Design, diversity-oriented synthesis and biological evaluation of novel heterocycle derivatives as non-nucleoside HBV capsid protein inhibitors.
Antiviral Agents
/ chemical synthesis
Capsid Proteins
/ antagonists & inhibitors
Dose-Response Relationship, Drug
Drug Design
Hepatitis B e Antigens
/ metabolism
Hepatitis B virus
/ drug effects
Microbial Sensitivity Tests
Molecular Structure
Pyrazines
/ chemical synthesis
Pyrazoles
/ chemical synthesis
Pyridines
/ chemical synthesis
Pyrimidines
/ chemical synthesis
Structure-Activity Relationship
Thiazoles
/ chemical synthesis
Virus Replication
/ drug effects
Capsid protein
Diversity-oriented synthesis
HBV
Heterocycle derivatives
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 2020
15 Sep 2020
Historique:
received:
27
03
2020
revised:
16
05
2020
accepted:
18
05
2020
pubmed:
28
7
2020
medline:
2
4
2021
entrez:
27
7
2020
Statut:
ppublish
Résumé
The capsid assembly is a significant phase for the hepatitis B virus (HBV) lifespan and is an essential target for anti-HBV drug discovery and development. Herein, we used scaffold hopping, bioisosterism, and pharmacophore hybrid-based strategies to design and synthesize six series of various heterocycle derivatives (pyrazole, thiazole, pyrazine, pyrimidine, and pyridine) and screened for in vitro anti-HBV non-nucleoside activity. Drug candidate NZ-4 and AT-130 were used as lead compounds. Several compounds exhibited prominent anti-HBV activity compared to lead compound NZ-4 and positive drug Lamivudine, especially compound II-8b, showed the most prominent anti-HBV DNA replication activity (IC
Identifiants
pubmed: 32712535
pii: S0223-5234(20)30467-0
doi: 10.1016/j.ejmech.2020.112495
pii:
doi:
Substances chimiques
Antiviral Agents
0
Capsid Proteins
0
Hepatitis B e Antigens
0
Pyrazines
0
Pyrazoles
0
Pyridines
0
Pyrimidines
0
Thiazoles
0
pyrazole
3QD5KJZ7ZJ
pyrimidine
K8CXK5Q32L
pyridine
NH9L3PP67S
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
112495Informations de copyright
Copyright © 2020 Elsevier Masson SAS. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declared that they have no conflicts of interest to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted.