Substituted triazoles as angiotensin II antagonists

Claim 1

A compound of formula (I): wherein: R¹ is (a) -CO₂R⁴, (b) -SO₃R⁵, (c) -NHSO₂CF₃, (d) -PO(OR⁵)₂, (e) -SO₂-NH-R⁹, (f) -SO₂NH-heteroaryl as defined below, (g) -CH₂SO₂NH-heteroaryl as defined below, (h) -SO₂NH-CO-R²³, (i) -CH₂SO₂NH-CO-R²³, (j) -CONH-SO₂R²³, (k) -CH₂CONH-SO₂R²³, (l) -NHSO₂NHCO-R²³, (m) -NHCONHSO₂-R²³, wherein: heteroaryl is an unsubstituted, monosubstituted or disubstituted five or six membered aromatic ring which can optionally contain from 1 to 3 heteroatoms selected from the group consisting of O, N or S and wherein the substituents are members selected from the group consisting of -OH, -SH, -C₁-C₄-alkyl, -C₁-C₄-alkoxy, -CF₃, halo (Cl, Br, F, I), -NO₂, -CO₂H, -CO₂-C₁-C₄-alkyl, -NH₂, -NH(C₁-C₄-alkyl) and -N(C₁-C₄-alkyl)₂; Y is (1) -CO₂R⁴, (2) -SO₃R⁵, (3) -NHSO₂CF₃, (4) -PO(OR⁵)₂, (5) -SO₂-NH-R⁹, or (6) 1 H -tetrazol-5-yl; R 2a and R 2b are each independently: (a) hydrogen, (b) halogen (Cl, Br, I, F) (c) -NO₂, (d) NH₂, (e) C₁-C₄-alkylamino, (f) -SO₂NHR⁹, (g) CF₃, (h) C₁-C₄-alkyl, (i) C₁-C₄-alkoxy, or (j) R 2a and R 2b on adjacent carbons are bonded together to form a phenyl ring; R 3a is (a) H, (b) halo (Cl, Br, I, F) (c) C₁-C₆-alkyl, (d) C₁-C₆-alkoxy, (e) C₁-C₆-alkoxy-C₁-C₄-alkyl; R 3b is (a) H, (b) halo (Cl, Br, I, F) (c) NO₂, (d) C₁-C₆-alkyl, (e) C₁-C₅-alkylcarbonyloxy, (f) C₃-C₆-cycloalkyl (g) C₁-C₆-alkoxy, (h) -NHSO₂R⁴, (i) hydroxy-C₁-C₄-alkyl, (j) aryl C₁-C₄-alkyl (k) C₁-C₄-alkylthio (l) C₁-C₄-alkylsulfinyl (m) C₁-C₄-alkylsulfonyl (n) NH₂ (o) C₁-C₄-alkylamino (p) C₁-C₄-dialkylamino (g) CF₃, (r) -SO₂-NHR⁹ (s) aryl, (t) furyl, or (u) R 3a and R 3b on adjacent carbons are bonded together to form a phenyl ring; wherein aryl is phenyl or naphthyl optionally substituted with one or two substituents selected from the group consisting of halo (Cl, Br, I, F), C₁-C₄-alkyl, C₁-C₄-alkoxy, NO₂, CF₃, C₁-C₄-alkylthio, OH or NH₂; R⁴ is H, straight chain or branched C₁-C₆ alkyl, benzyl or phenyl; R⁵ is H, E is a single bond, -NR¹³(CH₂) s -, -S(O) x (CH₂) s - where x is 0 to 2 and s is 0 to 5, -CH(OH)-, -O(CH₂) s -, -CO-; R⁶ is (a) aryl as defined above optionally substituted with 1 or 2 substituents selected from the group consisting of halo (Cl, Br, I, F), -O-C₁-C₄-alkyl, C₁-C₄-alkyl, -NO₂, -CF₃, -SO₂NR⁹R¹⁰, -S-C₁-C₄-alkyl, -OH, -NH₂, C₃-C₇-cycloalkyl, C₂-C₁₀-alkenyl; (b) straight chain or branched C₁-C₆-alkyl, C₂-C₆-alkenyl or C₂-C₆-alkynyl each of which can be optionally substituted with a substituent selected from the group consisting of aryl as defined above, -O-C₁-C₄-alkyl, C₃-C₇-cycloalkyl, halo (Cl, Br, I, F), -OH, -NH₂, -NH(C₁-C₄-alkyl), -N(C₁-C₄-alkyl)₂, -NH-SO₂R⁴, -COOR⁴, -SO₂NHR⁹, -S-C₁-C₄-alkyl; (c) an unsubstituted, monosubstituted or disubstituted aromatic 5 or 6 membered ring which can contain one or two members selected from the group consisting of N, O, S, and wherein the substituents are members selected from the group consisting of -OH, -SH, C₁-C₄-alkyl, C₁-C₄-alkyloxy -CF₃, halo (Cl, Br, I, F), or NO₂; (d) mono-, di-, tri- or polyfluoro-C₁-C₅-alkyl; (e) C₃-C₇-cycloalkyl optionally substituted with one or more substituents selected from the group consisting of C₁-C₄-alkyl, -O-C₁-C₄-­alkyl, -S-C₁-C₄-alkyl, -OH, perfluoro-C₁-C₄-­alkyl or halo (Cl, Br, F, I); (f) C₃-C₇-cycloalkyl-C₁-C₃-alkyl wherein the cycloalkyl is substituted as in (e) above; A is S(O) p , -O- or NH wherein p is 0 to 2; R⁷ is (a) C₁-C₁₀-alkyl; (b) substituted C₁-C₁₀ alkyl in which one or more substituent(s) is selected from (1) halogen, (2) hydroxy, (3) C₁-C₁₀-alkoxy, (4) C₁-C₅-alkoxycarbonyl, (5) C₁-C₄-alkylcarbonyloxy, (6) C₃-C₈-cycloalkyl, (7) aryl, (8) substituted aryl in which the substituents are V and W, (9) C₁-C₁₀-alkyl-S(O) p , (10) C₃-C₈-cycloalkyl-S(O) p , (11) phenyl-S(0) p , (12) substituted phenyl-S(O) p in which the substituents are V and W, (13) oxo, (14) carboxy, (15) NR⁹R¹⁰, (16) C₁-C₅-alkylaminocarbonyl, (17) di(C₁-C₅-alkyl)aminocarbonyl, (18) cyano; (c) perfluoro-C₁-C₄-alkyl, (d) C₂-C₁₀-alkenyl, (e) C₂-C₁₀-alkynyl, (f) C₃-C₈-cycloalkyl, (g) substituted C₃-C₈-cycloalkyl in which one or more substituent(s) is selected from: (1) halogen, (2) hydroxy, (3) C₁-C₁₀-alkoxy, (4) C₁-C₅-alkoxycarbonyl, (5) C₁-C₄-alkylcarbonyloxy, (6) C₃-C₈-cycloalkyl, (7) aryl, (8) substituted aryl in which the substituents are V and W, (9) C₁-C₁₀-alkyl-S(O) p in which p is 0 to 2, (10) C₃-C₈-cycloalkyl-S(O) p , (11) phenyl-S(O) p , (12) substituted phenyl-S(O) p in which the substituents are V and W, (13) oxo, (14) carboxy, (15) NR⁹R¹⁰, (16) C₁-C₅-alkylaminocarbonyl, (17) di(C₁-C₅-alkyl)aminocarbonyl, (18) cyano, (19) C₁-C₄-alkylcarbonyl; (h) aryl, (i) substituted aryl in which the substituents are V and W, (j) aryl-(CH₂) r -(B) b -(CH₂) t -, (k) substituted aryl-(CH₂) r -(B) b -(CH₂) t - in which the aryl group is substuted with V and W; (l) a heterocyclic ring of 5 to 6 atoms containing one or two heteroatoms selected from: with the proviso that when E is a single bond and n is 0, then R⁷ is: (a) substituted C₁-C₁₀-alkyl in which one or more substituent(s) is selected from: (1) C₃-C₈-cycloalkyl, (2) aryl as defined above, (3) substituted aryl as defined above in which the substituents are V and W, (4) C₃-C₈-cycloalkyl-S(O) p where p is 0 to 2, (5) phenyl-S(O) p where p is 0 to 2, (6) substituted phenyl-S(O) p where p is 0 to 2 and the substituents are V and W: (b) CF₃; (c) C₃-C₈-cycloalkyl; (d) substituted C₃-C₈-cycloalkyl in which the substituent is selected from: (1) C₁-C₅-alkyl, (2) C₁-C₅-alkoxy; (e) aryl as defined above; (f) substituted aryl as defined above in which the substituents are V and W; (g) aryl-(CH₂) r -(B) b -(CH₂) t - in which b is 0 when B is -C(O)-; (h) substituted aryl-(CH₂) r -(B) b -(CH₂) t - in which b is 0 when B is -C(O)- and the aryl group is substituted with V and W; (i) a heterocyclic ring of 5 to 6 atoms containing one or two heteroatoms, said heterocyclic ring being selected from: n is 0 or 1; B is -C(O)-, -S-, or -O-, -NR⁴, -NR⁴C(O)-, or -C(O)NR⁴; b is 0 or 1; r and t are 0 to 2; u is 1 or 2; p is 0 to 2; V and W are each independently selected from: (a) H, (b) C₁-C₅-alkoxy, (c) C₁-C₅-alkyl, (d) hydroxy, (e) C₁-C₅-alkyl-S(O) p , (f) -CN, (g) -NO₂, (h) -NR⁹R¹⁰; (i) C₁-C₄-alkyl-CONR⁹R¹⁰, (j ) -CO₂R⁹, (k) C₁-C₅-alkyl-carbonyl, (l) trifluoromethyl, (m) halogen, (n) hydroxy-C₁-C₄-alkyl, (o) C₁-C₄-alkyl-CO₂R⁹, (p) -1 H -tetrazol-5-yl, (q) -NHSO₂CF₃, (r) aryl as defined above, (s) -OCONR⁹R¹⁰, (t) -NR⁴CO₂R⁹, (u) -NR⁴CONR⁹R¹⁰, (v) -NR⁴CON(CH₂CH₂)₂Q where Q is O, S(O) p or NR⁹, (w) -OCON(CH₂CH₂)₂Q where Q is as defined above; (x) -CONR⁹R¹⁰; R⁹ is H, C₁-C₅-alkyl, phenyl or benzyl; R¹⁰ is H, C₁-C₄-alkyl; or, R⁹ and R¹⁰ together may be -(CH₂) m - where m is 3-6; R¹¹ is H, C₁-C₆-alkyl, C₂-C₄-alkenyl, C₁-C₄-alkoxy-­C₁-C₄-alkyl, or -CH₂-C₆H₄R²⁰; R¹² is -CN, -NO₂ or -CO₂R⁴; R¹³ is H, C₁-C₄-acyl, C₁-C₆-alkyl, allyl, C₃-C₆-cycloalkyl, phenyl or benzyl; R¹⁴ is H, C₁-C₈-alkyl, C₁-C₈-perfluoroalkyl, C₃-C₆-cycloalkyl, phenyl or benzyl; R¹⁵ is H, C₁-C₆-alkyl, hydroxy; R¹⁶ is H, C₁-C₆-alkyl, C₃-C₆-cycloalkyl, phenyl or benzyl; R¹⁷ is -NR⁹R¹⁰, -OR¹⁰, -NHCONH₂, -NHCSNH₂, -NHSO₂CF₃; R¹⁸ and R¹⁹ are independently C₁-C₄-alkyl or taken together are -(CH₂) q - where q is 2 or 3; R²⁰ is H, -NO₂, -NH₂, -OH or -OCH₃; R²¹ is C₁-C₅ alkyl or CF₃; R²³ is (a) aryl as defined above, (b) heteroaryl as defined above, (c) C₃-C₇-cycloalkyl, (d) C₁-C₄-alkyl optionally substituted with a substituent selected from the group consisting of aryl as defined above, heteroaryl as defined above, -OH, -SH, C₁-C₄-alkyl, -O(C₁-C₄-alkyl), -S(C₁-C₄-alkyl), -CF₃, halo (Cl, Br, F, I), -NO₂, -CO₂H, -CO₂-C₁-C₄-alkyl, -NH₂, -NH(C₁-C₄-alkyl), -N(C₁-C₄-alkyl)₂, -N(CH₂CH₂)₂L where L is a single bond, CO₂, O, S(O) p or NR⁹, -PO₃H, -PO(OH)(O-C₁-C₄-alkyl); X is (a) a carbon-carbon single bond, (b) -CO-, (c) -O-, (d) -S-, (h) -OCH₂-, (i) -CH₂O- (j) -SCH₂-, (k) -CH₂S-, (l) -NHC(R⁹)(R¹⁰)-, (m) -NR⁹SO₂-, (n) -SO₂NR⁹-, (o) -C(R⁹)(R¹⁰)NH-, (p) -CH=CH-, (q) -CF=CF-, (r) -CH=CF-, (s) -CF=CH-, (t) -CH₂CH₂-, (u) -CF₂CF₂-, (v) 1,1 and 1,2-disubstituted cyclopropyl, Z is O, NR¹³ or S; and, the pharmaceutically acceptable salts thereof.