Design, synthesis and biological evaluation of α-substituted isonipecotic acid benzothiazole analogues as potent bacterial type II topoisomerase inhibitors

被引：33

作者：

Axford, Lorraine C. ^{[1
]}

Agarwal, Piyush K. ^{[4
]}

Anderson, Kelly H. ^{[1
]}

Andrau, Laura N. ^{[1
]}

Atherall, John ^{[3
]}

Barker, Stephanie ^{[2
]}

Bennett, James M. ^{[2
]}

Blair, Michael ^{[1
]}

Collins, Ian ^{[2
]}

Czaplewski, Lloyd G. ^{[2
]}

Davies, David T. ^{[2
]}

Gannon, Carlie T. ^{[1
]}

Kumar, Dushyant ^{[4
]}

Lancett, Paul ^{[2
]}

Logan, Alastair ^{[2
]}

Lunniss, Christopher J. ^{[1
]}

Mitchell, Dale R. ^{[3
]}

Offermann, Daniel A. ^{[1
]}

Palmer, James T. ^{[1
]}

Palmer, Nicholas ^{[3
]}

Pitt, Gary R. W. ^{[1
]}

Pommier, Stephanie ^{[2
]}

Price, Daniel ^{[2
]}

Rao, B. Narasinga ^{[4
]}

Saxena, Rashmi ^{[4
]}

Shukla, Tarun ^{[4
]}

Singh, Amit K. ^{[4
]}

Singh, Mahipal ^{[4
]}

Srivastava, Anil ^{[4
]}

Steele, Christopher ^{[3
]}

Stokes, Neil R. ^{[2
]}

Thomaides-Brears, Helena B. ^{[2
]}

Tyndall, Edward M. ^{[1
]}

Watson, David ^{[3
]}

Haydon, David J. ^{[2
]}

机构：

[1] Biota Holdings Ltd, Notting Hill, Vic 3168, Australia

[2] Biota Europe Ltd, Begbroke OX5 1PF, Oxon, England

[3] BioFocus, Saffron Walden CB10 1XL, Essex, England

[4] Jubilant Chemsys Ltd, Noida 201301, India

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 24期

关键词：

DNA gyrase; Topoisomerase; Antibacterial;

D O I：

10.1016/j.bmcl.2013.10.058

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The discovery and optimisation of a new class of benzothiazole small molecules that inhibit bacterial DNA gyrase and topoisomerase IV are described. Antibacterial properties have been demonstrated by activity against DNA gyrase ATPase and potent activity against Staphylococcus aureus, Enterococcus faecalis, Streptococcus pyogenes and Haemophilus influenzae. Further refinements to the scaffold designed to enhance drug-likeness included analogues bearing an alpha-substituent to the carboxylic acid group, resulting in excellent solubility and favourable pharmacokinetic properties. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：6598 / 6603

页数：6

共 10 条

[1]

[Anonymous], M7A7 CLIN LAB STAND

[2]

East SP, 2012, RSC DRUG DISCOV, V21, P335, DOI 10.1039/9781849734912-00335

[3]

Haydon D. J., PCT Int. Appl., Patent No. [WO2009/074810, 2009074810]

[4]

Haydon D. J., PCT Int. Appl., Patent No. [WO2009/074812, 2009074812]

[5]

Haydon D.R., Int Pat. Appl., Patent No. [WO2007148093 A1, 2007148093]

[6] DNA gyrase and topoisomerase IV: Biochemical activities, physiological roles during chromosome replication, and drug sensitivities [J].

Levine, C ;

Hiasa, H ;

Marians, KJ .

BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION, 1998, 1400 (1-3) :29-43

[7] Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance [J].

Magiorakos, A. -P. ;

Srinivasan, A. ;

Carey, R. B. ;

Carmeli, Y. ;

Falagas, M. E. ;

Giske, C. G. ;

Harbarth, S. ;

Hindler, J. F. ;

Kahlmeter, G. ;

Olsson-Liljequist, B. ;

Paterson, D. L. ;

Rice, L. B. ;

Stelling, J. ;

Struelens, M. J. ;

Vatopoulos, A. ;

Weber, J. T. ;

Monnet, D. L. .

CLINICAL MICROBIOLOGY AND INFECTION, 2012, 18 (03) :268-281

[8] Preclinical evaluation of novel antibacterial agents by microbiological and molecular techniques [J].

O'Neill, AJ ;

Chopra, I .

EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2004, 13 (08) :1045-1063

[9]

Palmer J. T., PCT Int. Appl., Patent No. [WO2012/045124, 2012045124]

[10]

Stokes N. R., 2013, ANTIMICROB IN PRESS

← 1 →