QUINAZOLINE DERIVATIVES

摘要

The invention relates to the use of compounds of the formula I: wherein: ring C is a 5-6 membered heterocyclic moiety; Z is -O-, -S-, or -CH₂-; R¹ is hydrogen, C_1-4alkyl, C_1-4alkoxymethyl, di(C_1-4)alkoxy)methyl, C_1-4alkanoyl, trifluoromethyl, cyano, amino, C_2-5alkenyl, C_2-5alkynyl, carboxy, C_3-7cycloalkyl, C_3-7-cycloalkylC_1-3alkyl, or an optionally substituted group selected from phenyl, benzyl, phenylC_2-4alkyl and a 5-6 membered heterocyclic group; n is an integer from 0 to 5; m is an integer from 0 to 3; R² represents hydrogen, hydroxy, halgeno, cyano, nitro, trifluoromethyl, C_1-3alkyl, C_1-3alkoxy, C_1-3alkylsulphanyl, -NR³R⁴ (wherein R³ and R⁴, which may be the same or different, each represents hydrogen or C_1-3alkyl), or R⁵X¹- (wherein X¹ represents a direct bond, -CH₂-, or a heteroatom linker group and R⁵ is an alkyl, alkenyl or alkynyl chain optionally substituted by for example hydroxy, amino, nitro, alkyl, cycloalkyl, alkoxyalkyl, or an optionally substituted group selected from pyridone, phenyl and a heterocyclic ring, which alkyl, alkenyl or alkynyl chain may have a heteroatom linker group, or R⁵ is an optionally substituted group selected from pyridone, phenyl and a heterocyclic ring, and salts thereof, in the manufacture of a medicament for use in the production of an antiangiogenic and/or vascular permeability reducing effect in warm-blooded animals, processes for the preparation of such compounds, pharmaceutical compositions containing a compound of formula I or a pharmaceutically acceptable salt thereof as active ingredient and compounds of formula I. 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.