发明名称 Substituted fused imidazole derivatives, pharmaceutical compositions, and methods of use thereof
摘要 Substituted fused imidazole derivatives, methods of their preparation, pharmaceutical compositions comprising a substituted fused imidazole derivative, and methods of use in treating inflammation are provided. The substituted fused imidazole derivatives may control the activity or the amount or both the activity and the amount of heme-oxygenase.
申请公布号 US8759535(B2) 申请公布日期 2014.06.24
申请号 US201113028406 申请日期 2011.02.16
申请人 High Point Pharmaceuticals, LLC 发明人 Mjalli Adnan M. M.;Polisetti Dharma Rao;Kassis Jareer Nabeel;Kostura Matthew J.;Guzel Mustafa;Attucks Otis Clinton;Andrews Robert Carl;Victory Samuel;Gupta Suparna
分类号 C07D417/12;C07D235/30;C07D513/04;A61K31/437;A61K31/428;A61K31/4188;A61K31/4168 主分类号 C07D417/12
代理机构 代理人 Rollins Samuel B.
主权项 1. A compound of Formula (I), or a pharmaceutically acceptable salt thereof,wherein one of X1, X2, X3, and X4 is  and the remaining members of X1, X2, X3, and X4 are independently N or G is hydrogen, —C1-8 alkyl, —C3-10 cycloalkyl, —C1-6 alkylene-C3-10 cycloaklyl, heterocyclyl, —C1-6 alkylene-C3-10 heterocyclyl, phenyl, heteroaryl, or NRh Rk, where the alkyl, alkylene, cycloalkyl, heterocyclyl, phenyl, and heteroaryl groups are optionally substituted one or more times with substituents independently selected from Rc; L is —CH2—C(O)N(R6)—, —C(O)N(R6)—, —C(O)—O—, —SO2—, —C(O)—, heteroarylene optionally substituted one or more times with substituents independently selected from Rx, or heterocyclylene optionally substituted one or more times with substituents independently selected from Rx; or the group -L-G is -cyano; R1 is hydrogen, Ra, phenyl, or heteroaryl, where the phenyl and heteroaryl groups are optionally substituted one or more times with substituents independently selected from Rx; R2 is Rb; R3 is hydrogen, —C1-6 alkyl, or —C1-6 alkylene-C3-10 cycloaklyl, where the alkyl, alkylene, and cycloalkyl groups are optionally substituted one or more times with substituents independently selected from Rz; R4 is —C1-6 alkyl or —C1-6 alkylene-C3-10 cycloaklyl, where the alkyl, alkylene, and cycloalkyl groups are optionally substituted one or more times with substituents independently selected from Ry; R6 is hydrogen, —C1-6 alkyl, —C1-6 alkylene-C3-10 cycloaklyl, where the alkyl, alkylene, and cycloalkyl groups are optionally substituted one or more times with substituents independently selected from Rx; Ra is a) -halogen,b) —C1-6 alkyl,c) —C3-10 cycloalkyl,d) -heterocyclyl,e) -cyano,f) —CF3,g) —OCF3,h) —O—Rd,i) —S(O)w—Rd,j) —S(O)2O—Rd,k) —NRdRe,l) —C(O)—Rd,m) —C(O)—O—Rd,n) —OC(O)—Rd,o) —C(O)NRd Re,p) —C(O)-heterocyclyl,q) —NRd C(O)Re,r) —OC(O)NRd Re,s) —NRd C(O)ORd, ort) —NRd C(O)NRd Re,where the alkyl, cycloalkyl, and heterocyclyl groups are optionally substituted one or more times with substituents independently selected from Ry; Rb is a) -halogen,b) —C1-6 alkyl,c) —C3-10 cycloalkyl,d) -heterocyclyl,e) -phenyl,f) -heteroaryl,g) -cyano,h) —CF3,i) —OCF3,j) —O—Rf,k) —S(O)w—Rf,l) —S(O)2O—Rf,m) —NRfRg,n) —C(O)—Rf,o) —C(O)—O—Rf,p) —OC(O)—Rf,q) —C(O)NRf Rg,r) —C(O)-heterocyclyl,s) —NRf C(O)Rg,t) —OC(O)NRf Rg,u) —NRf C(O)ORf, orv) —NRf C(O)NRf Rg,where the alkyl, cycloalkyl, heterocyclyl, phenyl, and heteroaryl groups are optionally substituted one or more times with substituents independently selected from Rz; Rc is a) -halogen,b) —C1-6 alkyl,c) —C3-10 cycloalkyl,d) -heterocyclyl,e) -cyano,f) —CF3,g) —OCF3,h) —O—Rh,i) —S(O)w—Rh,j) —S(O)2O—Rh,k) —NRhRk,l) —C(O)—Rh,m) —C(O)—O—Rh,n) —OC(O)—Rh,o) —C(O)NRhRk,p) —C(O)-heterocyclyl,q) —NRh C(O)Rk,r) —OC(O)NRh Rk,s) —NRh C(O)ORk,t) —NRh C(O)NRh Rk,u) —NRh S(O)wRk,v) -phenyl,w) -heteroaryl, orx) —O—(C1-4 alkylene)-O—(C1-4 alkylene)-N(Rh)C(O)—ORk,where the alkylene, alkyl, cycloalkyl, heterocyclyl, phenyl, and heteroaryl groups are optionally substituted one or more times with substituents independently selected from Rx; Rd and Re are independently hydrogen, C1-6 alkyl, or C3-10 cycloalkyl, where the alkyl and cycloalkyl groups are optionally substituted one or more times with substituents independently selected from Ry; or, if Rd and Re are both attached to the same nitrogen atom, together with that nitrogen atom may optionally form a heterocyclic ring selected from the group consisting of azetidino, pyrrolidino, pyrazolidino, imidazolidino, oxazolidino, isoxazolidino, thiazolidino, isothiazolidino, piperidino, piperazino, morpholino, thiomorpholino, and azepano, where each ring is optionally substituted one or more times with substituents independently selected from Ry; Rf and Rg are independently hydrogen, C1-6 alkyl, C3-10 cycloalkyl, phenyl, or heteroaryl, where the alkyl, cycloalkyl, phenyl, and heteroaryl groups are optionally substituted one or more times with substituents independently selected from Rz; or, if Rf and Rg are both attached to the same nitrogen atom, together with that nitrogen atom may optionally form a heterocyclic ring selected from the group consisting of azetidino, pyrrolidino, pyrazolidino, imidazolidino, oxazolidino, isoxazolidino, thiazolidino, isothiazolidino, piperidino, piperazino, morpholino, thiomorpholino, and azepano, where each ring is optionally substituted one or more times with substituents independently selected from Rz; Rh and Rk are independently hydrogen, C1-6 alkyl, C3-10 cycloalkyl, heterocyclyl, phenyl, or heteroaryl, where the alkyl, cycloalkyl, heterocyclyl, phenyl, and heteroaryl groups are optionally substituted one or more times with substituents independently selected from Rx; or, if Rh and Rk are both attached to the same nitrogen atom, together with that nitrogen atom may optionally form a heterocyclic ring selected from the group consisting of azetidino, pyrrolidino, pyrazolidino, imidazolidino, oxazolidino, isoxazolidino, thiazolidino, isothiazolidino, piperidino, piperazino, morpholino, thiomorpholino, and azepano, where each ring is optionally substituted one or more times with substituents independently selected from Rx; Ry is a) -halogen,b) —NH2,c) -cyano,d) -carboxy,e) -hydroxy,f) -thiol,g) —CF3,h) —OCF3,i) —C(O)—NH2,j) —S(O)2—NH2,k) oxo,l) —C1-6 alkyl, optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C1-6 alkyl, —NH2, —NH—C1-6 alkyl, and —N(C1-6 alkyl)2,m) -heterocyclyl optionally substituted one or more times with one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C1-6 alkyl, —NH2, —NH—C1-6 alkyl, and —N(C1-6 alkyl)2,n) —C3-10 cycloalkyl optionally substituted one or more times with one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C1-6 alkyl, —NH2, —NH—C1-6 alkyl, and —N(C1-6 alkyl)2,o) —O—C1-6 alkyl optionally substituted one or more times with one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C1-6 alkyl, —NH2, —NH—C1-6 alkyl, and —N(C1-6 alkyl)2,p) —O—C3-10 cycloalkyl optionally substituted one or more times with one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C1-6 alkyl, —NH2, —NH—C1-6 alkyl, and —N(C1-6 alkyl)2,q) —NH—C1-6 alkyl optionally substituted one or more times with one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C1-6 alkyl, —NH2, —NH—C1-6 alkyl, and —N(C1-6 alkyl)2,r) —N(C1-6 alkyl)2 optionally substituted one or more times with one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C1-6 alkyl, —NH2, —NH—C1-6 alkyl, and —N(C1-6 alkyl)2,s) —C(O)—C1-6 alkyl, optionally substituted one or more times with one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C1-6 alkyl, —NH2, —NH—C1-6 alkyl, and —N(C1-6 alkyl)2,t) —C(O)—O—C1-6 alkyl, optionally substituted one or more times one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C1-6 alkyl, —NH2, —NH—C1-6 alkyl, and —N(C1-6 alkyl)2,u) —S—C1-6 alkyl, optionally substituted one or more times with one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C1-6 alkyl, —NH2, —NH—C1-6 alkyl, and —N(C1-6 alkyl)2,v) —S(O)2—C1-6 alkyl, optionally substituted one or more times one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C1-6 alkyl, —NH2, —NH—C1-6 alkyl, and —N(C1-6 alkyl)2,w) —C(O)—NH—C1-6 alkyl, optionally substituted one or more times one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C1-6 alkyl, —NH2, —NH—C1-6 alkyl, and —N(C1-6 alkyl)2,x) —C(O)—N(C1-6 alkyl)2, optionally substituted one or more times one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C1-6 alkyl, —NH2, —NH—C1-6 alkyl, and —N(C1-6 alkyl)2,y) —S(O)2—NH—C1-6 alkyl, optionally substituted one or more times one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C1-6 alkyl, —NH2, —NH—C1-6 alkyl, and —N(C1-6 alkyl)2,z) —S(O)2—N(C1-6 alkyl)2, optionally substituted one or more times one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C1-6 alkyl, —NH2, —NH—C1-6 alkyl, and —N(C1-6 alkyl)2,aa) —NH—C(O)—C1-6 alkyl, optionally substituted one or more times one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C1-6 alkyl, —NH2, —NH—C1-6 alkyl, and —N(C1-6 alkyl)2, orbb) —NH—S(O)2—C1-6 alkyl, optionally substituted one or more times one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C1-6 alkyl, —NH2, —NH—C1-6 alkyl, and —N(C1-6 alkyl)2; Rx is a) —Ryb) -phenyl, optionally substituted one or more times with one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C1-6 alkyl, —NH2, —NH—C1-6 alkyl, and —N(C1-6 alkyl)2,c) -heteroaryl, optionally substituted one or more times with one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C1-6 alkyl, —NH2, —NH—C1-6 alkyl, and —N(C1-6 alkyl)2,d) —O-phenyl,e) —O-heteroaryl,f) —C(O)-phenyl,g) —C(O)-heteroaryl,h) —C(O)—O-phenyl, ori) —C(O)—O-heteroaryl; Rz is a) —Ryb) -phenyl,c) -heteroaryl;d) —O-phenyl,e) —O-heteroaryl,f) —C(O)-phenyl,g) —C(O)-heteroaryl,h) —C(O)—O-phenyl, ori) —C(O)—O-heteroaryl; v is an integer from 0 to 4, and w is an integer from 0 to 2.
地址 High Point NC US