Substituted bicyclic derivatives useful as anticancer agents

A compound of the formula 1

• 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 R5 groups;
• each R1 and R2 is independently H or C1-C6 alkyl;
• R3 is —(CR1R2)m—R8 wherein m is 0 or 1;
• or R1 and R3 are taken together to form a group of the formula
• wherein said group is optionally substituted with 1 to 3 R5 groups;
• R4 is —(CR1R2)m—C≡C—(CR1R2)tR9, —(CR1R2)m—C═C—(CR1R2)t—R9, —C═NOR12, or —X1—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 —(CR1R2)m—C≡C—(CR1R2)kR13 or —(CR1R2)m—C═C—(CR1R2)kR13 wherein k is an integer from 1 to 3 and m is an integer from 0 to 3;
• or R4 is —(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, —NR1R2, C1-C6 alkyl, trifluoromethyl, C1-C6 alkoxy, trifluoromethoxy, —C(O)R6, —CO2R6, —NR6C(O)R1, —C(O)NR6R7, —SO2NR6R7, —NR6C(O)NR7R1, and —NR6C(O)OR7;
• each R6 and R7 is independently selected from H, C1-C6 alkyl, —(CR1R2)t(C6-C10 aryl), and —(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 (═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, —NR1R2, trifluoromethyl, trifluoromethoxy, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, hydroxy, and C1-C6 alkoxy;
• R8 is independently selected from —(CR1R2)t(C6-C10 aryl) and —(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 (═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 —NR12, 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, —C(O)R6, —C(O)OR6, —OC(O)R6, —NR6C(O)R7, —NR6C(O)NR1R7, —NR6C(O)OR7, —C(O)NR6R7, —NR6R7, —NR6OR7, —SO2NR6R7, —S(O)j(C1-C6 alkyl) wherein j is an integer from 0 to 2, —(CR1R2)t(C6-C10 aryl), —(CR1R2)t(4-10 membered heterocyclic), —(CR1R2)qC(O)(CR1R2)t(C6-C10 aryl), —(CR1R2)qC(O)(CR1R2)t(4-10 membered heterocyclic), —(CR1R2)tO(CR1R2)q(C6-C10 aryl), —(CR1R2)tO(CR1R2)q(4-10 membered heterocyclic), —(CR1R2)qS(O)j(CR1R2)t(C6-C10 aryl), and —(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 (═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, —OR6, —C(O)R6, —C(O)OR6, —OC(O)R6, —NR6C(O)R7, —C(O)NR6R7, —NR6R7, —NR6OR7, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, —(CR1R2)t(C6-C10 aryl), and —(CR1R2)t(4-10 membered heterocyclic), wherein t is an integer from 0 to 5;
• each R11 is independently selected from —R12, —OR1, —NR1R2, —NR6C(O)R7, —NR6C(O)NR7R1, —NR6C(O)OR7, and —NR6SO2NR7R1, or R11 replaces two hydrogen atoms on a carbon to form an oxo (C═O) group;
• R12 is R6, —C(O)R6 or —SO2R6, —C(O)NR6R7, —SO2NR6R7, or —CO2R6;
• R13 is —NR1R12 or —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 —NR1R2.