Patent ID: 6699893
Filing Date: 2004-03-02
Classification: A61P,C07C,C07D

Abstract:
A compound of formula I an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug; wherein m is 1 or 2;â€” represents an optional bond; A is G, H and I together with 2 carbon atoms from the A-ring or 2 carbon atoms from the B-ring form a 5-membered heterocyclic ring comprising one or more N, O or S atoms; provided that there is at most one of O and S per ring; J, K, L and M together with 2 carbon atoms from the B-ring forms a 6-membered heterocyclic ring comprising 1 or more N atoms; X is a) absent, b) â€”CH2â€”, c) â€”CH(OH)â€” or d) â€”C(O)â€”; R1 is a) â€”H, b) â€”Zâ€”CF3, c) â€”(C1-C6)alkyl, d) â€”(C2-C6)alkenyl, e) â€”(C2-C6)alkynyl, f) â€”CHO, g) â€”CH&boxH;Nâ€”OR12, h) â€”Zâ€”C(O)OR12, i) â€”Zâ€”C(O)â€”NR12R13, j) â€”Zâ€”C(O)â€”R12â€”Z-het, k) â€”Zâ€”NR12R13, l) â€”Zâ€”NR12het, m) â€”Z-het, n) â€”Zâ€”O-het, o) â€”Z-arylâ€², p) â€”Zâ€”O-arylâ€², q) â€”CHOH-arylâ€² or r) â€”C(O)-arylâ€² wherein arylâ€² in substituents o) to r) is substituted independently with 0, 1 or 2 of the following: â€”Zâ€”OH, â€”Zâ€”NR12R13, â€”Zâ€”NR12-het, â€”C(O)NR12R13, â€”C(O)O(C1-C6)alkyl, â€”C(O)OH, â€”C(O)-het, â€”NR12â€”C(O)â€”(C1-C6)alkyl, â€”NR12â€”C(O)â€”(C2-C6)alkenyl, â€”NR12â€”C(O)â€”(C2-C6)alkynyl, â€”NR12â€”C(O)â€”Z-het, â€”CN, â€”Z-het, â€”Oâ€”(C1-C3)alkyl- C(O)â€”NR12R13, â€”NR12â€”Zâ€”C(O)â€”NR12R13, â€”Zâ€”N R12â€”SO2â€”R13, â€”NR12â€”SO2-het, â€”C(O)H, â€”Zâ€”N 12â€”Zâ€”C(C1-C6)alkyl, â€”Zâ€”N R12â€”Zâ€”N R12R13, â€”Zâ€”NR12â€”(C3-C6)cycloalkyl, â€”Zâ€”N(Zâ€”O(C1-C6)alkyl)2, â€”O2R12, â€”SOR12, â€”SR12, â€”SO2N R12R13, â€”Oâ€”C(O)â€”(C1-C4)alkyl, â€”Oâ€”SO2â€”(C1-C4)alkyl, -halo or â€”CF3; Z for each occurrence is independently a) â€”(C1-C6)alkyl, b) â€”(C2C6)alkenyl or c) â€”(C2-C6)alkynyl; R2 is â€”OH; R3 is a) â€”H, b) â€”(C1-C10)alkyl wherein 1 or 2 carbon atoms, other than the connecting carbon atom, may optionally be replaced with 1 or 2 heteroatoms independently selected from S, O and N and wherein each carbon atom is substituted with 0, 1 or 2 Ry, c) â€”(C2-C10)alkenyl substituted with 0, 1 or 2 Ry, d) â€”(C2-C10)alkynyl wherein 1 carbon atom, other than the connecting carbon atom, may optionally be replaced with 1 oxygen atom and wherein each carbon atom is substituted with 0, 1 or 2 Ry, e) â€”CH&boxH;C&boxH;C2, f) â€”CN, g) â€”(C3-C6)cycloalkyl, h) â€”Z-aryl, i) â€”Z-het, j) â€”C(O)O(C1C6)alkyl, k) â€”O(C1-C6)alkyl, l) â€”Zâ€”Sâ€”R12, m) â€”Zâ€”S(O)â€”R12, n) â€”Zâ€”S(O)2â€”R12, o) â€”CF3 p) â€”NR12Oâ€”(C1-C6)alkyl or q) â€”CH2ORy; provided that one of R2 and R3 is absent when there is a double bond between CR2R3 (the 7 position) and the F moiety (the 8 position) of the C-ring; Ry for each occurrence is independently a) â€”OH, b) -halo, c) â€”Zâ€”CF3, d) â€”Zâ€”CF(C1-C3 alkyl)2, e) â€”CN, f) â€”NR12R13, g) â€”(C3-C6)cycloalkyl, h) â€”(C3-C6)cycloalkenyl, i) â€”(C0-C3)alkyl-aryl, j) -het or k) â€”N3; R4 and R5 for each occurrence are independently a) â€”H, b) â€”CN, â€”(C1-C6)alkyl substituted with 0 to 3 halo, d) â€”(C2-C6)alkenyl substituted with 0 to 3 halo, e) â€”(C2-C6)alkynyl substituted with 0 to 3 halo, f) â€”Oâ€”(C1-C6)alkyl substituted with 0 to 3 halo, g) â€”Oâ€”(C2-C6)alkenyl substituted with 0 to 3 halo, h) â€”Oâ€”(C2â€”C6)alkynyl substituted with 0 to 3 halo, i) halo, j) â€”OH, k) (C3-C6)cycloalkyl or l) (C3-C6)cycloalkenyl; or R4 and R5 are taken together to form &boxH;O; R6 is a) â€”H, b) â€”CN, c) â€”(C1-C6)alkyl substituted with 0 to 3 halo, d) â€”(C2-C6)alkenyl substituted with 0 to 3 halo, e) â€”(C2-06)alkynyl substituted with 0 to 3 hal or f) â€”OH; R7 and R16 for each occurrence are independently a) â€”H, b) -halo, c) â€”CN, d) â€”(C1-C6)alkyl substituted with 0 to 3 halo, e) â€”(C2-C6)alkenyl substituted with 0 to 3 halo or f) â€”(C2-C6)alkynyl substituted with 0 to 3 halo; provided that R7 is other than â€”CN or -halo when D is NR7; or R7 and R16 are taken together to form &boxH;O; R8, R9, R14 and R15 for each occurrence are independently a) â€”H b) -halo, c) (C1-C6)alkyl substituted with 0 to 3 halo, d) â€”(C2-C6)alkenyl substituted with 0 to 3 halo, e) â€”(C2-C6)alkynyl substituted with 0 to 3 halo, f) â€”CN, g) â€”(C3-C6)cycloalkyl, h) â€”(C3-C6)cycloalkenyl, i) â€”OH, j) â€”Oâ€”(C1-C6)alkyl, k) â€”Oâ€”(C1-C6)alkenyl, l) â€”Oâ€”(C1-C6)alkynyl, m) â€”NR12R13, n) â€”C(O)OR12 or o) â€”C(O)NR12R13; or R8 and R9 are taken together on the C-ring to form &boxH;O; provided that when m is 2, only one set of R8 and R9 are taken together to form &boxH;O; or R14 and R15 are taken together to form &boxH;O; provided that when R14 and R15 are taken together to form &boxH;O, D is other than CR7 and E is other than C; R10 is a) â€”(C1-C10)alkyl substituted with 0 to 3 substituents independently selected from -halo, â€”OH and â€”N3, b) â€”(C2-C10)alkenyl substituted with 0 to 3 substituents independently selected from -halo, â€”OH and â€”N3, c) â€”(C2-C10)alkynyl substituted with 0 to 3 substituents independently selected from -halo, â€”OH and â€”N3, d) -halo, e) â€”Zâ€”CN, f) â€”OH, g) â€”Z-het, h) â€”Zâ€”NR12R13, i) â€”Zâ€”C(O)-het, j) â€”Zâ€”C(O)â€”(C1-C6)alkyl, k) â€”Zâ€”C(O)â€”R12R13, l) â€”Zâ€”C(O)â€”NR12â€”Zâ€”CN, m) â€”Zâ€”C(O)â€”NR12â€”Z-het, n) â€”Zâ€”C(O)â€”NR12â€”Z-aryl, o) â€”Zâ€”C(O)â€”NR12â€”Zâ€”NR12R13, p) â€”Zâ€”C(O)â€”NR12â€”Zâ€”O(C1-C6)alkyl, q) â€”(C0-C6)alkyl- O(O)OH, r) â€”Zâ€”C(O)O(C1-C6)alkyl, s) â€”Zâ€”Oâ€”(C0-C6)alkyl-het, t) â€”Zâ€”Oâ€”(C0C6)alkyl-aryl, u) â€”Zâ€”Oâ€”(C1-C6)alkyl substituted with 0 to 2 Rx, v) â€”Zâ€”Oâ€”(C1-C6)alkyl- OH(O), w) â€”Zâ€”Oâ€”(C1-C6)alkyl- NR12-het, x) â€”Zâ€”Oâ€”Z-het-Z-het, y) â€”Zâ€”Oâ€”Z-het-Zâ€”NR12R13, z) â€”Zâ€”Oâ€”Z-het-O(O)-het, a1) Zâ€”Oâ€”Zâ€”C(O)-het, b1) â€”Zâ€”Oâ€”Zâ€”C(O)-het-het, c1) â€”Zâ€”Oâ€”Zâ€”C(O)â€”(C1-C6)alkyl, d1) â€”Zâ€”Oâ€”Zâ€”O(S)â€”NR 2R13, e1) â€”Zâ€”Oâ€”Zâ€”C(O)â€”NR12R13, f1) â€”Zâ€”Oâ€”Z-(C1-C3)alkyl-O(O)â€”NR12R13, g 1) â€”Zâ€”Oâ€”Zâ€”CO(O)â€”O(C1-C6)alkyl, h1) â€”Zâ€”Oâ€”Zâ€”C(O)â€”OH, ii) â€”Zâ€”Oâ€”Zâ€”C(O)â€”NR12â€”O(C1-C6)alkyl, j1) â€”Zâ€”Oâ€”Zâ€”C(O)â€”NR12â€”OH, k1) â€”Zâ€”Oâ€”Zâ€”C(O)â€”NR12â€”Zâ€”NR12R13, 11) â€”Zâ€”Oâ€”Zâ€”C(O)â€”NR12â€”Z-het, m1) â€”Zâ€”Oâ€”Zâ€”C(O)â€”NR12â€”SO2â€”(C1-C6)alkyl, n1) â€”Zâ€”Oâ€”Zâ€”C(&boxH;N R12)(NR12R13), o1) â€”Zâ€”Oâ€”Zâ€”C(&boxH;NOR12)(NR12R13), p1) â€”Zâ€”NR12â€”C(O)â€”Oâ€”Zâ€”NR12R13, q1) â€”Zâ€”Sâ€”C(O)â€”NR12R13, r1) â€”Zâ€”Oâ€”SO2â€”(C1-C6)alkyl, s1) â€”Zâ€”Oâ€”SO2-aryl, t1) â€”Zâ€”Oâ€”SO2â€”NR12R13, u1) â€”Zâ€”SO2â€”CF3, v1) â€”Zâ€”NR12C(O)OR13 or w1) â€”Zâ€”NR12C(O)R13; or R9 and R10 are taken together on the moiety of formula A-5 to form a)&boxH;O or b)&boxH;NOR12, R11 is a) â€”H, b) â€”(C1-C5)alkyl, c) â€”(C3-C6)cycloalkyl or d) â€”(C0-C3)alkyl-aryl; R12 and R13 for each occurrence are each independently a) â€”H, b) â€”(C1-C6)alkyl wherein 1 or 2 carbon atoms, other than the connecting carbon atom, may optionally be replaced with 1 or 2 heteroatoms independently selected from S, O and N and wherein each carbon atom is substituted with 0 to 6 halo, c) â€”(C2-C6)alkenyl substitute with 0 to 6 halo or d) â€”(C1-C6)alkynyl wherein 1 carbon atom, other than the connecting carbon atom, may optionally be replaced with 1 oxygen atom and wherein each carbon atom is substituted with 0 to 6 halo; or R12 and R13 are taken together with N to form het; or R6 and R14 or R15 are taken together to form 1,3-dioxolanyl; aryl is a) phenyl substituted with 0 to 3 Rx, b) naphthyl substitute with 0 to 3 Rx or c) biphenyl substituted with 0 to 3 Rx; het is a 5-,6- or 7-membered saturated, partially saturated or unsaturated ring containing from one (1) to three (3) heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur; and including any bicyclic group in which any of the above heterocyclic rings is fused to a benzene ring or another heterocycle; and the nitrogen may be in the oxidized state giving the N-oxide form; and substituted with 0 to 3 Rx; Rx for each occurrence is independently a) -halo, b) â€”OH, c) â€”(C1-C6)alkyl, d) â€”(C2-C6)alkenyl, e) â€”(C2-C6)alkynyl, f) â€”O(C1-C6)alkyl, g) â€”O(C2-C6)alkenyl h) â€”O(C2-C6)alkynyl, i) â€”(C0-C6)alkyl-NR12R13, j) â€”C(O)â€”NR12R13, k) â€”Zâ€”SO2R12, l)â€”Zâ€”SO2R12, m) Zâ€”SR12, n) â€”NR12â€”SO2R13, o) â€”NR12â€”C(O)â€”R13, p) â€”NR12â€”OR13, q) â€”SO2â€”NR12R13, r) â€”CN, s) â€”CF3, t) â€”C(O)(C1-C6)alkyl, u) &boxH;O, v) â€”Zâ€”SO2-phenyl or w) â€”Zâ€”SO2-hetâ€²; arylâ€² is phenyl, naphthyl or biphenyl; hetâ€² is a 5-, 6- or 7-membered saturated, partially saturated or unsaturated ring containing from one (1) to three (3) heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur; and including any bicyclic group in which any of the above heterocyclic rings is fused to a benzene ring or another heterocycle; provided that: 1) Xâ€”R1 is other than hydrogen or methyl; 2) when R9 and R10 are substituents on the A-ring, they are other than mono- or di-methoxy; 5) when Xâ€”R1 is (C1-C4)alkyl, (C2-C4)alkenyl or (C2-C4)alkynyl, R9 and R10 are other than mono-hydroxy or &boxH;O, including the diol form thereof, when taken together; and 6) when X is absent, R1 is other than a moiety containing a heteroatom independently selected from N, O or S directly attached to the juncture of the B-ring and the C-ring.