A facile domino protocol for the regioselective synthesis and discovery of novel 2-amino-5-arylthieno-[2,3-b]thiophenes as antimycobacterial agents

被引：49

作者：

Balamurugan, Kamaraj ^{[1
]}

Perumal, Subbu ^{[1
]}

Reddy, Aaramadaka Sunil Kumar ^{[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, Pharm Grp, Med Chem & Antimycobacterial Res Lab, Hyderabad 500078, Andhra Pradesh, India

来源：

TETRAHEDRON LETTERS | 2009年 / 50卷 / 45期

关键词：

Thieno[2,3-b]thiophenes; Domino reactions; Ethyl cyanoacetate; Malononitrile; Morpholine; Sulfur; Anti mycobacterial activity; 4-COMPONENT TANDEM PROTOCOL; SPIRO-PYRIDO-PYRROLIZINES; STEREOSELECTIVE-SYNTHESIS; ALPHA-SULFONAMIDES; INHIBITORS; NONPEPTIDE; DERIVATIVES; DESIGN; POTENT; SAR;

D O I：

10.1016/j.tetlet.2009.08.085

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A series of novel 2-amino-5-arylthieno[2,3-b]thiophenes has been synthesized regioselectively from the reaction of 5-aryldihydro-3(2H)-thiophenones with ethyl cyanoacetate/malononitrile and sulfur powder in the presence of morpholine under thermal as well as microwave irradiation conditions. This transformation presumably Occurs via domino Gewald reaction-dehydrogenation sequence. The 2-amino-5-arylthieno[2,3-b]thiophenes were evaluated for their in vitro activity against Mycobacterium tuberculosis H37Rv (MTB) and multi-drug resistant M. tuberculosis (MDR-TB). Among 12 compounds screened, ethyl 2-amino-5-(1-naphthyl)thieno[2,3-b]thiophene-3-carboxylate was found to be the most active compound with MIC of 1.1 mu M against MTB and MDR-TB. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：6191 / 6195

页数：5

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