Quinazoline derivatives and pharmaceutical compositions containing them

摘要

The invention relates to quinazoline derivatives of formula (1) wherein m is an integer from 1 to 2; R¹ represents hydrogen, hydroxy, halogeno, nitro, trifluoromethyl, cyano, C_1-3alkyl, C_1-3alkoxy, C_1-3alkylthio, or -NR⁵R⁶ (wherein R⁵ and R⁶, which may be the same or different, each represents hydrogen or C_1-3alkyl); R² represents hydrogen, hydroxy, halogeno, methoxy, amino or nitro; R³ represents hydroxy, halogeno, C_1-3alkyl, C_1-3alkoxy, C_1-3alkanoyloxy, trifluoromethyl, cyano, amino or nitro; X¹ represents -O-, -CH₂-, -S-, -SO-, -SO₂-, -NR⁷CO-, -CONR⁸-, -SO₂NR⁹-, -NR₁₀SO₂- or -NR¹¹- (wherein R⁷, R⁸, R⁹, R¹⁰ and R¹¹ each independently represents hydrogen, C_1-3alkyl or C_1-3alkoxyC_2-3alkyl); R⁴ represents an optionally substituted 5 or 6 membered saturated carbocyclic or heterocyclic group or 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 group selected from alkyl and a 5 or 6 membered saturated carbocyclic 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 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.