EP0880508B1 — Quinazoline derivatives as vegf inhibitors

USPTO Abstract

The invention relates to quinazoline derivatives of formula (I)wherein: Z represents -O-, -NH- or -S-; m is an integer from 1 to 5; R1 represents hydrogen, hydroxy, halogeno, nitro, trifluorometlyl, 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-, -CH2-, -S-, -SO-, SO2-, -NR6-, NR8CO-, -CONR9-SO2NR10- or -NR11SO2-, (wherein R7, R8, R9, R10 and R11 each represents C1-3alkyl, C1-3alkoxyC2-3alkyl); R4 represents a group which is alkenyl, alkynyl or optionally substituted alkyl, which alkyl group may contain a heteroatom linking group, which alkenyl, alkynyl or alkyl group may carry a terminal optionally substituted 5 or 6 membered saturated carbocylic or heterocyclic group; and salts thereof, processes for their preparation, pharmaceutical compositions containing a compound of formula (I) or a pharmaceutically acceptable salt thereof as active ingredient the compounds of formula (I) and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.