Gökçe Mehtap, Sahin Mustafa Fethi, Küpeli Esra, Yeşilada Erdem
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Ankara, Turkey.
Arzneimittelforschung. 2004;54(7):396-401. doi: 10.1055/s-0031-1296990.
A series of 6-substituted-3(2H)-pyridazinone derivatives were synthesized and evaluated for analgesic and anti-inflammatory activities. The structures of these new pyridazinone derivatives were confirmed by their IR, 1H-NMR spectra and elementary analysis. Analgesic and anti-inflammatory activities of the title compounds have been evaluated. Four of the ten tested compounds possessed significant analgesic effects in the phenylbenzoquinone-induced writhing test (PBQ test). The most active derivatives 8a, 8b, 8d, 8e were void of gastric ulcerogenic effect or acute toxicity at the maximal dose (200 mg/kg p.o.). In the carrageenan-induced paw edema model, compound 8d (6- [4- (2-fluorophenyl) piperazin-1-yl]-3(2H)-pyridazinone) showed anti-inflammatory activity similar to that of the standard drug indometacin (CAS 53-86-1). A significant dependence of the anti-inflammatory effect on the substituents was observed; The pharmacological study of these compounds confirms that modification of the chemical group at position 6 of the 3(2H)-pyridazinone ring influences analgesic and anti-inflammatory activities.
合成了一系列6-取代-3(2H)-哒嗪酮衍生物，并对其镇痛和抗炎活性进行了评价。这些新型哒嗪酮衍生物的结构通过红外光谱、1H-核磁共振光谱和元素分析得以确证。对标题化合物的镇痛和抗炎活性进行了评价。在苯醌诱导的扭体试验（PBQ试验）中，所测试的10种化合物中有4种具有显著的镇痛作用。活性最强的衍生物8a、8b、8d、8e在最大剂量（口服200 mg/kg）时无致胃溃疡作用或急性毒性。在角叉菜胶诱导的足跖水肿模型中，化合物8d（6-[4-(2-氟苯基)哌嗪-1-基]-3(2H)-哒嗪酮）显示出与标准药物吲哚美辛（CAS 53-86-1）相似的抗炎活性。观察到抗炎作用对取代基有显著依赖性；这些化合物的药理学研究证实，3(2H)-哒嗪酮环6位化学基团的修饰会影响镇痛和抗炎活性。
