New 1,2-disubstituted 3-benzoyl-indolizine derivatives, are fibroblast growth factor inhibitors useful e.g. for treating cancer, cardiovascular or inflammatory diseases or obesity

摘要

1,2-Disubstituted 3-(3,4-disubstituted benzoyl)-indolizine derivatives (I) are new. Indolizine derivatives of formula (I) and their salts are new. [Image] R : H, halo, Me, OH, OA, COOH, COOA, NR 5R 6, NHSO 2A NHCOA, NHCOOA, -O-A'-COOR 7, -O-A'-NR 5R 6, -O(CH 2) nPh' or -CONR 5R 6, where R is in the 6-, 7- or 8-position of the indolizine ring system; A : 1-5C alkyl; A' : 1-5C alkylene; n : 0-5; R 5and R 6H, A or benzyl; R 7H or A; Ph' : phenyl (optionally substituted by one or more of halo, OA, COOH or COOA); R 1OA, COOH, COOA or Ph'; R 2A, 3-6C cycloalkyl or phenyl (optionally substituted by one or more of halo or OA); and R 3and R 4OH, OA, NH 2, COOH, COOA, NO 2, NR 5R 6, NHCOA, NHCOCF 3, CONR 5R 6or CONHOH; provided that if R = H, then R 1is not OA, COOH or COOA unless R 3or R 4= CONR 5R 6or CONHOH. An independent claim is also included for the preparation of (I). ACTIVITY : Cytostatic; cardiant; antiarteriosclerotic; vasotropic; antidiabetic; ophthalmological; antirheumatic; antiarthritic; antiinflammatory; osteopathic; anorectic. (I) are effective against implanted Lewis lung carcinoma in a mouse tumor angiogenesis model at oral doses of 0.1-100 mg/kg (no specific results for individual compounds given in the source material). MECHANISM OF ACTION : Fibroblast growth factor (FGF) inhibitor.