New thiadiazole and oxadiazole derivatives are triglyceride biosynthesis inhibitors useful to treat or prevent e.g. obesity, dyslipidemia, hepatic steatosis, insulin resistance, metabolic syndrome, coronary heart disease and hypertension

摘要

Thiadiazole and oxadiazole derivatives (I) and their base or acid addition salts or bases are new. Thiadiazole and oxadiazole derivatives of formula (I) and their base or acid addition salts or bases are new. n : 0-3; p : 0 or 1; D : O or a bond; X : heteroatom comprising O or S; either R1, R2 : H or 1-6C alkyl; or R1R2 : a cycloalkyl group; and Y1 : aryl, heteroaryl, aryloxy, 1-6C alkyl or 3-10C cycloalkyl (all optionally substituted by one or more substituents of halo, 1-6C alkyl or 1-6C alkoxy). Independent claims are included for: (1) the preparation of (I); and (2) 4-cyclohexyl-benzoic acid compound of formula (III), 4-cyclohexyl-benzamide compound of formula (V), 4-cyclohexyloxy-benzamide compound of formula (XXIII), and 4-cyclohexyloxy-benzoic acid compound of formula (XXI). R : -C(R1R2)-Y1 a group; and R1a : a protecting group. [Image] [Image] ACTIVITY : Anorectic; Antilipemic; Antidiabetic; Vasotropic; Metabolic; Hepatotropic; Cardiant; Hypotensive; Dermatological; Neuroprotective; Nootropic; Immunomodulator; Anti-HIV; Antiinflammatory; Gastrointestinal-Gen.; Cytostatic; Analgesic; Antianginal. MECHANISM OF ACTION : Triglyceride biosynthesis inhibitor. The ability of (I) to inhibit triglyceride biosynthesis was tested in vitro. The result showed that (4-{4-[5-(3-fluoro-benzyl)-[1,3,4]thiadiazol-2-ylcarbamoyl]-phenyl}-cyclohexyl)-acetic acid exhibited an IC 5 0 value of 0.046 mu M.