Synthesis and anаlgеsic activity [1,3]thiazolo[4,5-d]pyridazine-4(5h)-ones
Abstract
There was synthesized a series of new [1,3]thiazolo-[4,5-d] pyridazine-4(5Н)-ones from 7-(2-furyl)-2-pyrrolidin-1-yl[1,3]thiazolo[4,5-d]pyridazin-4(5H)-one by alkylation with N-substituted chloroacetamides. Structures and purity of obtained compounds was confirmed by 1H NMR spectroscopy and liquid chromatography spectrometric analysis. Analgesic activity was investigated by in vivo tests on «Hot plate» and «acetic acid cramps» models. It is shown, that electron donor substituents in 4- and 2,4- positions of aryl fragment at the amide nitrogen atom of the 5-th position of the heterocyclic system give stronger analgesic effect of 5-N-substituted 7-(2-furyl)-2-pyrrolidin-1-yl[1,3]thiazolo[4,5-d]pyridazin-4(5H)-ones.
References
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. - V. 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. - V. 53. - P. 905-908.
5. Makki M.S.I., Faidalah H.M. Synthesis and Biological Evaluation of New Fused Tiazolo [4,5-d] Pyridazine Derivatives // J. Chin. Chem Soc. - 1996. - V. 43, N 5. - P. 433-438.
6. Komlos E., Porsresr J., Knole J. Morfin - prostigmin synergismus // Az. Acta Phisiologica. Acad Scient Hungaricae - 1950. - No. 1. - P. 77-83.
7. Wood R. L. Animal models in analgesic testing // Analgesics: Neurochemical, Behavioral and Clinical Perspectives. Kuhar M., Pasternak J. (Eds) Raven Press / New-York. - 1941. - V. 42. - R. 74.
8. Lapach SN, Chubenko AV, Babich P. N. Statistics in science and business. - Kyiv: Morion, - 2002. - 640 p.
9. Demchenko S.A., Smolsky O.S., Lozynsky M.O. Synthesis and antioxidant activity of 2-methyl-7-aryl- [1,3] thiazolo [4,5-d] pyridazine-4 (5H) -on // Farmats. journ - 2009. - No. 3. - P. 59-64.
This work is licensed under a Creative Commons Attribution 4.0 International License.