New heterocyclic oxime derivatives, useful to treat/prevent e.g. type I diabetes, obesity, appetite regulation, anorexia, bulimia, psoriasis, polycystic ovarian syndrome, dementia and osteoporosis, are aldose reductase inhibitors

摘要

Heterocyclic oxime derivatives (I) are new. Heterocyclic oxime derivatives of formula (I) and their enantiomers, diastereomers and acid/base addition salts, are new. R 1 = T1, T2 or 3-8C cycloalkyl; R 2 = H, 1-6C alkyl, T1 or T1-1-6C alkylene; X = H, halo or 1-6C alkyl; R 3, R 4 = H, halo, 1-6C alkyl, 1-6C alkoxy, 1-6C alkylamino or di(1-6C alkyl)amino; D = pyridine core; A = 1-6C alkylene (CH 2 optionally replaced by a heteroatom e.g. O, S or NR a); R a = H or 1-6C alkyl; B 1 = 1-6C alkyl or 2-6C alkenyl (both optionally substituted by CHR 5R 6); R 5 = COOR; R 6 = OR aa; R, R aa = H or 1-6C alkyl (optionally substituted by halo); T1 = aryl (optionally substituted by 1-3 T3) such as optionally partially hydrogenated phenyl, naphthyl or biphenyl; T2 = heteroaryl such as optionally partially hydrogenated 5-10 membered mono- or bicyclic aromatic group containing 1-3 heteroatoms such as O, N or S; T3 = 1-6C (polyhalo)alkyl, 1-6C alkoxy, OH, carboxy, formyl, NR bR c, ester, amido, NO 2, CN or halo; and R b, R c = H, 1-6C alkyl, T1 or T2. Provided that the oxime group of formula R 1-C(=N-OR 2)- can be in Z or E configuration. Independent claims are included for: (1) preparations of (I); (2) a fused hexahydro-indole derivative of formula (IV); (3) compositions comprising (I) or (IV) or their acid/base additive salts, optionally in combination with excipients; and (4) a combination (Q) comprising (I) and an antioxidant agent. [Image] [Image] ACTIVITY : Antidiabetic; Antilipemic; Metabolic; Cardiovascular-Gen.; Cardiant; Vasotropic; Nephrotropic; Ophthalmological; Antipsoriatic; Gynecological; Nootropic; Osteopathic; Muscular-gen.; Antiinflammatory; Antiarteriosclerotic; Anorectic; Anabolic; Eating-Disorders-Gen; Cytostatic. MECHANISM OF ACTION : Aldose reductase inhibitor.