Patent ID: 6541481
Filing Date: 2003-04-01
Classification: A61P,C07D

Abstract:
(Amended) A compound of the formula 1 or a pharmaceutically acceptable salt or solvate thereof wherein:X is N; A represents a fused 5-membered ring containing 1 heteroatom selected from â€”N(R1)â€”, O, and S(O)j, wherein j is an integer from 0 to 2, the fused ring containing a total of 1 or 2 double bonds inclusive of the bond in the pyrimidine ring to which it is fused wherein the R1 group attached to the nitrogen is absent if a double bond includes the foregoing optional nitrogen moiety â€”N(R1)â€” and wherein the carbon atoms of the A moiety are optionally substituted with 1 to 3 R5 groups; each R1 and R2 is independently H or C1-C6 alkyl; R3 is â€”(CR1R2)mâ€”R8 wherein m is 0 or 1; or R1 and R3 are taken together to form a group of the formula â€ƒwherein said group is optionally substituted with 1 to 3 R5 groups; R4 is â€”(CR1R2)mâ€”Câ‰¡Câ€”(CR1R2)tR9, â€”(CR1R2)mâ€”C&boxH;Câ€”(CR1R2)tâ€”R9, â€”C&boxH;NOR12, or â€”X1â€”R12 wherein m is an integer from 0 to 3, t is an integer from 0 to 5, and X1 is a divalent group derived from azetidine, oxetane or a C3-C4 carbocyclic group; or R4 is â€”(CR1R2)mâ€”Câ‰¡Câ€”(CR1R2)kR13 or â€”(CR1R2)mâ€”C&boxH;Câ€”(CR1R2)kR13 wherein k is an integer from 1 to 3 and m is an integer from 0 to 3; or R4 is â€”(CR1R2)tR9, wherein t is an integer from 0 to 5 and the attachment point to R9 is through a carbon atom of the R9 group; each R5 is independently selected from halo, hydroxy, â€”NR1R2, C1-C6 alkyl, trifluoromethyl, C1-C6 alkoxy, trifluoromethoxy, â€”C(O)R6, â€”CO2R6, â€”NR6C(O)R1, â€”C(O)NR6R7, â€”SO2NR6R7, â€”NR6C(O)NR7R1, and â€”NR6C(O)OR7; each R6 and R7 is independently selected from H, C1â€”C6 alkyl, â€”(CR1R2)t(C6â€”C10 aryl), and â€”(CR1R2)t(4-10 membered heterocyclic), wherein t is an integer from 0 to 5, 1 or 2 ring carbon atoms of the heterocyclic group are optionally substituted with an oxo (&boxH;O) moiety, and the alkyl, aryl and heterocyclic moieties of the foregoing R6 and R7 groups are optionally substituted with 1 to 3 substituents independently selected from halo, cyano, nitro, â€”NR1R2, trifluoromethyl, trifluoromethoxy, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, hydroxy, and C1-C6 alkoxy; R8 is independently selected from â€”(CR1R2)t(C6-C10 aryl) and â€”(CR1R2)k(4-10 membered heterocyclic), wherein t is an integer from 0 to 5, 1 or 2 ring carbon atoms of the heterocyclic group are optionally substituted with an oxo (&boxH;O) moiety, and each of the foregoing R8 groups is optionally substituted with 1 to 5 R10 groups; R9 is a non-aromatic mono-cyclic ring, a fused or bridged bicyclic ring, or a spirocyclic ring, wherein said ring contains from 3 to 12 carbon atoms in which from 0 to 3 carbon atoms are optionally replaced with a hetero moiety independently selected from N, O, S(O)j wherein j is an integer from 0 to 2, and â€”NR12â€”, provided that two O atoms, two S(O)j moieties, an O atom and a S(O)j moiety, an N atom and an S atom, or an N atom and an O atom are not attached directly to each other within said ring, and wherein the carbon atoms of said ring are optionally substituted with 1 to 2 R11 groups; each R10 is independently selected from halo, cyano, nitro, trifluoromethoxy, trifluoromethyl, azido, hydroxy, C1-C6 alkoxy, C1-C10 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, â€”C(O)R6, â€”C(O)OR6, â€”OC(O)R6, â€”NR6C(O)R7, â€”NR6C(O)NR1R7, â€”NR6C(O)OR7, â€”C(O)NR6R7, â€”NR6R7, â€”NR6OR7, â€”SO2NR6R7, â€”S(O)j(C1-C6 alkyl) wherein j is an integer from 0 to 2, â€”(CR1R2)t(C6-C10 aryl), â€”(CR1R2)t(4-10 membered heterocyclic), â€”(CR1R2)qC(O)(CR1R2)t(C6-C10 aryl), â€”(CR1R2)qC(O)(CR1R2)t(4-10 membered heterocyclic), â€”(CR1R2)tO(CR1R2)q(C6-C10 aryl), â€”(CR1R2)tO(CR1R2)q(4-10 membered heterocyclic), â€”(CR1R2)qS(O)j(CR1R2)t(C6-C10 aryl), and â€”(CR1R2)qS(O)j(CR1R2)t(4-10 membered heterocyclic), wherein j is 0, 1 or 2, q and t are each independently an integer from 0 to 5, 1 or 2 ring carbon atoms of the heterocyclic moieties of the foregoing R10 groups are optionally substituted with an oxo (&boxH;O) moiety, and the alkyl, alkenyl, alkynyl, aryl and heterocyclic moieties of the foregoing R10 groups are optionally substituted with 1 to 3 substituents independently selected from halo, cyano, nitro, trifluoromethyl, trifluoromethoxy, azido, â€”OR6, â€”C(O)R6, â€”C(O)OR6, â€”OC(O)R6, â€”NR6C(O)R7, â€”C(O)NR6R7, â€”NR6R7, â€”NR6OR7, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, â€”(CR1R2)t(C6-C10 aryl), and â€”(CR1R2)t(4-10 membered heterocyclic), wherein t is an integer from 0 to 5; each R11 is independently selected from â€”R12, â€”OR1, â€”NR1R2, â€”NR6C(O)R7, â€”NR6C(O)NR7R1, â€”NR6C(O)OR7, and â€”NR6SO2NR7R1, or R11 replaces two hydrogen atoms on a carbon to form an oxo (C&boxH;O) group; R12 is R6, â€”C(O)R6 or â€”SO2R6, â€”C(O)NR6R7, â€”SO2NR6R7, or â€”CO2R6; R13 is â€”NR1R12 or â€”OR12; and wherein any of the above-mentioned substituents comprising a CH3 (methyl), CH2 (methylene), or CH (methine) group which is not attached to a halogeno, SO or SO2 group or to a N, O or S atom optionally bears on said group a substituent selected from hydroxy, halo, C1-C4 alkyl, C1-C4 alkoxy and â€”NR1R2.