New substituted dihydropyrazole- and dihydrotriazole derivatives are hypoxia-inducible transcription factor-prolyl-4-hydroxylase inhibitors useful to treat/prevent e.g. cardiovascular diseases, heart-circulation diseases and anemia

摘要

Substituted dihydropyrazole- and dihydrotriazole derivatives (I), and their salts, solvates, and solvates of the salts are new. Substituted dihydropyrazole- and dihydrotriazole derivatives of formula (I), and their salts, solvates, and solvates of the salts are new. A : O or S; D : N or C-R 3>; R 3>phenyl or 5- or 6-membered heteroaryl (both substituted); R 1>naphthyl or 8-10 membered heteroaryl (both substituted); either m, n : 0-3, provided that m+n = 4; R2a, R2b, R2c, R2d : H, F, (1-4C)-alkyl, trifluoromethyl, OH, (1-4C)-alkoxy or amino; L : e.g. -O-, -S-, -SO 2-, -C(=O)-O- or -O-C(=O)-; Het 1>7 heteroaryl groups; and Het 2>6 heteroaryl groups. With provisos. Full Definitions are given in the DEFINITIONS (Full Definitions) Field. Independent claims are included for: (1) the preparations of (I); and (2) a medicament comprising (I) optionally in combination with one or more further active agents. [Image] ACTIVITY : Cardiovascular-Gen; Cardiant; Antianemic; Nephrotropic; Antianginal; Cerebroprotective; Vasotropic; Antiarteriosclerotic; Hypotensive; Respiratory-Gen; Antiarthritic; Antirheumatic; Ophthalmological; Antiparkinsonian; Neuroprotective; Nootropic; Analgesic; Vulnerary; Anabolic; Endocrine-Gen; Antidiabetic; Antimicrobial; Antiinflammatory. MECHANISM OF ACTION : Hypoxia-inducible transcription factor (HIF)-prolyl-4-hydroxylase inhibitor. The ability of (I) to inhibit the activity of HIF-prolyl-4-hydroxylase was tested in-vitro using the method described in Oehme F., Jonghaus W., Narouz-Ott L., Huetter J., Flamme I., Anal. Biochem. 330 (1), 74-80 (2004). The results showed that (I) exhibited an IC 50value of = 30 mu M.