CINNOLINE DERIVATIVES AND USE AS MEDICINE

摘要

The invention relates to the use of cinnoline derivatives of formula (I), wherein Z represents -O-, -NH-, -S- or -CH2-; m is an integer from 1 to 5; R<1> represents hydrogen, hydroxy, halogeno, nitro, cyano, trifluoromethyl, C1-3alkyl, C1-3alkoxy, C1-3alkylthio or NR<6>R<7> (wherein R<6> and R<7>, which may be the same or different, each represents hydrogen or C1-3alkyl); R<2> represents hydrogen, hydroxy, fluoro, chloro, methoxy, amino or nitro; R<3> represents hydroxy, halogeno, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl, cyano, amino or nitro; R<4> represents hydrogen, hydroxy, halogeno, cyano, nitro, amino, trifluoromethyl, C1-3alkyl or a group R<5>-X<1> (wherein X<1> represents -O-, -CH2-, -S-, -SO-, -SO2-, -NR<8>CO-, -CONR<9>-, -SO2NR<10>-, -NR<11>SO2- or -NR<12>- (wherein R<8>, R<9>, R<10>, R<11> and R<12> each independently represents hydrogen, C1-3alkyl or C1-3alkoxy C2-3alkyl) and R<5> is an optionally substituted alkyl, carbocyclic or heterocyclic group which may be saturated or unsaturated and may be directly linked to the cinnoline ring or be linked via a carbon chain which may have heteroatom linking groups within it and salts thereof, in the manufacture of a medicament for use in the production of an antiangiogenic and/or vascular permeability reducing effect in a warm-blooded animal such as a human being, processes for the preparation of such derivatives, 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.