Synthesis, antitubercular activity, and SAR study of N-substituted-phenylamino-5-methyl-1H-1,2,3-triazole-4-carbohydrazides
Synthesis, antitubercular activity, and SAR study of N-substituted-phenylamino-5-methyl-1H-1,2,3-triazole-4-carbohydrazides
复制标题
DOI：
10.1016/j.bmc.2011.07.035
复制
发表时间：
2011-09-15
影响因子：
3.5
通讯作者：
Cunha, Anna C.
中科院分区：
文献类型：
--
作者：
Jordao, Alessandro K.;Sathler, Plinio C.;Cunha, Anna C.
结核病的治疗仍然是一个挑战，需要新的抗结核药物，由于多重耐药分枝杆菌菌株的出现。本文报道了N-取代苯胺基-5-甲基-1H-1，2，3-三唑-4-碳酰肼类化合物（8a-b，8 e-f，8i-j和8 n-o）及新类似物（8 c-d，8 g-h，8l-m和8 p-q）的合成、抗结核活性和理论分析。这些衍生物以良好的产率合成，其中一些显示出有希望的抗结核谱。有趣的是，N-酰腙（NAH）8 n对结核分枝杆菌H37 Rv菌株的效力最强（MIC = 2.5 μ g/mL），与目前市场上的药物相似或更好。理论构效关系研究表明，呋喃环和电负性基团（NO2）的存在以及R位上的低亲脂性和小体积基团是该类化合物抗结核活性的重要结构特征。报道了这些物质的核磁共振谱、红外光谱和元素分析。(C)2011爱思唯尔有限公司保留所有权利。
Tuberculosis treatment remains a challenge that requires new antitubercular agents due to the emergence of multidrug-resistant Mycobacterium strains. This paper describes the synthesis, the antitubercular activity and the theoretical analysis of N-substituted-phenylamino-5-methyl-1H-1,2,3-triazole-4-carbohydrazides (8a-b, 8e-f, 8i-j and 8n-o) and new analogues (8c-d, 8g-h, 8l-m and 8p-q). These derivatives were synthesized in good yields and some of them showed a promising antitubercular profile. Interestingly the N-acylhydrazone (NAH) 8n was the most potent against the Mycobacterium tuberculosis H37Rv strain (MIC = 2.5 mu g/mL) similar to or better than the current drugs on the market. The theoretical structure-activity relationship study suggested that the presence of the furyl ring and the electronegative group (NO2) as well as low lipophilicity and small volume group at R position are important structural features for the antitubercular profile of these molecules. NMR spectra, IR spectra and elemental analyses of these substances are reported. (C) 2011 Elsevier Ltd. All rights reserved.