New N-(4-(indoline-1-sulfonyl)-phenyl)-amino acid derivatives, are peroxisome proliferator activated receptor delta activators used e.g. for treating or preventing stroke, arteriosclerosis, coronary heart disease and dyslipidemia

摘要

N-(4-(Indoline-1-sulfonyl)-phenyl)-amino acid derivatives (I) are new. New N-(4-(indoline-1-sulfonyl)-phenyl)-amino acid derivatives of formula (I) and their salts, solvates and solvated salts are new. [Image] R1>phenyl or Het (both optionally substituted by 1-3 halo, CN, NO2, alkyl (optionally substituted by OH), alkoxy, CF3, OCF3, alkylsulfonyl, alkanoyl, alkoxycarbonyl, COOH, NH2, 1-6C acylamino or mono- or di-alkylamino); Het : 5- or 6-membered heteroaryl containing 1 or 2 N, O and/or S heteroatom(s); R2>-R4>, R7>, R8>H or A, or CR2>R3>3-7 membered, spiro-linked cycloalkyl; A : 1-4C alkyl; R5>H, A, OA or halo; R6>alkyl, 3-8C cycloalkyl, alkanoyl, alkylsulfonyl or alkoxycarbonyl, and R9>H or group hydrolyzable to H; alkyl moieties have 1-6C unless specified otherwise. An independent claim is included for the preparation of (I). ACTIVITY : Cerebroprotective; Antiarteriosclerotic; Cardiant; Antilipemic; Vasotropic; Anorectic; Antidiabetic; Hypotensive; Hepatotropic; Antiinflammatory; Cytostatic. MECHANISM OF ACTION : Peroxisome proliferator activated receptor-delta (PPAR-delta ) activator. In a cellular transactivation assay for identifying PPAR-delta activators, using a GAL4-PPAR-delta chimera co-transfected with a reporter construct and stably expressed in Chinese hamster ovary cells, results showed that N-(4-((3,3-dimethyl-5-(4-(trifluoromethyl)-phenyl)-2,3-dihydro-1H-indol-1-yl)-sulfonyl)-phenyl)-N-methylglycine (Ia) exhibited an EC50 value of 8.5 nM.