A solvent free, four-component synthesis and 1,3-dipolar cycloaddition of 4(H)-pyrans with nitrile oxides: Synthesis and discovery of antimycobacterial activity of enantiomerically pure 1,2,4-oxadiazoles

被引：35

作者：

Almansour, Abdulrahman I. ^{[1
]}

Kumar, Raju Suresh ^{[1
]}

Arumugam, Natarajan ^{[1
]}

Sriram, Dharmarajan ^{[2
]}

机构：

[1] King Saud Univ, Dept Chem, Coll Sci, Riyadh 11451, Saudi Arabia

[2] Birla Inst Technol & Sci Pilani, Med Chem & Antimycobacterial Res Lab, Pharm Grp, Hyderabad 500078, Andhra Pradesh, India

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2012年 / 53卷

关键词：

Antitubercular activity; Mycobacterium tuberculosis; Multi-drug resistant tuberculosis; 1,3-Dipolar cycloaddition; Pyrans; 1,2,4-Oxadiazoles; RESISTANT TUBERCULOSIS; AGONISTS; RECEPTOR; ACETYLCHOLINESTERASE; DISPIROPYRROLIDINES; FLUOROQUINOLONES; OXADIAZOLES; DERIVATIVES; INHIBITORS; LIGANDS;

D O I：

10.1016/j.ejmech.2012.04.021

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Four-component reactions of (R)-1-(1-phenylethyl)tetrahydro-4(1H)-pyridinone, aromatic aldehydes and malononitrile in a 1:2:1 molar ratio in the presence of solid sodium ethoxide under solvent free conditions afforded an inseparable mixture of two diastereomeric 4(H)-pyrans in near quantitative yields. These compounds upon 1,3-dipolar cycloaddition with nitrile oxides furnished two enantiomerically pure 1,2,4-oxadiazoles in moderate yields, which were screened for in vitro activity against Mycobacterium tuberculosis H37Rv (MTB) and multi-drug resistant M. tuberculosis (MDR-TB). Among the compounds screened, compound 10h was found to be the most active in vitro with a MIC value of 0.07 and 0.14 mu M against MTB and MDR-TB respectively. (C) 2012 Elsevier Masson SAS. All rights reserved.

引用

页码：416 / 423

页数：8

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