New heteroaromatic compounds are hypoxia-inducible factor inhibitors useful to treat and/or prevent e.g. cancer or tumor diseases, heart attack, arrhythmia, stroke, psoriasis, diabetic retinopathy, rheumatoid arthritis and polycythemia

摘要

Heteroaromatic compounds (I) or their salts, solvates or solvate of the salts are new. Heteroaromatic compounds of formula (I) or their salts, solvates or solvate of the salts are new. Ring A : phenyl or pyridyl ring; ring B : e.g. 1H-pyrazole group, 1H-imidazole group or 1H-pyrrole group; a : connection point with the adjacent CH 2-group; aa : connection point with the ring (D); ring D : e.g. [1,2,4]oxadiazole group or [1,3,4]oxadiazole group; aaa : connection point with the ring (B); aaaa : connection point with the ring (E); ring E : phenyl or pyridyl ring; R 1 : e.g. H, halo, CN or (1-6C)-alkyl; R 2 : e.g. H, F, Cl or CN; R 3 : CH 3, C 2H 4 or CF 3; R 4 : e.g. H, halo, CN, pentafluorothio or (1-6C)-alkyl; R 5 : F, Cl, CN, CH 3, CF 3 or OH; and n : 0-2. Full Definitions are given in the DEFINITIONS (Full Definitions) Field. Independent claims are included for: (1) a medicament comprising (I) in combination with one or more inert, non-toxic auxiliary agent; and (2) the preparation of (I). [Image] ACTIVITY : Antiapoptotic; Cytostatic; Cardiant; Vasotropic; Antiarrhythmic; Cerebroprotective; Antipsoriatic; Ophthalmological; Antiinflammatory; Antiarthritic; Antirheumatic; Hemostatic; Vulnerary. MECHANISM OF ACTION : Hypoxia-inducible factor inhibitor. The ability of (I) to inhibit hypoxia-inducible factor was tested in HCT 116 cells using hypoxia-inducible factor luciferase assay. The results showed that 5-({3-[3-(4-tert.butylphenyl)-1,2,4-oxadiazol-5-yl]-5-methyl-1H-pyrazol-1-yl}methyl)-N-methyl-pyridin-2-amine exhibited an IC 5 0 value of 0.3 nmole/l.