Substituted imidazo-fused 6-membered heterocycles as angiotensin II antagonists

Claim 1

A compound of structural formula: wherein: R¹ is (a) -CO₂R⁴, (b) -SO₃R⁵, (c) -NHSO₂CF₃, (d) -PO(OR⁵)₂, (e) -SO₂-NH-R⁹, (f) -CONH0R⁵, (h) -SO₂NH-heteroaryl, (i) -CH₂SO₂NH-heteroaryl, (j) -SO₂NHCO-R²³, (k) -CH₂SO₂NHCO-R²³, (l) -CONH-SO₂R²³, (m) -CH₂CONH-SO₂R²³, (n) -NHSO₂NHCO-R²³, (o) -NHCONHSO₂-R²³, (p) -SO₂NHCONR²³, wherein heteroaryl is an unsubstituted, monosubstituted or disubstituted five- or six-membered aromatic ring which can optionally contain 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, 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-alkoxyalkyl; R 3b is (a) H, (b) halo (Cl, Br, I, F) (c) NO₂, (d) C₁-C₆-alkyl, (e) C₁-C₆-acyloxy, (f) C₁-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-alkyl sulfinyl (m) C₁-C₄-alkyl sulfonyl (n) NH₂ (o) C₁-C₄-alkylamino (p) C₁-C₄-dialkylamino (q) fluoro C₁-C₄-alkyl (r) -SO₂-NHR⁹ (s) aryl or, (t) furyl; 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, NH₂, NH(C₁-C₄-alkyl), N(C₁-C₄-alkyl)₂, CO₂H, and CO₂-C₁-C₄-alkyl; R⁴ is H, straight chain or branched C₁-C₆ alkyl, aryl or -CH₂-aryl where aryl is as defined above; R⁵ is H, R 4a is C₁-C₆-alkyl, aryl or -CH₂-aryl where aryl is as defined above; 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 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, C₃-C₁₀-alkenyl; (b) straight chain or branched C₁-C₉-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, C₃-C₇-cycloalkyl, halo (Cl, Br, I, F) -OH, -NH₂, -NH(C₁-C₄-alkyl), -CF₂CF₃, -N(C₁-C₄-alkyl)₂, -NH-SO₂R⁴, -COOR⁴, -CF₃, -CF₂CH₃, -SO₂NHR⁹; or (c) an unsubstituted, monosubstituted or disubstituted aromatic 5 or 6 membered cyclic 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) perfluoro-C₁-C₄-alkyl, (e) G3-G7-cycloalkyl optionally mono- or disubstituted with C₁-C₄-alkyl or -CF₃; R⁹ is H, C₁-C₅-alkyl, aryl or -CH₂-aryl where aryl is as defined above; R¹⁰ is H, C₁-C₄-alkyl; R¹¹ is H, C₁-C₆-alkyl, C₂-C₄-alkenyl, C₁-C₄-alkoxy-C₁-C₄-alkyl, or R¹² is -CN, -NO₂ or -CO₂R⁴; R¹³ is H, -CO(C₁-C₄-alkyl), 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; R¹⁷ is -NR⁹R¹⁰, -OR¹⁰, -NHCONH₂, -NHCSNH₂, 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; R²³ is (a) aryl as defined above, (b) heteroaryl as defined above, (c) C₃-C₄-cycloalkyl, (d) C₁-C₄-alkyl which can be optionally substituted with a substituent that is a member 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), -NHCOR 4a , -N(C₁-C₄-alkyl)₂, -PO₃H, -PO(OH)(C₁-C₄-alkyl), -PO(OH)(aryl) or -PO(OH) (O-C₁-C₄-alkyl), (e) perfluoro-C₁-C₄-alkyl; X is absent or 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-, Z is O, NR¹³ or S; -A-B-C-D- represents the constituent atoms of a 6-member saturated or unsaturated heterocyclic ring with the imidazole to which they are attached containing 1 to 3 nitrogen atoms and includes the following: wherein: R⁷ groups can be the same or different and represent: a) hydrogen, b) C₁-C₆ straight or branched chain alkyl, or C₂-C₆ alkenyl, or alkynyl each of which is unsubstituted or substituted with: i) -OH ii) C₁-C₄-alkoxy, iii) -CO₂R⁴, iv) -COR⁴, vi) -CON(R⁴)₂ viii) -N(R⁴)₂, ix) aryl as defined above, x) heterocyclic as defined in (p) below, xi) -S(O) x R²³, xii) tetrazol-5-yl, xiii) -CONHSO₂R²³, xiv) -SO₂NH-heteroaryl, xv) -SO₂NHCOR²³, xix) -PO(OR⁴)₂, xx) -PO(OR⁴)R⁹, c) halo, such as chloro, bromo or iodo, d) perfluoro-C₁-C₄-alkyl, e) -OH, f) -NH₂, i) -OR²³, j) -CO₂R⁴, k) -CON(R⁴)₂, l) -NH-C₃-C₇-cycloalkyl, m) C₃-C₇ cycloalkyl, n) aryl as defined above, or o) heterocyclic which is a five- or six-­membered saturated or unsaturated ring containing up to three heteroatoms selected from the group consisting of O, N or S wherein S may in the form of sulfoxide or sulfone and which may be optionally substituted with one or two substituents which are members selected from the group consisting of halo (Cl, Br, F, I), C₁-C₄-alkyl, C₁-C₄-alkoxy, C₁-C₄-S(O) x - where x is as defined above, CF₃, NO₂, OH, CO₂H, CO₂-C₁-C₄-alkyl, NH₂, NH(C₁-C₄-alkyl) or N(R⁴)₂; p) -CN, q) where n is 4 to 6, r) -SO₂N(R⁴)₂; s) tetrazol-5-yl, t) -CONHSO₂R²³, u) -PO(OR⁴)₂, v) -NHSO₂CF₃, w) -SO₂NH-heteroaryl, x) -SO₂NHCOR²³, y) -S(O) x -R²³, aa) -PO(OR⁴)R⁹, bb) -NHSO₂R²³, cc) -NHSO₂NHR²³, dd) -NHSO₂NHCOR²³, ee) NHCONHSO₂R²³, ff) -N(R⁴)CO₂R²³, hh) -CO-aryl, jj) -CO-C₁-C₄-alkyl, kk) -SO₂NH-CN, R⁸ groups can be the same or different and represent: a) hydrogen, b) C₁-C₆-alkyl or alkenyl either unsubstituted or substituted with hydroxy, C₁-C₄-alkoxy, -N(R⁴)₂, -CO₂R⁴ or C₃-C₅-cycloalkyl, c) C₃-C₅-cycloalkyl, R 8a is R⁸ or C₁-C₄-acyl; R 9a groups can be the same or different and represent: a) hydrogen, b) C₁-C₆ alkyl either unsubstituted or substituted with i) hydroxy, ii) -CO₂R⁴, iii) -CONHR⁴, or iv) -CON(R⁴)₂; and, the pharmaceutically acceptable salts thereof.