Novel tricyclics (e.g., GSK945237) as potent inhibitors of bacterial type IIA topoisomerases

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• 作者：Timothy J. Miles^a ; ^{tim.j.miles@gsk.com" class="auth_mail" title="E-mail the corresponding author} ; Alan J. Hennessy^b ; Ben Bax^c ; Gerald Brooks^d ; Barry S. Brown^e ; Pamela Brown^b ; Nathalie Cailleau^d ; Dongzhao Chen^e ; Steven Dabbs^b ; David T. Davies^d ; Joel M. Esken^e ; Ilaria Giordano^a ; Jennifer L. Hoover^e ; Graham E. Jones^d ; Senthill K. Kusalakumari Sukmar^e ; Roger E. Markwell^d ; Elisabeth A. Minthorn^f ; Steve Rittenhouse^e ; Michael N. Gwynn^e ; Neil D. Pearson^e
• 关键词：Antibacterials ; Bacterial type IIA topoisomerase ; NBTI ; GSK945237 ; Tricyclics ; Pharmacokinetic ; In vivo efficacy
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：15 May 2016
• 年：2016
• 卷：26
• 期：10
• 页码：2464-2469
• 全文大小：1257 K

文摘

During the course of our research on the lead optimisation of the NBTI (Novel Bacterial Type II Topoisomerase Inhibitors) class of antibacterials, we discovered a series of tricyclic compounds that showed good Gram-positive and Gram-negative potency. Herein we will discuss the various subunits that were investigated in this series and report advanced studies on compound 1 (GSK945237) which demonstrates good PK and in vivo efficacy properties.