Patent ID: 6552019
Filing Date: 2003-04-22
Classification: A61P,C07D

Abstract:
A compound of the formula: wherein each of Q1 and Q2 are independently selected from a phenyl or 5-6 membered aromatic heterocyclic ring system, or an 8-14 membered saturated, partially unsaturated, or aromatic bicyclic or tricyclic ring system containing 0-4 heteroatoms;the rings that make up Q1 are substituted with 1 to 4 substituents, each of which is independently selected from halo; C1-C3 aliphatic optionally substituted with halo, Râ€², N(Râ€²)2, ORâ€², CO2Râ€² or CON(Râ€²)2; Oâ€”(C1-C3)-aliphatic optionally substituted with halo, Râ€², N(Râ€²)2, ORâ€², CO2Râ€² or CON(Râ€²)2; Râ€²; N(Râ€²)2; OCF3; CF3; NO2; CO2Râ€²; CON(Râ€²)2; SRâ€²; S(O2)N(Râ€²)2; SCF3; CN; N(Râ€²)C(O)R4; N(Râ€²)C(O)OR4; N(Râ€²)C(O)C(O)R4; N(Râ€²)S(O2)R4; N(Râ€²)R4; N(R4)2; OR4; OC(O)R4; OP(O)3H2; N&boxH;CRâ€²â€”N(Râ€²)2; SO2Râ€²; or C(O)Râ€²; the rings that make UP Q2 are optionally substituted with up to 4 substituents, each of which is independently selected from halo; C1-C3 aliphatic optionally substituted with halo, Râ€², N(Râ€²)2, ORâ€², CO2Râ€², S(O2)N(Râ€²)2, N&boxH;CRâ€²â€”N(Râ€²)2, R3, Oâ€”P(O3)H2, or CON(Râ€²)2; Oâ€”(C1-C3)-aliphatic optionally substituted with halo, Râ€², N(Râ€²)2, ORâ€², CO2Râ€², S(O2)N(Râ€²)2, N&boxH;CRâ€²â€”N(Râ€²)2, R3, OP(O3)H2, or CON(Râ€²)2; Râ€²; N(Râ€²)2; OCF3; CF3; NO2; CO2Râ€²; CON(Râ€²)2; R3; OR3; N(R3)2; SR3; C(O)R3; C(O)N(Râ€²)R3; C(O)OR3; SRâ€²; S(O2)N(Râ€²)2; SCF3; N&boxH;CRâ€²â€”N(Râ€²)2; R4; Oâ€”CO2R4; N(Râ€²)C(O)R4; N(Râ€²)C(O)OR4; N(Râ€²)C(O)C(O)R4; N(Râ€²)S(O2)R4; N(Râ€²)R4; N(R4)2; OR4; OC(O)R4; OP(O)3H2; or CN; each Râ€² is independently selected from hydrogen; (C1-C3)-aliphatic; phenyl or phenyl substituted with 1 to 3 substituents independently selected from halo, methoxy, cyano, nitro, amino, hydroxy, methyl or ethyl; or a 5-8 membered heterocyclic ring system optionally substituted with 1 to 3 substituents independently selected from halo, methoxy, cyano, nitro, amino, hydroxy, methyl or ethyl; each R3 is independently selected from a 5-8 membered aromatic or non-aromatic carbocyclic or heterocyclic ring system each optionally substituted with halo, Râ€², R4, â€”C(O)Râ€², â€”C(O)R4, â€”C(O)OR4, â€”J or â€”K; or an 8-10 membered saturated, partially unsaturated, or aromatic bicyclic ring system containing 0-4 heteroatoms, said ring system optionally substituted with halo, Râ€², R4, â€”C(O)Râ€², â€”C(O)R4, â€”C(O)OR4, â€”J or â€”K; each R4 is independently selected from â€”N(Râ€²)2; â€”NRâ€²C(O)â€”(C1-C4)-aliphatic optionally substituted with halo, Râ€², N(Râ€²)2, ORâ€², CO2Râ€², CON(Râ€²)2, SO2N(Râ€²)2, SO2N(R5)2, â€”J or â€”K; â€”NRâ€²â€”(C1-C4)-aliphatic optionally substituted with halo, Râ€², N(Râ€²)2, ORâ€², CO2Râ€², CON(Râ€²)2, SO2N(Râ€²)2, SO2N(R5)2, â€”J or â€”K; â€”OC(O)â€”N(Râ€²)2; a (C1-C4)-aliphatic, wherein up to two saturated carbon atoms of the aliphatic chain are each optionally and independently replaced by â€”C(O)â€”, â€”C(O)NRâ€²â€”, â€”C(O)NRâ€²NRâ€²â€”, â€”CO2â€”, â€”NRâ€²C(O)NRâ€²â€”, â€”OC(O)â€”, C(O)C(O)â€”, â€”OC(O)NRâ€²â€”, â€”NRâ€²NRâ€²â€”, â€”NRâ€²COâ€”, â€”NRâ€²Oâ€”, â€”Oâ€”, â€”Sâ€”, â€”SOâ€”, â€”SO2â€”, â€”NRâ€²â€”, â€”SO2NRâ€²â€”, â€”NRâ€²â€”SO2â€”, and wherein the aliphatic chain is optionally substituted with halo, Râ€², N(Râ€²)2, ORâ€², CO2Râ€², CON(Râ€²)2, SO2N(Râ€²)2, SO2N(R5)2, â€”J or â€”K; a (C1-C7)-aliphatic optionally substituted with halo, Râ€², N(Râ€²)2, ORâ€², CO2Râ€², CON(Râ€²)2, SO2N(Râ€²)2, SO2N(R5)2, â€”J or â€”K; â€”J; â€”K; or a 5-6 membered aromatic or non-aromatic carbocyclic or heterocyclic ring system optionally substituted with halo, Râ€², N(Râ€²)2, ORâ€², CO2Râ€², C(O)N(Râ€²)2, SO2N(Râ€²)2 SO2N(R5)2, â€”J or â€”K; R5 is selected from hydrogen; or a (C1-C3)-aliphatic optionally substituted with halo, â€”Râ€², â€”N(Râ€²)2, â€”ORâ€², SRâ€², â€”C(O)N(Râ€²)2, â€”S(O)2N(Râ€²)2, â€”C(O)ORâ€², â€”N(Râ€²)S(O)2(Râ€²), â€”N(Râ€²)SO2R6, â€”C(O)N(Râ€²)(R6), â€”N(Râ€²)C(O)Râ€², â€”N(Râ€²)(R6), â€”C(O)R6, â€”C(O)N&boxH;C(NHRâ€²)2 or R6; R6 is selected from 5-8 membered aromatic or non-aromatic carbocyclic or heterocyclic ring systems each optionally substituted with halo, Râ€², â€”C(O)Râ€² or â€”C(O)ORâ€²; or an 8-10 membered saturated, partially unsaturated, or aromatic ring system containing 0-4 heteroatoms, said ring system optionally substituted with halo, Râ€², â€”C(O)Râ€² or C(O)ORâ€²; Z is N, CH, C(OCH3), C(CH3), C(NH2), C(OH) or C(F); W is CH, C(OCH3), C(CH3), C(NH2), C(OH) or C(F); J is T or is a (C1-C4) aliphatic substituted with T; T is V, O(V) or NH(V); V is C(O)N&boxH;C(R)(N(R)2) wherein the two geminal R on the nitrogen are optionally taken together with the nitrogen to form a 4-8 membered heterocyclic ring; each R is independently selected from hydrogen, â€”R2, â€”N(R2)2, â€”OR2, SR2, â€”C(O)N(R2)2, â€”S(O2)N(R2)2, â€”C(O)OR2 or â€”C(O)R2 wherein two adjacent R are optionally bound to one another and, together with each C or N to which they are respectively bound, form a 4-8 membered carbocyclic or heterocyclic ring; R2 is selected from hydrogen; or a (C1-C3)-aliphatic optionally substituted with halo, â€”Râ€², â€”N(Râ€²)2, â€”ORâ€², SRâ€², â€”C(O)N(Râ€²)2, â€”S(O2)N(Râ€²)2, â€”C(O)ORâ€², â€”N(Râ€²)SO2R8, â€”N(Râ€²)SO2R7, â€”C(O)N(Râ€²)(R7), â€”N(Râ€²)C(O)R8, â€”N(Râ€²)(R7), â€”N(Râ€²)(R8), â€”C(O)R7, â€”C(O)N(Râ€²)(R8), â€”N(R8)2, â€”C(O)N&boxH;C(NHRâ€²)2 or R7; R7 is selected from 5-8 membered aromatic or non-aromatic carbocyclic or heterocyclic ring systems each optionally substituted with halo, Râ€², R8, â€”C(O)Râ€², â€”C(O)R8, â€”C(O)OR8; or an 8-10 membered saturated, partially unsaturated, or aromatic bicyclic ring system containing 0-4 heteroatoms, said ring system optionally substituted with halo, Râ€², R8, â€”C(O)Râ€², â€”C(O)R8, or â€”C(O)OR8; R8 is selected from (C1-C4)-aliphatic, wherein up to two saturated carbon atoms of the aliphatic chain are each optionally and independently replaced by â€”C(O)â€”, â€”C(O)NRâ€²â€”, â€”C(O)NRâ€²NRâ€²â€”, â€”CO2â€”, â€”NRâ€²C(O)NRâ€²â€”, â€”OC(O)â€”, â€”C(O)C(O)â€”, â€”OC(O)NRâ€²â€”, â€”NRâ€²NRâ€²â€”, â€”NRâ€²COâ€”, â€”NRâ€²Oâ€”, â€”Oâ€”, â€”Sâ€”, â€”SOâ€”, â€”SO2â€”, â€”NRâ€²â€”, â€”SO2NRâ€²â€”, â€”NRâ€²SO2â€”, and wherein the aliphatic chain is optionally substituted with halo, Râ€², N(Râ€²)2, ORâ€², CO2Râ€², CON(Râ€²)2, SO2N(Râ€²)2, SO2N(Râ€²)2; a (C1-C7)-aliphatic optionally substituted with halo, Râ€², N(Râ€²)2, ORâ€², CO2Râ€², CON(Râ€²)2, SO2N(Râ€²)2, SO2N(R5)2; or a 5-6 membered carbocyclic or heterocyclic ring system optionally substituted with halo, Râ€², N(Râ€²)2, ORâ€², CO2Râ€², C(O)N(Râ€²)2, SO2N(Râ€²)2, or SO2N(Râ€²)2; K is â€”C(O)â€”D, a (C1-C4) aliphatic substituted with D or â€”OP(O)(OH)2; D is M is either O or NH; G is selected from NH2, OH, or H; R9 is H; OH; C(O)OH; (C1-C7)-aliphatic optionally substituted with halo, Râ€², N(Râ€²)2, ORâ€², CO2Râ€², CON(Râ€²)2, or SO2N(Râ€²)2; or a 5-6 membered carbocyclic or heterocyclic ring system optionally substituted with halo, Râ€², N(Râ€²)2, ORâ€², CO2Râ€², C(O)N(Râ€²)2, or SO2N(Râ€²)2; or G and R9 taken together with the intervening carbon may form a ring.