Design, synthesis and biological activity of N-(2-phenoxy)ethyl imidazo[1,2-a]pyridine-3-carboxamides as new antitubercular agents.


Journal

European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510

Informations de publication

Date de publication:
15 Sep 2019
Historique:
received: 29 03 2019
revised: 13 06 2019
accepted: 13 06 2019
pubmed: 24 6 2019
medline: 8 10 2019
entrez: 24 6 2019
Statut: ppublish

Résumé

A series of N-(2-phenoxy)ethyl imidazo[1,2-a]pyridine-3-carboxamides (IPAs), based on the structure of WZY02 discovered in our lab, were designed and synthesized as new anti-TB agents. Results reveal that many of them exhibit excellent in vitro inhibitory activity with low nanomolar MIC values against both drug-sensitive MTB strain H37Rv and drug-resistant clinical isolates. Compounds 15b and 15d display good safety and pharmacokinetic profiles, suggesting their promising potential to be lead compounds for future antitubercular drug discovery.

Identifiants

pubmed: 31229874
pii: S0223-5234(19)30565-3
doi: 10.1016/j.ejmech.2019.06.038
pii:
doi:

Substances chimiques

Antitubercular Agents 0
Imidazoles 0
Pyridines 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

715-725

Informations de copyright

Copyright © 2019 Elsevier Masson SAS. All rights reserved.

Auteurs

Apeng Wang (A)

Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.

Kai Lv (K)

Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.

Linhu Li (L)

Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.

Hongtao Liu (H)

Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China; Department of Pharmacy, Hebei General Hospital, Hebei, Shijiazhuang, 050051, China.

Zeyu Tao (Z)

Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.

Bin Wang (B)

Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Department of Pharmacology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing, 100149, China.

Mingliang Liu (M)

Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. Electronic address: lmllyx@126.com.

Chao Ma (C)

Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.

Xican Ma (X)

Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.

Bing Han (B)

Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.

Aoyu Wang (A)

Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.

Yu Lu (Y)

Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Department of Pharmacology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing, 100149, China. Electronic address: luyu4876@hotmail.com.

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Classifications MeSH