Patent ID: 6465449
Filing Date: 2002-10-15
Classification: A61K,A61P,C07D

Abstract:
A compound of the formula 1or a pharmaceutically acceptable salt or solvate thereof, wherein: X is N; A represents a fused 6-membered ring, the fused ring containing a total of 3 double bonds inclusive of the bond in the pyrimidine ring to which it is fused and wherein the carbon atoms of the A moiety are optionally substituted by 1 to 3 R5 groups; each R1 and R2 is independently H or C1-C6 alkyl; R3 is â€”(CR1R2)m-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)t(C6-C10 aryl) or â€”(CR1R2)t(4-10 membered heterocyclic), wherein t is an integer from 0 to 5, wherein said R4 groups are substituted with 1 to 3 groups independently selected from â€”(CR1R2)qNR1R9, â€”(CR1R2)qNR9(C1-C6 alkanoyl), â€”(CR1R2)qO(CR1R2)rR9, and â€”(CR1R2)qR9 wherein q and r are each independently an integer from 0 to 5, and wherein the heterocyclic, aryl and alkyl moieties of the foregoing groups are optionally substituted with 1 to 3 R10 groups; each R5 is independently selected from halo, hydroxy, â€”NR1R2, C1-C6 alkyl, trifluoromethyl, C1-C6 alkoxy, and trifluoromethoxy; each R6 and R7 is independently selected from H, C1-C6 alkyl, â€”(CR1R2)t(C6-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; each R8 is independently selected from â€”(CR1R2)t(C6-C1 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 each of the foregoing R8 groups is optionally substituted with 1 to 5 R10 groups; R9 is a fused or bridged bicyclic ring or a spirocyclic ring, wherein said ring contains from 5 to 12 carbon atoms in which up to 2 carbon atoms are optionally replaced with a hetero moiety selected from O, S(O)j wherein j is an integer from 0 to 2, and â€”NR11â€”, 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, and wherein said ring is saturated or partially unsaturated with up to two carbon-carbon double bonds, and the carbon atoms of said ring are optionally substituted with 1 to 4 R10 groups; or where R9 is as â€”NR1R9 then R9 optionally can be taken together with R1 and the nitrogen to which R1 and R9 are attached to form a fused or bridged bicyclic ring or a spirocyclic ring, wherein said ring is saturated and contains from 5 to 12 carbon atoms in which up to 2 carbon atoms are optionally replaced with a hetero moiety selected from O, S(O)j wherein j is an integer from 0 to 2, and â€”NR1â€”, provided that two O atoms, two S(O)j moieties, or an O atom and a S(O)j moiety are not attached directly to each other, and wherein the carbon atoms of said rings are optionally substituted with 1 to 4 R10 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)R5, â€”C(O)OR6, â€”OC(O)R6, â€”NR6C(O)R7, 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)qSO2(CR1R2)t(C6-C10 aryl), and â€”(CR1R2)qSO2(CR1R2)t(4-10 membered heterocyclic), wherein 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; R11 is H, C1-C6 alkyl, â€”C(O)R6 or â€”SO2R6; 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.