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

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

  • Bioorg Med Chem Lett. 2016 May 15;26(10):2464-2469. doi: 10.1016/j.bmcl.2016.03.106.
Timothy J Miles 1,  Alan J Hennessy 2,  Ben Bax 3,  Gerald Brooks 4,  Barry S Brown 5,  Pamela Brown 2,  Nathalie Cailleau 4,  Dongzhao Chen 5,  Steven Dabbs 2,  David T Davies 4,  Joel M Esken 5,  Ilaria Giordano 6,  Jennifer L Hoover 5,  Graham E Jones 4,  Senthill K Kusalakumari Sukmar 5,  Roger E Markwell 4,  Elisabeth A Minthorn 7,  Steve Rittenhouse 5,  Michael N Gwynn 5,  Neil D Pearson 5
Affiliations

Affiliations

  • 1 Diseases of the Developing World CEDD, GlaxoSmithKline, Calle Severo Ochoa, 2, 28760 Tres Cantos, Madrid, Spain. Electronic address: [email protected].
  • 2 Infectious Diseases CEDD, GlaxoSmithKline, Gunnels Wood Road, Stevenage SG1 2NY, UK.
  • 3 Platform Technology & Science, GlaxoSmithKline, Gunnels Wood Road, Stevenage SG1 2NY, UK.
  • 4 Infectious Diseases CEDD, GlaxoSmithKline, Third Avenue, Harlow CM19 5AW, UK.
  • 5 Infectious Diseases CEDD, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA 19426, USA.
  • 6 Diseases of the Developing World CEDD, GlaxoSmithKline, Calle Severo Ochoa, 2, 28760 Tres Cantos, Madrid, Spain.
  • 7 Oncology TA, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA 19426, USA.
PMID: 27055939 DOI: 10.1016/j.bmcl.2016.03.106
Abstract

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.

Keywords

Antibacterials; Bacterial type IIA topoisomerase; GSK945237; In vivo efficacy; NBTI; Pharmacokinetic; Tricyclics.

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