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

共 35 条

[11] Structure-based design of a low molecular weight, nonphosphorus, nonpeptide, and highly selective inhibitor of protein-tyrosine phosphatase 1B [J].

Iversen, LF ;

Andersen, HS ;

Branner, S ;

Mortensen, SB ;

Peters, GH ;

Norris, K ;

Olsen, OH ;

Jeppesen, CB ;

Lundt, BF ;

Ripka, W ;

Moller, KB ;

Moller, NPH .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (14) :10300-10307

[12] A novel three-component tandem protocol for the regioselective synthesis of 1-(2-arylmethyl-5-aryl-3-thienyl)pyrrolidines and piperidines [J].

Karthikeyan, Subramanian Vedhanarayanan ;

Perumal, Subbu ;

Balasubramanian, K. K. .

TETRAHEDRON LETTERS, 2007, 48 (35) :6133-6136

[13] A facile tandem protocol for the regioselective synthesis of novel thienobenzothiazepines [J].

Karthikeyan, Subramanian Vedhanarayanan ;

Perumal, Subbu .

TETRAHEDRON LETTERS, 2007, 48 (13) :2261-2265

[14] A microwave-assisted facile regioselective Fischer indole synthesis and antitubercular evaluation of novel 2-aryl-3,4-dihydro-2H-thieno[3,2-b]indoles [J].

Karthikeyan, Subramanian Vedhanarayanan ;

Perumal, Subbu ;

Shetty, Krithika Arun ;

Yogeeswari, Perumal ;

Sriram, Dharmarajan .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (11) :3006-3009

[15] Echinothiophene, a novel benzothiophene glycoside from the roots of Echinops grijissii [J].

Koike, K ;

Jia, ZH ;

Nikaido, T ;

Liu, Y ;

Zhao, YY ;

Guo, D .

ORGANIC LETTERS, 1999, 1 (02) :197-198

[16] Discovery of antimycobacterial spiro-piperidin-4-ones: An atom economic, stereoselective synthesis, and biological intervention [J].

Kumar, Raju Ranjith ;

Perumal, Subbu ;

Senthilkumar, Palaniappan ;

Yogeeswari, Perumal ;

Sriram, Dharmarajan .

JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (18) :5731-5735

[17] A highly atom economic, chemo-, regio- and stereoselective synthesis, and discovery of spiro-pyrido-pyrrolizines and pyrrolidines as antimycobacterial agents [J].

Kumar, Raju Ranjith ;

Perumal, Subbu ;

Senthilkumar, Palaniappan ;

Yogeeswari, Perumal ;

Sriram, Dharmarajan .

TETRAHEDRON, 2008, 64 (13) :2962-2971

[18] An atom efficient, solvent-free, green synthesis and antimycobacterial evaluation of 2-amino-6-methyl-4-aryl-8-[(E)-arylmethylidene]-5,6,7,8-tetrahydro-4H-pyrano[ 3,2-c]pyridine-3-carbonitriles [J].

Kumar, Raju Ranjith ;

Perumal, Subbu ;

Senthilkumar, Palaniappan ;

Yogeeswari, Perumal ;

Sriram, Dharmarajan .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (23) :6459-6462

[19] Sacrificial azomethine ylide cycloaddition controlled chemoselective nitrile oxide cycloaddition to 1-methyl-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones:: formation of mono-spiro-isoxazolines [J].

Kumar, Raju Ranjith ;

Perumal, Subbu .

TETRAHEDRON, 2007, 63 (49) :12220-12231

[20] A facile synthesis and antimycobacterial evaluation of novel spiro-pyrido-pyrrolizines and pyrrolidines [J].

Kumar, Raju Ranjith ;

Perumal, Subbu ;

Senthilkumar, Palaniappain ;

Yogeeswari, Perumal ;

Sriram, Dharmarajan .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2009, 44 (09) :3821-3829

← 1 2 3 4 →