A facile synthesis and antimycobacterial evaluation of novel spiro-pyrido-pyrrolizines and pyrrolidines

被引：170

作者：

Kumar, Raju Ranjith ^{[1
]}

Perumal, Subbu ^{[1
]}

Senthilkumar, Palaniappain ^{[2
]}

Yogeeswari, Perumal ^{[2
]}

Sriram, Dharmarajan ^{[2
]}

机构：

[1] Madurai Kamaraj Univ, Sch Chem, Dept Organ Chem, Madurai 625021, Tamil Nadu, India

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

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 44卷 / 09期

关键词：

Antimycobacterial activity; Spiro-piperidone; Nitrile oxide; Azomethine ylide; 1,3-Dipolar cycloaddition; STEREOSELECTIVE-SYNTHESIS; DERIVATIVES; CYCLOADDITION; ANTIFUNGAL; DISCOVERY;

D O I：

10.1016/j.ejmech.2009.05.010

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

An efficient synthesis of 1-methyl-3-[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones was achieved by the reaction of 1-methyl-4-piperidone and aromatic aldehydes in the presence of pyrrolidine under solvent-free microwave irradiation. These dipolarophiles upon cycloaddition with nitrile oxide and azomethine ylides afford stereoselectively novel spiro-isoxazolines, pyrrolizines and pyrrolidines respectively in excellent yields. The spiro compounds were screened for their in vitro activity against Mycobacterium tuberculosis H37Rv (MTB), multi-drug resistant M. tuberculosis (MDR-TB) and Mycobacterium smegmatis (MC2) using agar dilution method. Among the synthesized compounds, 1-methyl-4-(2,4-dichlorophenyl)pyrrolo(spiro[2.3 '']oxindole)spiro[3.3']-1'-methylpiperidin-4'-one was found to be the most active with a minimum inhibitory concentration (MIC) of 1.76 and 0.88 mu M against MTB and MDR-TB respectively. (C) 2009 Elsevier Masson SAS. All rights reserved.

引用

页码：3821 / 3829

页数：9

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