University of Agriculture and Veterinary Medicine "Ion Ionescu de la Brad" Iasi, Aleea Mihail Sadoveanu, Iasi, Romania.
Eur J Med Chem. 2013 Sep;67:367-72. doi: 10.1016/j.ejmech.2013.04.069. Epub 2013 Jul 12.
A comprehensive study concerning synthesis, structure and biological activity of new pyridazine-fluorine (PYF) derivatives is presented. The first synthesis of PYF derivatives in phase-transfer catalysis (PTC) under microwave (MW) and conventional thermal heating (TH) is reported. Under MW irradiation the consumed energy decreases considerably, the amount of used solvent in liquid phase is at least five-fold less comparative with conventional TH, while PTC did not use solvents. Consequently these reactions could be considered environmentally friendly. Also, the reaction time decrease substantially and, in some cases, the yields are higher. A feasible explanation for MW efficiency is presented. Regiochemistry and chorochemistry involved in these reactions are also discussed; the reactions are regioselective and chorospecific or choroselective, respectively. Ten new pyridazine-fluorine cycloadducts are obtained. The in vitro antibacterial and antifungal activities of the PYF compounds were tested. Introduction of a trifluoromethyl moiety on the pyridazine skeleton is leading to an increasing of the antimicrobial activity. Structure-activity correlationships have been done.
本文介绍了新型哒嗪-氟（PYF）衍生物的合成、结构和生物活性的综合研究。首次报道了在微波（MW）和传统热加热（TH）下相转移催化（PTC）中哒嗪-氟衍生物的合成。在 MW 照射下，消耗的能量大大减少，与传统 TH 相比，液相中使用的溶剂量至少减少了五倍，而 PTC 则没有使用溶剂。因此，这些反应可以被认为是环保的。此外，反应时间大大缩短，在某些情况下，产率更高。对 MW 效率提出了一种可行的解释。还讨论了这些反应中涉及的区域化学和氯化学；这些反应分别是区域选择性和氯特异性或氯选择性的。得到了十个新的哒嗪-氟环加成物。测试了 PYF 化合物的体外抗菌和抗真菌活性。在哒嗪骨架上引入三氟甲基部分会导致抗菌活性的增加。进行了构效关系研究。
