Patent EP-2743270-A1 (EP)
Inventor: VAKALOPOULOS ALEXANDROS
IPC: A61P3/06
Filed: 2010-01-19
Abstract: Alkylamino-substituted dicyanopyridine compounds (I) and their salts, N-oxides, solvates, salts of N-oxide or solvates of N-oxide and salts are new. Alkylamino-substituted dicyanopyridine compounds of formula (I) and their salts, N-oxides, solvates, salts of N-oxide or solvates of N-oxide and salts are new. Either R 1> : H or (1-4C)-alkyl; and R 2> : (1-6C)-alkyl, (2-4C)-alkenyl, (2-4C)-alkynyl or (3-7C)-cycloalkyl, where: (1-6C)-alkyl is optionally substituted by 1-3 F, Cl, CF 3, CF 3O, (1-4C)-alkoxy, (3-7C)-cycloalkyl, (3-7C)-cycloalkoxy, (1-4C)-alkylsulfanyl or (1-4C)-alkylsulfonyl, (2-4C)-alkenyl and (2-4C)-alkynyl is optionally substituted by 1 or 2 F, CF 3, (1-4C)-alkyl, CF 3O or (1-4C)-alkoxy, and (3-7C)-cycloalkyl is optionally substituted by 1 or 2 F, Cl, CF 3, (1-4C)-alkyl, CF 3O or (1-4C)-alkoxy; or R 1>R 2>N : 4-7-membered heterocycle optionally substituted by 1 or 2 F, Cl, oxo, CF 3, (1-4C)-alkyl, CF 3O or (1-4C)-alkoxy; R 3> : H, -C(=O)-C(R 4>)(R 5>)-N(R 7>)(R 6>) (A), -C(=O)-C(R 8>)(R 9>)-N(R 10>)-C(=O)-C(R 11>)(R 12>)-N(R 13>)(R 14>) (B), -C(=O)-C(R 8>)(R 9>)-N(R 10>)-C(=O)-L 1>-N(R 15>)(R 16>) (C), -C(=O)-L 2>-N(R 16>)(R 17>) (D), -C(=O)-L 2>-N(R 19>)-C(=O)-C(R 11>)(R 12>)-N(R 13>)(R 13>) (E) or -C(=O)-L 2>-N(R 19>)-C(=O) -L 1>-N(R 15>)(R 16>) (F); L 1>, L 2> : (2-6C)-alkanediyl; either R 4>, R 8> : H or the side group of a natural amino acid or its homologous or isomer; and R 6>, R 7>, R 13>-R 18> : H or (1-4C)-alkyl; or R 6>R 7>N, R 13>R 14>N, R 15>R 16>N, R 17>R 18>N : a 5- or 6-membered heterocycle optionally substituted by 1 or 2 (1-4C)-alkyl, amino, OH or (1-4C)-alkoxy; or R 7>R 4> : pyrrolidine- or piperidine ring; R 5>, R 9>, R 10>, R 12>, R 19> : H or CH 3; and either R 11> : H or a side group of a natural alpha -amino acid or its homologous or isomer; or R 14>R 11> : pyrrolidine- or piperidine ring. Independent claims are included for: (1) the preparations of (I); and (2) a medicament comprising (I) in combination with one or more further active agent comprising an active agent that modifies fat metabolism, antidiabetic drug, blood pressure reducing agent and antithrombotic active agent. [Image] ACTIVITY : Muscular-Gen.; Cardiant; Vasotropic; Antianginal; Antidiabetic; Analgesic; Antilipemic; Hypotensive; Antiarrhythmic; Antiinflammatory; Anticoagulant; Thrombolytic; Cerebroprotective; Endocrine-Gen.; Antipsoriatic; Antiseborrheic; Dermatological; Ophthalmological; Vulnerary; Virucide; Cardiovascular-Gen.; Neuroprotective; Nootropic; Antiparkinsonian; Anticonvulsant; Antidepressant; Cytostatic; Antiemetic; Gastrointestinal-Gen.; Antiulcer; Immunosuppressive; Antiarthritic; Antirheumatic; Respiratory-Gen.; Antiasthmatic; CNS-Gen.; Nephrotropic; Anorectic; Antithyroid; Anabolic; Osteopathic; Angiogenesis Modulator. MECHANISM OF ACTION : Adenosine A1 receptor agonist; Adenosine A2b receptor agonist. The ability of (I) to agonize adenosine A1 receptor was tested in Chinese hamster ovary cell line. The results showed that 2-({[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methyl}sulfanyl)-6-[(2-fluorethyl)amino]-4-[4-(2-hydroxyethoxy)phenyl]pyridin-3,5-dicarbonitrile exhibited a median effective concentration of 0.05 nM.