Patent ID: 6284764
Filing Date: 2001-09-04
Classification: A61P,C07D

Abstract:
A compound of the formula 1 ##STR15##or a pharmaceutically acceptable salt or solvate thereof, wherein:X is N;A represents a fused 6-membered carbon 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 said A moiety is optionally substituted with 1 to 3 R.sup.5 groups;each R.sup.1 and R.sup.2 is independently H or C.sub.1 -C.sub.6 alkyl;R.sup.3 is --(CR.sup.1 R.sup.2).sub.m --R.sup.8 wherein m is 0 or 1;or R.sup.1 and R.sup.3 are taken together to form a group of the formula ##STR16##wherein said group is optionally substituted with 1 to 3 R5 groups;R.sup.4 is --(CR.sup.1 R.sup.2).sub.m --C.ident.C--(CR.sup.1 R.sup.2).sub.t R.sup.9, --(CR.sup.1 R.sup.2).sub.m --C.dbd.C--(CR.sup.1 R.sup.2).sub.t --R.sup.9, --C.dbd.NOR.sup.12, or --X.sup.1 --R.sup.12 wherein m is an integer from 0 to 3, t is an integer from 0 to 5, and X.sup.1 is a divalent group derived from azetidine, oxetane or a C.sub.3 -C.sub.4 carbocyclic group;or R.sup.4 is --(CR.sup.1 R.sup.2).sub.m --C.ident.C--(CR.sup.1 R.sup.2).sub.k R.sup.13 or --(CR.sup.1 R.sup.2).sub.m --C.dbd.C--(CR.sup.1 R.sup.2).sub.k R.sup.13 wherein k is an integer from 1 to 3 and m is an integer from 0 to 3;or R.sup.4 is --(CR.sup.1 R.sup.2).sub.t R.sup.9, wherein t is an integer from 0 to 5 and the attachment point to R.sup.9 is through a carbon atom of the R.sup.9 group;each R.sup.5 is independently selected from halo, hydroxy, --NR.sup.1 R.sup.2, C.sub.1 -C.sub.6 alkyl, trifluoromethyl, C.sub.1 -C.sub.6 alkoxy, trifluoromethoxy, --C(O)R.sup.6, --CO.sub.2 R.sup.6, --NR.sup.6 C(O)R.sup.1, --C(O)NR.sup.6 R.sup.7, --SO.sub.2 NR.sup.6 R.sup.7, --NR.sup.6 C(O)NR.sup.7 R.sup.1, and --NR.sup.6 C(O)OR.sup.7 ;each R.sup.6 and R.sup.7 is independently selected from H, C.sub.1 -C.sub.6 alkyl, --(CR.sup.1 R.sup.2).sub.t (C.sub.6 -C.sub.10 aryl), and --(CR.sup.1 R.sup.2).sub.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 (.dbd.O) moiety, and the alkyl, aryl and heterocyclic moieties of the foregoing R.sup.6 and R.sup.7 groups are optionally substituted with 1 to 3 substituents independently selected from halo, cyano, nitro, --NR.sup.1 R.sup.2, trifluoromethyl, trifluoromethoxy, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl, hydroxy, and C.sub.1 -C.sub.6 alkoxy;R.sup.8 is independently selected from --(CR.sup.1 R.sup.2).sub.t (C.sub.6 -C.sub.10 aryl) and --(CR.sup.1 R.sup.2).sub.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 (.dbd.O) moiety, and each of the foregoing R.sup.8 groups is optionally substituted with 1 to 5 R.sup.10 groups;R.sup.9 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).sub.j wherein j is an integer from 0 to 2, and --NR.sup.12, provided that two O atoms, two S(O).sub.j moieties, an O atom and a S(O).sub.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 R.sup.11 groups;each R.sup.10 is independently selected from halo, cyano, nitro, trifluoromethoxy, trifluoromethyl, azido, hydroxy, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl, --C(O)R.sup.6, --C(O)OR.sup.6, --OC(O)R.sup.6, --NR.sup.6 C(O)R.sup.7, --NR.sup.6 C(O)NR.sup.1 R.sup.7, --NR.sup.6 C(O)OR.sup.7, --C(O)NR.sup.6 R.sup.7, --NR.sup.6 R.sup.7, --NR.sup.6 OR.sup.7, --SO.sub.2 NR.sup.6 R.sup.7, --S(O).sub.j (C.sub.1 -C.sub.6 alkyl) wherein j is an integer from 0 to 2, --(CR.sup.1 R.sup.2).sub.t (C.sub.6 -C.sub.10 aryl), --(CR.sup.1 R.sup.2).sub.t (4-10 membered heterocyclic), --(CR.sup.1 R.sup.2).sub.q C(O)(CR.sup.1 R.sup.2).sub.t (C.sub.6 -C.sub.10 aryl), --(CR.sup.1 R.sup.2).sub.q C(O)(CR.sup.1 R.sup.2).sub.t (4-10 membered heterocyclic), --(CR.sup.1 R.sup.2).sub.t O(CR.sup.1 R.sup.2).sub.q (C.sub.6 -C.sub.10 aryl), --(CR.sup.1 R.sup.2).sub.t O(CR.sup.1 R.sup.2).sub.q (4-10 membered heterocyclic), --(CR.sup.1 R.sup.2).sub.q S(O).sub.j (CR.sup.1 R.sup.2).sub.t (C.sub.6 -C.sub.10 aryl), and --(CR.sup.1 R.sup.2).sub.q S(O).sub.j (CR.sup.1 R.sup.2).sub.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 R.sup.10 groups are optionally substituted with an oxo (.dbd.O) moiety, and the alkyl, alkenyl, alkynyl, aryl and heterocyclic moieties of the foregoing R.sup.10 groups are optionally substituted with 1 to 3 substituents independently selected from halo, cyano, nitro, trifluoromethyl, trifluoromethoxy, azido, --OR.sup.6, --C(O)R.sup.6, --C(O)OR.sup.6, --OC(O)R.sup.6, --NR.sup.6 C(O)R.sup.7, --C(O)NR.sup.6 R.sup.7, --NR.sup.6 R.sup.7, --NR.sup.6 OR.sup.7, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl, --(CR.sup.1 R.sup.2).sub.t (C.sub.6 -C.sub.10 aryl), and --(CR.sup.1 R.sup.2).sub.t (4-10 membered heterocyclic), wherein t is an integer from 0 to 5;each R.sup.11 is independently selected from --R.sup.12, --OR.sup.1, --NR.sup.1 R.sup.2, --NR.sup.6 C(O)R.sup.7, --NR.sup.6 C(O)NR.sup.7 R.sup.1, --NR.sup.6 C(O)OR.sup.7, and --NR.sup.6 SO.sub.2 NR.sup.7 R.sup.1, or R.sup.11 replaces two hydrogen atoms on a carbon to form an oxo (C.dbd.O) group;R.sup.12 is R.sup.6, --C(O)R.sup.6 or --SO.sub.2 R.sup.6, --C(O)NR.sup.6 R.sup.7, --SO.sub.2 NR.sup.6 R.sup.7, or --CO.sub.2 R.sup.6 ;R.sup.13 is --NR.sup.1 R.sup.12 or --OR.sup.12 ;and wherein any of the above-mentioned substituents comprising a CH.sub.3 (methyl), CH.sub.2 (methylene), or CH (methine) group which is not attached to a halogeno, SO or SO.sub.2 group or to a N, O or S atom optionally bears on said group a substituent selected from hydroxy, halo, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy and --NR.sup.1 R.sup.2.