Substituted pyrimidinones as angiotensin II antagonists

Claim 1

A compound of formula (I): wherein: J is -C(=M)- or K is -C(=M)- or provided that one and only one of J and K is -C(=M)-; M is O or NR²¹; one of a and b is a double bond, provided that when J is -C(=M)- b is a double bond and when K is -C(=M)- a is a double bond; R¹ is (a) -CO₂R⁴, (b) -SO₃R⁵, (c) -NHSO₂CF₃, (d) -PO(OH⁵)₂, (e) -SO₂-NH-R⁹, (f) -CONHOR⁵, (h) -CN, (i) -PO(OR⁵)R⁴ (p) CONHSO₂R²¹; (q) SO₂NHCOR²¹; (r) -SO₂NH-heteroaryl, (s) -SO₂NHCONHR²¹, (t) -CH₂SO₂NH-heteroaryl, (u) -CH₂SO₂NHCO-R²¹, (v) -CH₂CONH-SO₂R²¹, (w) -NHSO₂NHCO-R²¹, (x) -NHCONHSO₂-R²¹, 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 each independently (a) H, (b) halogen, (c) NO₂, (d) NH₂, (e) C₁-C₄-alkylamino, (f) di(C₁-C₄-alkyl)amino (g) SO₂NHR⁹, (h) CF₃, (i) C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, or (j) 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, C₂-C₆-alkenyl, C₂-C₆-alkynyl, (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-alkylsulfinyl, (m) C₁-C₄-alkylsulfonyl, (n) NH₂, (o) C₁-C₄-alkylamino, (p) C₁-C₄-dialkylamino, (q) perfluoro-C₁-C₄-alkyl, (r) -SO₂-NHR⁹, (s) aryl or (t) furyl; wherein aryl is phenyl optionally substituted with one or two substituents selected from the group consisting of halo(Cl, Br, I, F) or C₁-C₄-alkyl optionally substituted with members selected from the group consisting of N(R⁴)₂, CO₂R⁴, OH, N(R⁴)CO₂R²¹, S(O) x R²¹ where x is 0 to 2; C₁-C₄-alkoxy, NO₂, CF₃, C₁-C₄-alkylthio, OH, NH₂, -NH(C₁-C₄-alkyl), -N(C₁-C₄-alkyl)₂, -CO₂H, -CO₂-C₁-C₄-alkyl, -N(R⁴)CO₂R²¹ or R⁴ is H, straight chain or branched C₁-C₆-alkyl optionally substituted with aryl as defined above; R 4a is C₁-C₆-alkyl, aryl or aryl-CH₂- wherein 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; (b) straight chain or branched C₁-C₆-alkyl, 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, CF₃, -CF₂CF₃, CCl₃, -NH₂, -NH(C₁-C₄-alkyl), -N(C₁-C₄-alkyl)₂, -NH-SO₂R⁴, -COOR⁴, -SO₂NHR⁹, C₁-C₄-alkoxy, C₁-C₄-alkyl-S; (c) an unsubstituted, monosubstituted or disubstituted heteroaromatic 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), NO₂, -CO₂H, -CO₂-C₁-C₄-alkyl, -NH₂, -NH(C₁-C₄-alkyl), -N(C₁-C₄-alkyl)₂; (d) C₃-C₇-cycloalkyl; R⁷ and R⁸ are independently (a) H, (b) aryl-C₁-C₄-alkyl-, (c) heteroaryl-C₁-C₄-alkyl-, (d) C₁-C₄-alkyl optionally substituted with a substituent selected from the group consisting of -OH, -NH₂, guanidino, C₁-C₄-alkoxy, -S(O) x R²¹, C₁-C₄-alkylamino, C₁-C₄-dialkylamino, -COOR⁴, -CON(R⁴)R²¹, -OCON(R⁴)R²¹, -O-COR⁴, C₃-C₅-cycloalkyl, -N(R⁴)CON(R⁴)R²¹, -N(R⁴)COOR²¹, -CONHSO₂R²¹, -N(R⁴)SO₂R²¹; (e) C₂-C₄-alkenyl, (f) -CO-aryl as defined above, (g) C₃-C₇-cycloalkyl, (h) halo (Cl, Br, I, F), (i) -OH, (j) -OR²¹, (k) perfluoro-C₁-C₄-alkyl, (l) -SH, (m) -S(O) x R²¹ where x is as defined above, (n) -CHO, (o) -CO₂R⁴, (p) -SO₃H, (q) -N(R⁴)₂, (r) -NHCO₂R²¹, (s) -SO₂NR⁹R¹⁰, (t) -CH₂OCOR⁴, (u) -N(R⁴)-SO₂-C₁-C₄-alkyl, (v) 5 or 6 membered saturated heterocycle containing one nitrogen atom and optionally containing one other heteroatom selected from N, O or S, such as pyrrolidine, morpholine, or piperazine, (w) aryl as defined above, (x) heteroaryl as defined above, (z) -NHSO₂-perfluoro-C₁-C₄-alkyl. (aa) -CONHSO₂R²¹, (bb) -SO₂NHCOR²¹, (cc) -SO₂NH-heteroaryl as defined above, (dd) -S(O) x -aryl as defined above, (ee) -S(O) x CH₂-aryl as defined above, (ff) -CON(R⁴)₂; R⁹ is H, C₁-C₅-alkyl, phenyl or benzyl; R¹⁰ is H, C₁-C₄-alkyl; R¹¹ is H, C₁-C₆-alkyl, C₂-C₄-alkenyl, C₁-C₄-alkoxy 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; 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; R²¹ is (a) aryl as defined above; (b) heteroaryl as defined above; (c) C₁-C₆-alkyl optionally substituted with a substituent selected from the group consisting of aryl as defined above, heteroaryl as defined above, -OH, -NH₂, -NH(C₁-C₄-alkyl), -N(C₁-C₄-alkyl)₂, -CO₂H, -CO₂R⁴, halo (Cl, Br, F, I), -CF₃; (d) C₃-C₅-cycloalkyl; 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-, r is 1 or 2; and the pharmaceutically acceptable salts thereof.