7-Amino-3-phenyl-2-methyl-pyrazolopyrimidine derivatives inhibit human rhinovirus replication.

Antiviral compound Enterovirus Human rhinovirus PI4KIIIβ Pyrazolo-pyrimidine

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:
17 Jul 2024
Historique:
received: 14 05 2024
revised: 15 07 2024
accepted: 15 07 2024
medline: 21 7 2024
pubmed: 21 7 2024
entrez: 20 7 2024
Statut: aheadofprint

Résumé

Small molecules that exhibit broad-spectrum enteroviral inhibitory activity by targeting viral replication proteins are highly desired in antiviral drug discovery studies. To discover new human rhinovirus (hRV) inhibitors, we performed a high-throughput screening of 100,000 compounds from the Korea Chemical Bank library. This search led to identification of two phosphatidylinositol-4-kinase IIIβ (PI4KIIIβ) inhibitors having the pyrazolo-pyrimidine core structure, which display moderate anti-rhinoviral activity along with mild cytotoxicity. The results of a study aimed at optimizing the activity of the hit compounds showed that the pyrazolo-pyrimidine derivative 6f exhibits the highest activity (EC

Identifiants

pubmed: 39032404
pii: S0223-5234(24)00570-1
doi: 10.1016/j.ejmech.2024.116690
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

116690

Informations de copyright

Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Prashant Chakrasali (P)

Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology, Daejeon, 34114, Republic of Korea; Department of Medicinal and Pharmaceutical Chemistry, University of Science and Technology, Daejeon, 34113, Republic of Korea.

Dasom Hwang (D)

Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology, Daejeon, 34114, Republic of Korea.

Joo-Youn Lee (JY)

Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology, Daejeon, 34114, Republic of Korea.

Eunhye Jung (E)

Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology, Daejeon, 34114, Republic of Korea.

Hye Lim Lee (HL)

Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology, Daejeon, 34114, Republic of Korea.

Alba Reneesh (A)

Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology, Daejeon, 34114, Republic of Korea; Department of Medicinal and Pharmaceutical Chemistry, University of Science and Technology, Daejeon, 34113, Republic of Korea.

Adam Skarka (A)

Department of Chemistry, Faculty of Science, University of Hradec Kralove, Czech Republic.

Kamil Musilek (K)

Department of Chemistry, Faculty of Science, University of Hradec Kralove, Czech Republic.

Nhung Hong Nguyen (NH)

Department of Medicinal and Pharmaceutical Chemistry, University of Science and Technology, Daejeon, 34113, Republic of Korea; Data Convergence Drug Research Center, Korea Research Institute of Chemical Technology, Daejeon, 34114, Republic of Korea.

Jin Soo Shin (JS)

Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology, Daejeon, 34114, Republic of Korea. Electronic address: jsshin@krict.re.kr.

Young-Sik Jung (YS)

Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology, Daejeon, 34114, Republic of Korea; Department of Medicinal and Pharmaceutical Chemistry, University of Science and Technology, Daejeon, 34113, Republic of Korea. Electronic address: ysjung@krict.re.kr.

Classifications MeSH