Cinnoline compounds.

摘要

The invention relatest to compounds of the formula (I) wherein either any one of G₁, G₂, G₃, G₄ and G₅ is nitrogen and the other four are -CH-, or G₁, G₂, G₃, G₄ and G₅ are all -CH-; Z is -O-, -NH-, -S-, -CH₂- or a direct bond; Z is linked to any one of G₁, G₂, G₃ and G₄ which is a free carbon atom; n is an integer from 0 to 5; any of the substitutents R¹ may be attached at any free carbon atom of the indole, azaindole or indazole group; m is an integer from 0 to 3; R^a represents hydrogen; R^b represents hydrogen or another value as defined herein; R¹ represents hydrogen, oxo, hydroxy, halogeno, C_1-4alkyl, C_1-4alkoxy, C_1-4alkoxy, C_1-4-alkyl, aminoC_1-4alkyl, C_1-3alkylaminoC_1-4alkyl, di(C_1-3alkyl)aminoC_1-4alkyl, -C_1-5alkyl(ring B) wherein ring B is selected from azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, N-methylpiperazinly, N-ethylpiperazinyl, morpholino and thiomorpholino; R² represents hydrogen, hydroxy, halogeno, cyano, nitro, trifluoromethyl, C_1-3alkyl, C_1-3alkoxy, C_1-3aklylsulphanyl, -NR³R⁴ (wherein R³ and R⁴, which may be the same or different, each represents hydrogen or C_1-3alkyl), or R⁵X¹- (wherein R⁵ and X¹ are as defined herein) and salts thereof, 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 the use of a compound of formula I in the manufacture of medicament for the production of an antiangiogenic and/or vascular permeability reducing effect in warm-blooded animals. 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.