Quinazoline derivatives as VEGF inhibitors

A compound of the formula I:

• wherein:
• Z represents —O—, —NH— or —S—;
• m is an integer from 1 to 5 with the proviso that where Z is —NH— m is an integer from 3 to 5;
• R1 represents hydrogen, hydroxy, halogeno, nitro, trifluoromethyl, cyano, C1-3alkyl C1-3alkoxy, C1-3alkylthio, or —NR5R6 (wherein R5 and R6, which may be the same or different, each represents hydrogen or C1-3alkyl);
• R2 represents hydrogen, hydroxy, halogeno, methoxy, amino or nitro;
• R3 represents hydroxy, halogeno, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl, cyano, amino or nitro;
• X1 represents —O—, —S—, —SO—, —SO2—, —NR7—, —NR8CO—, —CONR9—, —SO2NR10— or —NR11SO2—, (wherein R7, R8, R9, R10 and R11 each represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl);
• R4 is selected from one of the following seven groups:
• 1) hydrogen, C1-5hydroxyalkyl, C1-5fluoroalkyl, C1-5 aminoalkyl;
• 2) C1-5alkylX2COR12 (wherein X2 represents —O— or —NR13— (in which R13 represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R12 represents C1-3alkyl, —NR14R15 or —OR16 (wherein R14, R15 and R16 which may be the same or different each represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl));
• 3) C1-5alkylX3R17 (wherein X3 represents —O—, —S—, —SO—, —SO2—, —OCO—, —NR18CO—, —CONR19—, —SO2NR20, —NR21SO2— or —NR22— (wherein R18, R19, R20, R21 and R22 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R17 represents hydrogen, C1-3alkyl, cyclopentyl, cyclohexyl or a 5 or 6 membered saturated heterocyclic group with one or two heteroatoms, selected independently from O, S and N, which C1-3alkyl group may bear one or two substituents selected from oxo, hydroxy, halogeno and C1-4alkoxy and which cyclic group may bear one or two substituents selected from oxo, hydroxy, halogeno, C1-4alkyl, C1-4hydroxyalkyl and C1-4alkoxy);
• 4) C1-5alkylR23 (wherein R23 is a 5 or 6 membered saturated heterocyclic group with one or two heteroatoms, selected independently from O, S and N, which heterocyclic group may bear one or two substituents selected from oxo, hydroxy, halogeno, C1-4alkyl, C1-4hydroxyalkyl and C1-4alkoxy);
• 5) C2-5alkenylR23 (wherein R23 is as defined hereinbefore);
• 6) C2-5alkynylR23 (wherein R23 is as defined hereinbefore);
• and
• 7) C1-5alkylX4C1-5alkylX5R24 (wherein X4 and X5 which may be the same or different are each —O—, —S—, —SO—, —SO2—, —NR25CO—, —CONR26—, —SO2NR27—, —NR28SO2— or —NR29— (wherein R25, R26, R27, R28 and R29 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R24 represents hydrogen or C1-3alkyl);
• and salts thereof.