Identification of 2-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)amino)-N-phenylpropanamides as a novel class of potent DprE1 inhibitors.


Journal

Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Titre abrégé: Bioorg Med Chem Lett
Pays: England
ID NLM: 9107377

Informations de publication

Date de publication:
15 06 2020
Historique:
received: 28 01 2020
revised: 05 04 2020
accepted: 11 04 2020
pubmed: 22 4 2020
medline: 13 5 2021
entrez: 22 4 2020
Statut: ppublish

Résumé

The identification of a novel series of DprE1 inhibitors based on a 2-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)amino)-N-phenylpropanamide scaffold is described herein. SAR exploration around the HTS hit 1 led to the identification of multiple analogues with potent DprE1 inhibition and good whole-cell antimycobacterial activity.

Identifiants

pubmed: 32312582
pii: S0960-894X(20)30291-2
doi: 10.1016/j.bmcl.2020.127192
pii:
doi:

Substances chimiques

Antitubercular Agents 0
Bacterial Proteins 0
Enzyme Inhibitors 0
Alcohol Oxidoreductases EC 1.1.-
DprE1 protein, Mycobacterium tuberculosis EC 1.1.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

127192

Informations de copyright

Copyright © 2020 Elsevier Ltd. All rights reserved.

Auteurs

Benjamin C Whitehurst (BC)

GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK; Department of Pure and Applied Chemistry, WestCHEM, University of Strathclyde, Glasgow G1 1XL, UK. Electronic address: ben.whitehurst@astrazeneca.com.

Robert J Young (RJ)

GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK. Electronic address: Rob@blue-burgundy.co.uk.

Glenn A Burley (GA)

Department of Pure and Applied Chemistry, WestCHEM, University of Strathclyde, Glasgow G1 1XL, UK.

Monica Cacho (M)

Global Health R&D, GlaxoSmithKline, Severo Ochoa 2, Tres Cantos, 28760 Madrid, Spain.

Pedro Torres (P)

Global Health R&D, GlaxoSmithKline, Severo Ochoa 2, Tres Cantos, 28760 Madrid, Spain.

Laura Vela-Gonzalez Del Peral (L)

Global Health R&D, GlaxoSmithKline, Severo Ochoa 2, Tres Cantos, 28760 Madrid, Spain.

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Classifications MeSH