Kumar Dinesh, Carron Rosalia, La Calle Carmen De, Jindal Dharam Paul, Bansal Ranju
University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh-160014, India.
Acta Pharm. 2008 Dec;58(4):393-405. doi: 10.2478/v1007-008-0021-4.
The present study describes the synthesis and pharmacological evaluation of 2-substituted-6-(4-acylaminophenyl)-4,5-dihydropyridazin-3(2H)-ones as potent inodilating agents. The synthesis of target compounds 2-4 and 7-11 was achieved by Friedel-Crafts acylation of appropriate anilide derivative with succinic anhydride or methylsuccinic anhydride and subsequent cyclization of intermediary keto acids with various hydrazine derivatives. The newly synthesized pyridazinone derivatives were evaluated for cardiotonic activity using isolated rat atria and for vasorelaxant activity using descending thoracic aortic rings of Wistar rats precontracted with phenylephrine (10-6 mol L-1). 6-(4-Methanesulfonamidophenyl)-2-phenyl-4,5-dihydropyridazin-3(2H)-one (7) exhibited significant inodilatory properties and showed vasorelaxant activity in a nanomolar range (IC50 = 0.08 +/- 0.01 mumol L-1).
本研究描述了2-取代-6-(4-酰氨基苯基)-4,5-二氢哒嗪-3(2H)-酮作为强效血管扩张剂的合成及药理学评价。目标化合物2-4和7-11的合成是通过合适的酰苯胺衍生物与琥珀酸酐或甲基琥珀酸酐进行傅克酰基化反应，随后中间酮酸与各种肼衍生物进行环化反应来实现的。使用离体大鼠心房对新合成的哒嗪酮衍生物进行强心活性评价，并使用预先用去氧肾上腺素(10-6 mol L-1)预收缩的Wistar大鼠胸降主动脉环进行血管舒张活性评价。6-(4-甲磺酰胺基苯基)-2-苯基-4,5-二氢哒嗪-3(2H)-酮(7)表现出显著的血管扩张特性，并在纳摩尔范围内显示出血管舒张活性(IC50 = 0.08 +/- 0.01 μmol L-1)。
