1-C8)alkylamino, mono(optionally substituted phenyl or naphthyl)amino, mono(optionally substituted phenyl or naphthyl)(C1-C8) alkylamino, amino(C1-C8) alkylamino, (3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur)amino, ((C3-C10)cycloalkyl(C1-C8) alkyl) amino, alkylcarbonylamino, (C1-C8) alkoxycarbonylamino, (C2-C8) alkenylcarbonylamino, (C3-C10)cycloalkylcarbonylamino, (optionally substituted phenyl or naphthyl) carbonylamino, (3-15 membered heterocyclyl consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur)carbonylamino, halo(C1-C8) alkylcarbonylamino, (C1-C8) alkoxy(C1-C8) alkylcarbonylamino, (C1-C8) alkoxycarbonyl(C1-C8) alkylcarbonylamino, ((C1-C8) alkylcarbonyl)((C1-C8)alkyl)amino, ((C1-C8) alkoxycarbonyl)((C1-C8)alkyl)amino, (C1-C8) alkylsulfonylamino, amino(C1-C8)alkyl, mono(C1-C8)alkylamino(C1-C8)alkyl, di(C1-C8) alkylamino(C1-C8)alkyl, hydroxy(C1-C8) alkylamino(C1-C8)alkyl, mono(optionally substituted phenyl or naphthyl)amino(C1-C8)alkyl, mono(optionally substituted phenyl or naphthyl)(C1-C8) alkylamino(C1-C8)alkyl, (C1-C8)alkylcarbonylamino(C1-C8)alkyl, (optionally substituted phenyl or naphthyl)carbonylamino(C1-C8)alkyl, ((C1-C8)alkylcarbonyl) ((C1-C8) alkyl)amino(C1-C8) alkyl, ((C3-C10)cycloalkyl(C1-C8)alkyl)am