NOVEL HETEROCYCLIC COMPOUND AND MEDICINAL USE THEREOF

摘要

New tetrahydroisoquinoline-carboxylic acid compounds (I). Tetrahydroquinoline compounds of formula (I) and their salts are new. [Image] R 1H or 1-6C alkyl; R 2H, COR 3, COCR 4=CR 4R 5, COCCR 6, COCH=Cyc, aryl, 1-6C alkyl, 1-6C haloalkyl, 2-6C alkenyl, 3-8C cycloalkyl, 3-8C cycloalkyl-1-3C alkyl or optionally substituted aryl-1-3C alkyl; Cyc : 3-8C cycloalkylene; R 32-6C alkyl or 2-6C haloalkyl; R 4H or 1-4C alkyl; R 51-8C alkyl, 2-8C alkenyl, aryl or heteroaromatic; R 61-8C alkyl; Y : -ON=CR 14R 15; R 7H or 1-4C alkyl; R 85-8C alkyl, 4-8C cycloalkyl 1-4C alkylthio-1-6C alkyl, CR 9=CR 9R 10, NR 11COR 12, ZR 13or CH=Cyc; R 9, R 11, R 14H or 1-4C alkyl; R 101-6C alkyl, 1-6C haloalkyl, 2-8C alkenyl, aryl, heteroaromatic, 3-8C cycloalkyl, 3-8C cycloalkyl-1-3C alkyl, 1-4C alkoxy-1-6C alkyl, 1-4C alkylthio-1-6C alkyl or NR 9R 9-1-6C alkyl; R 121-6C alkyl or aryl; R 131-6C alkyl or aryl; Z, X : O or SR 15; ACTIVITY : Antidiabetic; Antilepic; Antiarteriosclerotic; Anorectic, Antiinflammatory; Hypoglycemic. Administration of 2-(2,4-hexadienoyl)-7-[2-(5-methyl-2-(trans-1-hepten-1-yl)oxazol-4-yl)ethoxy]-1,2,3,4-tetrahydroisoquinoline-(3S)-carboxylic acid (Ia) to db/db mice at 3 mg/kg/day orally reduced blood glucose levels by 57.2% and blood triglyceride levels by 78.1% after 2 weeks. MECHANISM OF ACTION : PPAR-Antagonist;.