Patent DE-102004036314-A1 (DE)
Title: New D-glucopyranosylphenyl-substituted cyclic compounds useful as sodium-dependent glucose cotransporter inhibitors for treating metabolic diseases, e.g. diabetes
Inventor: ECKHARDT MATTHIAS
IPC: C07H3/02
Filed: 2004-07-27
Abstract: D-glucopyranosylphenyl-substituted cyclic compounds (I) are new. D-glucopyranosylphenyl-substituted cyclic compounds of formula (I) and their tautomers, stereoisomers and salts, other than 3-(3-beta -D-glucopyranosyl-4,5-dimethoxybenzyl)-4-(3,4-dimethoxybenzyl)-dihydro-2(3H)-furanone (Ia), are new: Cy : a 5- or 6-membered saturated or monounsaturated ring containing 0-3 heteroatoms (N, O, S) in which 1-2 CH 2groups can be replaced by CO, S, SO or SO 2and C-bonded H atoms can be replaced by F; Z : O, CH 2, CH, NR, CO, S, SO or SO 2, where CH 2and CH are optionally substituted with Me or F; R 1>e.g. H, halo, 1-6C alkyl, 2-6C alkenyl, 2-6C alkynyl, 3-7C cycloalkyl, (3-7C)cycloalkyl(1-3C)alkyl, 5-7C cycloalkenyl, (5-7C)cycloalkenyl(1-3C)alkyl, 1-4C alkylcarbonyl, aroyl; R 2>H, F, Cl, Br, OH, 1-4C (fluoro)alkyl, 1-4C alkoxy, CN or NO 2; R 1>+R 2>3-5C alkylene, 3-5C alkenylene or butadienylene, optionally substituted with F or 1-2 of Cl, OH, 1-3C alkoxy and 1-3C alkyl, where 1-2 CH 2groups can be replaced by O, S, CO, SO, SO 2or NR and 1-2 CH groups can be replaced by N; R 3>R 1>(but not iodo) or Y; R 4>H, F, Cl, CN, NO 2, NH 2, mono- or di(1-3C alkyl)amino, 1-3C alkylcarbonylamino, 1-3C alkyl, 1-3C alkoxy, COOH, 1-3C alkoxycarbonyl, fluoromethyl or fluoromethoxy; R 3>+R 4>2-6C alkylene or 4-6C alkenylene optionally substituted with F or 1-2 of Cl, OH, 1-3C alkoxy and 1-3C alkyl, where 1-2CH 2groups can be replaced by O, S, CO, SO, SO 2or NR; or R 3>+R 4>forms a fused 5- or 6-membered ring optionally substituted with F or 1-2 of Cl, OH, 1-3C alkoxy and 1-3C alkyl, where 1-2 CH 2groups can be replaced by O, S, CO, SO, SO 2or NR and 1-2 CH groups can be replaced by N or a fused aromatic ring can be substituted with 1-2 of L; R 5>H, F, Cl, CN, 1-3C alkyl, 1-3C alkoxy, fluoromethyl or fluoromethoxy; R 4>+R 5>1-4C alkylene or 2-4C alkenylene, optionally substituted with F or 1-2 of Cl, OH, 1-3C alkoxy and 1-3C alkyl, where 1-2 CH 2groups can be replaced by O, S, CO, SO, SO 2or NR; R 6>H, 1-3C alkyl or F; R 4>+R 5>+R 6>3-6C alkanetriyl optionally substituted with F or 1-2 of Cl, OH, 1-3C alkoxy and 1-3C alkyl, where 1-2 CH 2groups can be replaced by O, S, CO, SO, SO 2or NR; Y : e.g. O, CH 2(optionally substituted with F, Cl, 1-6C alkyl, 2-6C alkenyl, 2-6C alkynyl, 3-7C cycloalkyl, 5-7C cycloalkenyl or Y is =C(Ry)DBRb; D : CO or SO 2; Ry : H, F, Cl, CN, CF 3or 1-3C alkyl; B : a bond, O or NR; Rb : e.g. H, 1-6C alkyl, 3-6C alkenyl, 3-6C alkynyl, 3-7C cycloalkyl, 5-7C cycloalkenyl, (3-7C)cycloalkyl(1-3C)alkyl; Rb+B : pyrrolidine, morpholine, piperidine, piperazine of 4-(1-4C alkyl)piperazine; R : H or 1-4C alkyl; L : halo, 1-3C alkyl, CHF 2, CF 3, 1-3C alkoxy, OCHF 2, OCF 3, CN; R7a, R7b, R7c, R7d : H, (1-18C alkyl)carbonyl, (1-18C alkoxy)carbonyl, arylcarbonyl or aryl(1-3C)alkylcarbonyl; aryl : phenyl or naphthyl substituted with 0-2 of L; heteroaryl : e.g. pyrrolyl, furyl, thienyl, imidazolyl or pyridyl. [Image] ACTIVITY : Antidiabetic; Antilipemic; Antiarteriosclerotic; Anorectic; Hypotensive; Cardiant; Antiinflammatory; Antigout. MECHANISM OF ACTION : Sodium-dependent glucose cotransporter (SGLT) inhibitor. Test details are described but no results given.