Substituted imidazo-fused 5-membered ring heterocycles as angiotensin II antagonists

Claim 1

A compound having the formula: wherein: R¹ is (a) -CO₂R⁴, (b) -SO₃R⁵, (c) -NHSO₂CF₃, (d) -PO(OR⁵)₂, (e) -SO₂-NH-R⁹, (g) -SO₂NH-heteroaryl as defined below, (h) -CH₂SO₂NH-heteroaryl as defined below, (i) -SO₂NH-CO-R²¹ (j) -CH₂SO₂NH-CO-R²¹, (k) -CONH-SO₂R²¹, (l) -CH₂CONH-SO₂R²¹, (m) -NHSO₂NHCO-R²¹, (n) -NHCONHSO₂R²¹, (o) -SO₂NHCONHR²¹, 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; R 2a and R 2b are independently H, halo (Cl, Br, I, F), -NO₂, -NH₂, C₁-C₄-alkylamino, di(C₁-C₄-alkyl)­amino, -SO₂NHR⁹, CF₃, C₁-C₄-alkyl, or C₁-C₄-alkoxy; 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-C₆-acyloxy, (f) C₃-C₇-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) di(C₁-C₄-alkyl)amino (g) CF₃ (r) -SO₂-NHR⁹ (s) aryl or, (t) furyl; wherein aryl is phenyl or naphthyl optionally substituted with one or two substituents selected from V and W as defined below; R⁴ is H, straight chain or branched C₁-C₆-alkyl, aryl, or aryl-C₁-C₅-alkyl wherein the aryl groups are as defined above and where a substituent, can be the same or different; R 4a is C₁-C₆-alkyl, aryl or aryl-C₁-C₅-alkyl; R⁵ is H or CH(R⁴)-O-CO-R 4a ; 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-, -CO-; R⁶ is (a) aryl as defined above; (b) straight chain or branched C₁-C₆-alkyl, C₃-C₇-cycloalkyl, C₂-C₅-alkenyl or C₂-C₅-alkynyl each of which can be optionally substituted with a substituent selected from the group consisting of aryl as defined above, C₃-C₇-cycloalkyl, halo (Cl, Br, I, F) -OH, -NH₂, -NH(C₁-C₄-alkyl), -N(C₁-C₄-alkyl)₂, -NH-SO₂R₄, -COOR⁴, -SO₂NHR⁹; or (c) an unsubstituted, monosubstituted or disubstituted hetero aromatic 5 or 6 membered ring which can contain one or two heteroatoms 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), -CO₂R⁴, or NO₂; A-B-C together are: (a) -N(R⁸)-C(R 7a )=N- (b) -N=C(R 7a )-N(R⁸)- (c) -C(R 7a )=N-N(R⁸)- (d) -N(R⁸)-N=C(R 7a )- (e) -Y-C(R 7a )=N- (f) -N=C(R 7a )-Y- (g) -C(R 7a )=N-Y- (h) -Y-N=C(R 7a )- (i) =N-Y-C(R 7a )= (j) =C(R 7a )-Y-N= (k) -C(R 7a )=C(R 7b )-N(R⁸)- (l) -C(R 7a )=C(R 7b )-Y- (m) -N(R⁸)-C(R 7a )=C(R 7b )- (n) -Y-C(R 7a )=C(R 7b )- (o) =C(R 7a )-N(R⁸)-C(R 7b )= (p) =C(R 7a )-Y-C(R 7b )= (q) =N-Y-N= (r) -N=N-N(R⁸)- (s) -N(R⁸)-N=N- (t) =N-N(R⁸)-N= (u) =N-N(R⁸)-C(R 7a )= (v) =C(R 7a )-N(R⁸)-N= (w) -C(R 7c )(R 7d )-O-C(=O)- (x) -C(R 7c )(R 7d )-C(=O)-O- (y) -O-C(=O)-C(R 7c )(R 7d )- (z) -C(=O-)O-C(R 7c )(R 7d )- (aa) -C(=O)-N(R⁸)-C(R 7c )(R 7d )- (bb) -C(R 7c )(R 7d )-N(R⁸)-C(=O)- Y is O, S, SO or SO₂ R 7a and R 7b are independently (a) H, (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 C₃-C₇-cycloalkyl, halo (Cl, Br, I, F), -OH, -NH₂, -NH(C₁-C₄-alkyl), -N(C₁-C₄ alkyl)₂, -NHSO₂R⁴, -COOR⁴, C₁-C₄-­alkoxyl, C₁-C₄-alkylthio, C₁-C₄-­alkylcarbonyl, -CONH₂, -OCOR⁴, -CON(R⁴)₂, aryl, -S(O) x -R²¹, tetrazol-5-yl, -CONHSO₂R²¹, -SO₂NH-hetroaryl wherein the heteroaryl is as first defined above, -SO₂NHCO-R²¹, heteroaryl as first defined above, -PO(OR⁴)₂, -PO(OR⁴)R⁹, (c) aryl as defined above, (d) substituted aryl in which the substituents are V or W, as defined below, (e) aryl-C₁-C₄-alkyl in which the aryl group as defined above can be unsubstituted or substituted with V or W as defined below, (f) halo, (g) hydroxy, (h) -N(R⁴)R²¹, (i) C₁-C₆-alkoxy, (j) perfluoro-C₁-C₄-alkyl, (k) CO₂R⁴, (l) CON(R⁴)₂, (m) N(R⁴)-CO-R⁴, (n) -S(O) x -R²¹, (p) tetrazol-5-yl, (q) -CN, (r) -CONHSO₂R²¹, (s) -SO₂NH-heteroaryl, (t) -SO₂NHCOR²¹, (u) heteroaryl, (v) -NHSO₂R²¹, (w) -NHSO₂CF₃, R 7c and R 7d are independently (a) H (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 C₃-C₇-cycloalkyl, halo (Cl, Br, I, F), -OH, -NH₂, -NH(C₁-C₄-alkyl), -N(C₁-C₄-alkyl)₂, -NHSO₂R⁴, -COOR⁴, C₁-C₄-­alkoxy, C₁-C₄-alkylthio, C₁-C₄-­alkylcarbonyl, or -CONH₂, (c) aryl as defined above, (d) substituted aryl as defined above in which the substituents are V or W as defined below, (e) aryl-C₁-C₄-alkyl in which the aryl group is as defined above and which can be unsubstituted or substituted with V or W as defined below; R⁸ is: (a) H, (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 C₃-C₇-cycloalkyl, halo (Cl, Br, I, F), -OH, -NH₂, -NH(C₁-C₄-alkyl), -N(C₁-C₄-alkyl)₂, -NHSO₂R⁴, -COOR⁴, C₁-C₄-alkoxyl, C₁-C₄-alkylthio, -CONH₂, -COR⁴, or -SO₂R⁴, (c) -COR⁴ (d) aryl, or substituted aryl wherein the aryl groups are as defined above and the substituents are V or W as defined below, (e) aryl-C₁-C₄-alkyl in which the aryl group is as defined above and can be unsubstituted, mono-or di-substituted with V or W as defined below; V and W are independently: (a) H, (b) C₁-C₅-alkoxy, (c) C₁-C₅-alkyl, (d) hydroxy, (e) C₁-C₅-alkyl-S(O) x - where x is as defined above, (f) CN, (g) NO₂, (h) NHR⁴, (i) N(R⁴)₂, (j) CON(R⁴)₂, (k) CO₂R⁴, (l) COR⁴, (m) CF₃, (n) halo (Cl, Br, I, F), (o) hydroxy-C₁-C₅-alkyl, (p) C₁-C₅-alkylthio, (q) -SO₂NR⁹R¹⁰, (r) C₃-C₇-cycloalkyl, (s) C₂-C₁₀-alkenyl, R⁹ is H, C₁-C₅-alkyl, phenyl or benzyl; R¹⁰ is H, C₁-C₄-alkyl; R¹¹ is H, C₁-C₆alkyl, 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; R¹⁶ is H, C₁-C₆-alkyl, C₃-C₆-cycloalkyl, phenyl or benzyl; 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 (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, -PO₃H, -PO(OH)(O-C₁-C₄-alkyl); (e) perfluoro -C₁-C₄-alkyl; X is: (a) a 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-, Z is O, NR¹³ or S; r is 1 or 2; and, the pharmaceutically acceptable salts thereof.