New nitrogen substituted heterocyclic compounds are glycogen synthase kinase 3-beta inhibitors useful e.g. to treat and/or prevent hematological disease, preferably leukopenia, and for ex-vivo increase of adult hematopoietic stem cells

摘要

Nitrogen substituted heterocyclic compounds (I) and their salts, solvates or solvates of the salts, are new. Nitrogen substituted heterocyclic compounds of formula (I) and their salts, solvates or solvates of the salts, are new. U 1>N; W 1>N or CR 1>6>; V 1>CR 1>2>or N; A : CR 1>5>or N; R 1>2>e.g. H, OH or amino; R 1>5>e.g. H, halo or CN; R 1>6>H or CH 3; R1 : e.g. piperidine groups or pyrrolidine groups; and R 2>6-10C-aryl or 5-10-membered heteroaryl. Full Definitions are given in the DEFINITIONS (Full Definitions) Field. An independent claim is included for the preparation of (I). [Image] ACTIVITY : ACTIVITY -Antianemic; Immunostimulant; Neuroprotective; Nootropic; Antiparkinsonian; Neuroleptic; Antidepressant; Tranquilizer; Cerebroprotective; Vasotropic; Hypnotic; Anticonvulsant; Antidiabetic; Analgesic; Antianginal; Anorectic; Nephrotropic; Ophthalmological; Cardiovascular-Gen.; CNS-Gen.; Gastrointestinal-Gen.; Calcium antagonist; Antisickling; Hemostatic; Anticoagulant; Thrombolytic; Immunosuppressive; Immunomodulator; Cytostatic; Antiasthmatic; Antiinflammatory; Respiratory-Gen.; Antiarthritic; Antirheumatic; Antibacterial; Virucide; Fungicide; Anti-HIV; Hepatotropic; Antiparasitic; Antimalarial; Endocrine-Gen.; Vulnerary; Osteopathic; Cardiant; Antiarrhythmic; Antiarteriosclerotic; Hypotensive. MECHANISM OF ACTION : Glycogen synthase kinase 3-beta -inhibitor. The ability of (I) to inhibit glycogen synthase kinase 3-beta was tested using biochemical assay. The results showed that (I), preferably 4-amino-2-[(2-{[6-(2,4-dichlorophenyl)[1,2,4]triazolo[1,5-a]pyrazin-8-yl]amino}ethyl)amino]-1,3-thiazol-5-carbonitrile exhibited an IC 50value of 3.2 nM.