Imidazole derivatives bearing acidic functional groups at the 5-position, their compositions and methods of use as angiotensin II antagonists

Claim 1

A compound of structural formula I ##STR46## or a pharmaceutically acceptable salt thereof wherein: R 1 is (a) --CO 2 R 10 , (b) --NHSO 2 R 12 , (c) --SO 2 NHR 12 , ##STR47## (g) --CONHNHSO 2 CF 3 , (h) --CH 2 SO 2 NHR 12 , (i) --SO 2 NHCOR 12 , (j) --CH 2 SO 2 NHCOR 12 , (k) --CONHSO 2 R 12 , (l) --CH 2 CONHSO 2 R 12 , (m) --NHSO 2 NHCOR 12 , (n) --NHCONHSO 2 R 12 , (o) --SO 2 NHCONR 2a R 12 , or (p) --CONHSO 2 NR 2a R 12 ; R 2 is: (a) H, or (b) (C 1 -C 6 )-alkyl; R 2a is: (a) R 2 , (b) --CH 2 -aryl, wherein aryl is phenyl or naphthyl unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of: i) Cl, Br, I, F, ii) (C 1 -C 4 )-alkyl, iii) (C 1 -C 4 )-alkoxy, iv) NO 2 , v) CF 3 , vi) (C 1 -C 4 )-alkylthio, vii) hydroxy, viii) amino, ix) (C 3 -C 7 )-cycloalkyl, x) (C 3 -C 10 )-alkenyl, or xi) CN, or (c) aryl as defined in R 2a (b) above; R 3 is: (a) --SO 2 NHR 12 , (b) --CH 2 SO 2 NHR 12 , (c) --SO 2 NHCOR 12 , (d) --CH 2 SO 2 NHCOR 12 , (e) --CONHSO 2 R 12 , (f) --CH 2 CONHSO 2 R 12 , (g) --NHSO 2 NHCOR 12 , (h) --NHCONHSO 2 R 12 , (i) --SO 2 NHCONR 2a R 12 , (j) --CONHSO 2 NR 2a R 12 , or (k) --NHSO 2 R 12 ; y is 0 or 1; R 4 is: (a) H, (b) (C 1 -C 8 )-alkyl, (C 2 -C 6 )-alkenyl or (C 2 -C 6 )-alkynyl, (c) Cl, Br, I, F, (d) NO 2 , (e) (C 1 -C 8 )-perfluoroalkyl, (f) (C 1 -C 8 )-perfluoroalkenyl, (g) pentafluorophenyl, (h) CN, (i) phenyl, (j) phenyl-(C 1 -C 3 )-alkyl, (k) phenyl and phenyl-(C 1 -C 3 )-alkyl substituted on the phenyl ring with one or two substituents selected from: i) (C 1 -C 4 )-alkyl, ii) (C 1 -C 4 )-alkoxy, iii) F, Cl, Br, I, iv) hydroxy, v) CF 3 , vi) CO 2 R 2a , vii) NO 2 , or viii) SO 2 NR 2a R 2a ; (1) phenyl-(C 2 -C 6 )-alkenyl, ##STR48## (n) --(CH 2 ) n --S(O) x R 15 , ##STR49## (u) --(CH 2 ) n --NHSO 2 R 16 , or (v) --(CH 2 ) n --F; R 5 is: (a) (C 1 -C 9 )-alkyl, (C 2 -C 6 )-alkenyl or (C 2 -C 6 )-alkynyl each of which is unsubstituted or substituted with a substituent selected from the group consisting of: i) aryl as defined in R 2a (b) above, ii) (C 3 -C 7 )-cycloalkyl, iii) Cl, Br, I, F, iv) COOR 2 , vii) N((C 1 -C 4 )-alkyl) 2 , viii) NHSO 2 R 2 , ix) CF 3 , x) COOR 2 , or xi) SO 2 NHR 2a , (b) aryl, or (d) (C 1 -C 4 )-perfluoroalkyl; B is a single bond; x is 0 to 2; s is 0 to 5; m is 1 to 5; p is 0 to 3; n is 1 to 10; R 6 is: (a) H, (b) Cl, Br, I, F, (c) (C 1 -C 6 )-alkyl, (d) (C 1 -C 6 )-alkoxy, or (e) (C 1 -C 6 )-alkoxyalkyl; R 7 is: (a) H, (b) Cl, Br, I, F, (c) NO 2 , (d) (C 1 -C 6 )-alkyl, (e) (C 1 -C 6 )-acyloxy, (f) (C 3 -C 6 )-cycloalkyl, (g) (C 1 -C 6 )-alkoxy, (h) --NHSO 2 R 2a , (i) hydroxy (C 1 -C 4 )-alkyl, (j) (C 1 -C 4 )-alkyl-aryl, (k) aryl-(C 1 -C 4 )-alkyl, (l) (C 1 -C 4 )-alkylthio, (m) (C 1 -C 4 )-alkylsulfinyl, (n) (C 1 -C 4 )-alkylsulfonyl, (o) NH 2 , (p) NH((C 1 -C 4 )-alkyl), (q) NH((C 1 -C 4 )-alkyl) 2 , (r) (C 1 -C 4 )-fluoroalkyl, (s) --SO 2 --NHR 10 , (t) aryl, (u) furyl, or (v) --COOR 11 ; R 8 and R 9 are independently: H, Cl, Br, I, F, --NO 2 , --NH 2 , NH((C 1 -C 4 )-alkyl), N((C 1 -C 4 ) alkyl) 2 , --SO 2 NHR 10 , CF 3 , (C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkoxy, (C 2 -C 6 )-alkenyl, (C 2 -C 6 )-alkynyl or when R 8 and R 9 are on adjacent carbon atoms, they are joined to form an aryl ring; R 10 is: H, (C 1 -C 5 )-alkyl, aryl or --CH 2 -aryl, wherein aryl is as defined in R 2a (b); R 11 is ##STR50## R 12 is: (a) aryl as defined in R 2a (b), (b) heteroaryl, wherein heteroaryl is defined as an unsubstituted, monosubstituted or disubstituted hetero aromatic ring selected from the group consisting of: isoxazolyl, and pyrimidyl, wherein the substituents are members selected from the group consisting of: --OH, --SH, --(C 1 -C 4 )-alkyl, --(C 1 -C 4 )-alkoxy, --CF 3 , Cl, Br, F, I, --NO 2 , --CO 2 H, --CO 2 --(C 1 -C 4 )-alkyl, --NH 2 , --NH((C 1 -C 4 )-alkyl), or --N((C 1 -C 4 )-alkyl) 2 , (c) (C 3 -C 4 )-cycloalkyl, (d) (C 1 -C 4 )-alkyl which is unsubstituted or substituted with a substituent selected from the group consisting of: aryl as defined in R 2a (b), heteroaryl as defined above in R 12 (b), --OH, --SH, (C 1 -C 4 )-alkyl, --O--(C 1 -C 4 )-alkyl --S(O) x --(C 1 -C 4 )-alkyl, --CF 3 , Cl, Br, F, I, --NO 2 , --CO 2 H, --CO 2 --(C 1 -C 4 )-alkyl, --NH 2 , --NH[(C 1 -C 4 )-alkyl], --NHCOR 2a , or --N[(C 1 -C 4 )-alkyl] 2 , or (e) (C 1 -C 4 )-perfluoroalkyl; R 13 is: (a) H, (b) (C 1 -C 6 )-alkyl, (c) aryl as defined in R 2a (b), (d) aryl-(C 1 -C 6 )-alkyl-(C═O)--, wherein aryl is as defined in R 2a (b), (e) (C 1 -C 6 )-alkyl-(C═O)--, (f) (C 3 -C 6 )-cycloalkyl, or (g) allyl; R 14 is: (a) H, (b) (C 1 -C 8 )-alkyl, (c) phenyl, or (d) benzyl; R 15 is: (a) H, (b) (C 1 -C 6 )-alkyl, (c) (C 3 -C 6 )-cycloalkyl, (d) --(CH 2 ) p -phenyl, (e) --OR 17 , (f) morpholin-4-yl, or (g) --NR 18 R 19 ; R 16 is: (a) (C 1 -C 8 )-alkyl, (b) (C 1 -C 8 )-perfluoroalkyl, (c) 1-adamantyl, (d) 1-naphthyl, (e) (1-naphthyl)ethyl, or (f) --(CH 2 ) p -phenyl; R 17 is: (a) H, (b) (C 1 -C 6 )-alkyl, (c) (C 3 -C 6 )-cycloalkyl, (d) phenyl, or (e) benzyl; R 18 and R 19 are independently: (a) H, (b) (C 1 -C 4 )-alkyl, (c) phenyl, (d) benzyl, or (e) α-methylbenzyl; R 20 is: (a) H, (b) (C 1 -C 6 )-alkyl, (c) (C 3 -C 6 )-cycloalkyl, or (d) --CH 2 -aryl; R 21 is: (a) H, (b) (C 1 -C 6 )-alkyl, (c) (C 2 -C 4 )-alkenyl, or (d) (C 1 -C 4 )-alkoxy-(C 1 -C 4 )-alkyl; R 22 is: (a) CN, (b) NO 2 , or (c) COOR 10 ; and X is a carbon-carbon single bond.