Synthesis and antitumor activity of 2,5,7-substituted [1,3]thiazolo[4,5-d]pyridazine-4(5H)-ones
Synthesized a series of new 2,5,7-substituted [1,3] thiazole [4,5-d] pyridazine-4 (5H)-ones from 2,7- substituted derivatives [1,3] thiazole [4,5-d] pyridazine-4 (5H)-ones by their alkylation arylmethylchlorides, 2-chloroacetamide and N-alkyl (aryl)-substituted α-chloroacetamide. The structure and purity of the obtained compounds was confirmed by 1 H NMR spectroscopy and liquid chromatography-spectrometric analysis. Investigated the antitumor activity of the synthesized compounds in experiments in vitro and found that the substitution of aryl substituents in the fifth position of the heterocyclic system (7a, b) on the alkyl (7e), alkylamido (7l) or arylamido (7d, fk, m) leads to a decrease sensitivity of cancer cells. Comparison of the mitotic activity of these compounds indicates a significant role in the fifth position on the heterocycle and its specific value. Under the experimental conditions stated in compound concentrations of 10-5 mol / l found the ability to inhibit the growth of malignant cells that cover the entire range of human cancers.
2. Tetsuo Yamasaki, Eiji Kawaminami, Fumi Uchimura et al. A novel synthesis of 2-arylaminothiazolo [4,5-d] pyridazinone // J. Heter. Chem - 1991. -Vol. 28, Issue 4 - P. 859-865.
3. Tornetta B., Guerrera F., Ronsisvalle G. Reazioni ariltioammidi e β-chloroacetonossalato di et. Synthetic di derivatives of thiazolici, thiazolosazinic acid and thiazolopyridazin-4-one // Annali di Chimica. - 1974. - Vol. 64. - P. 477-479.
4. McCluskey A., Finn M., Bowman A. et al. 2,7-Dimethylthiazolo [4,5-d] pyradazine-4- (5H) -thione: A Corticotrophin-Releasing Hormone Type 1 Receptor Agonist // Australian J. Chem. - 2000. - Vol. 53. - P. 905-908.
5. Makki M.S.I., Faidalah H.M. Synthesis and Biological Evaluation of New Fused Thiazolo [4,5-d] Pyridazine Derivatives // J. Chin. Chem Soc. - 1996. - Vol. 43th - no5. - P.433-438.
6. Ollis D., Ramsden C. Mesoionic compounds // Advances in heterocyclic chemistry. - 1976. - No. 19 - P. 30-98.
7. Matiychuk V.С. , Potopnyk MA, Obushak N.D. Molecular design of pyrazolo [3,4-d] pyridazines // J. Organ. chemistry - 2008. - T.44. - Issue 9 - P. 1368-1376.
8. Potok M.A., Cikroba V.E., Matiichuk V.С., Obushak M.D. Synthesis and antitumor activity of 2-aryl-4 - [(hetarylsulfanyl) methyl] -3-methyl-2,6-dihydro-7H-pyrazolo [3,4-d] pyridazine-7-ones // Clinical Pharmacy, Pharmacotherapy and Medical standardization. - 2009. - No. 34.
9. Teicher B. A., Andrews P. A. Anticancer drug development guide: preclinical screening, clinical. - Medical - 2004. - V. 1. - 450 р.
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