746587-17-7Relevant academic research and scientific papers
Cinnoline derivatives and use as medicine
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, (2008/06/13)
The invention relates to the use of cinnoline derivatives of formula (I) wherein Z represents —O—, —NH—, —S— or —CH2—; m is a n integer from 1 to 5; R1represents hydrogen, hydroxy, halogeno, nitro, cyano, trifluoromethyl, Cp1-3alkyl, C1-3alkoxy, C1-3alkylthio or NR6R7(wherein R6and R7, which may be the same or different, each represents hydrogen or C1-3alkyl); R2represents hydrogen, hydroxy, auoro, chioro, methoxy, amino or nitro; R3represents hydroxy, halogeno, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl, cyano, amino or nitro; R4represents hydrogen, hydroxy, halogeno, cyano, nitro, amino, trifluoromethyl, C1-3alkyl or a group R5—X1(wherein X1represents —O—, —CH2—, —S—, —SO—, —SO2—, —NR8CO—, —CONR9—, —SO2NR10—, —NR11SO2— or NR12— (wherein R8, R9, R10, R11and R12each independently represents hydrogen, C1-3alkyl or C1-3alkoxy C2-3alkyl) and R5is an optionally substituted alkyl, carbocylic or heterocylic 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 anti angiogenic and/or vascular permeability reducing effect in a warmn-blooded animal such as a human being, processes for the preparation of such derivatives, pharmnaceutical compositions containing a compound of formula (I) or a pharmnaceutically 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.
