新型香豆素曼尼希碱的抗炎和镇痛活性的合成与评价

Synthesis and evaluation of antiinflammatory and analgesic activities of a novel series of coumarin Mannich bases.

作者信息

Bolakatti Girish S, Maddi Veeresh S, Mamledesai Shivalingarao N, Ronad Pradeep M, Palkar Mahesh B, Swamy Shivakumar

机构信息

Department of Pharmaceutical Chemistry, KLE'S College of Pharmacy, Vidyanagar, Hubli, Karnataka, India.

出版信息

Arzneimittelforschung. 2008;58(10):515-20. doi: 10.1055/s-0031-1296551.

DOI:10.1055/s-0031-1296551

PMID:19025062

Abstract

A novel series of coumarinyl Mannich bases (3a-1) have been synthesized by reacting 3-acetyl coumarin (1) with various substituted secondary amines (2a-1) in presence of paraformaldehyde. The structures of the newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR and HRMS (high resolution mass spectral) data. Title compounds were screened for in vivo acute anti-inflammatory activity using the carrageenan-induced rat paw edema assay model. Among the compounds tested, 3-[3-(diethylamino)propanoyl]-2H-chromen-2-one (3a)and 3-[3-(piperidine-1-yl) propanoyl]-2H-chromen-2-one (3c) showed 63.1 and 66.7% inhibition, respectively, as compared to the standard drug diclofenac (CAS 15307-86-5, 68.8%). These potent compounds showed encouraging analgesic andantipyretic activities.

摘要

通过使3-乙酰基香豆素（1）与各种取代的仲胺（2a - 1）在多聚甲醛存在下反应，合成了一系列新型的香豆素基曼尼希碱（3a - 1）。通过红外光谱（IR）、核磁共振氢谱（1H NMR）、核磁共振碳谱（13C NMR）和高分辨率质谱（HRMS）数据对新合成化合物的结构进行了表征。使用角叉菜胶诱导的大鼠足跖肿胀试验模型对目标化合物进行了体内急性抗炎活性筛选。在所测试的化合物中，与标准药物双氯芬酸（CAS 15307 - 86 - 5，抑制率68.8%）相比，3-[3-(二乙氨基)丙酰基]-2H-色烯-2-酮（3a）和3-[3-(哌啶-1-基)丙酰基]-2H-色烯-2-酮（3c）的抑制率分别为63.1%和66.7%。这些活性化合物表现出令人鼓舞的镇痛和解热活性。