Novel influenza polymerase PB2 inhibitors for the treatment of influenza A infection.
A549 Cells
Amino Acid Sequence
Animals
Antiviral Agents
/ chemistry
Drug Discovery
Humans
Influenza A virus
/ drug effects
Influenza, Human
/ drug therapy
Models, Molecular
Molecular Structure
Protein Binding
Pyridines
/ chemistry
Pyrimidines
/ chemistry
Pyrroles
/ chemistry
RNA-Dependent RNA Polymerase
/ metabolism
Structure-Activity Relationship
Viral Proteins
/ metabolism
Virus Replication
/ drug effects
Antiviral
Flu
Influenza A
Virus
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 10 2019
15 10 2019
Historique:
received:
17
07
2019
revised:
20
08
2019
accepted:
24
08
2019
pubmed:
9
9
2019
medline:
23
10
2020
entrez:
9
9
2019
Statut:
ppublish
Résumé
Exploration of the chemical space of known influenza polymerase PB2 inhibitor Pimodivir, was performed by our group. We synthesized and identified compounds 16a and 16b, two novel thienopyrimidine derivatives displaying anti-influenza A activity in the single digit nanomolar range in cell culture. Binding of these unique compounds in the influenza polymerase PB2 pocket was also determined using molecular modeling.
Identifiants
pubmed: 31493987
pii: S0960-894X(19)30584-0
doi: 10.1016/j.bmcl.2019.126639
pmc: PMC7732027
mid: NIHMS1539188
pii:
doi:
Substances chimiques
Antiviral Agents
0
PB2 protein, Influenzavirus A
0
Pyridines
0
Pyrimidines
0
Pyrroles
0
Viral Proteins
0
pimodivir
DFC121MXC3
RNA-Dependent RNA Polymerase
EC 2.7.7.48
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
126639Subventions
Organisme : NIAID NIH HHS
ID : P30 AI050409
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI132833
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.
Références
Sci Rep. 2018 Jun 25;8(1):9633
pubmed: 29941893
ACS Infect Dis. 2017 Oct 13;3(10):691-694
pubmed: 28892353
J Med Chem. 2006 Jan 26;49(2):534-53
pubmed: 16420040
Antivir Ther. 2018;23(4):335-344
pubmed: 29244026
Lancet. 2005 Oct 1;366(9492):1175-81
pubmed: 16198766
Vaccines (Basel). 2018 Mar 30;6(2):
pubmed: 29601497
ACS Infect Dis. 2018 Mar 9;4(3):218-223
pubmed: 29355011
Antiviral Res. 2009 Jul;83(1):90-3
pubmed: 19501261
ACS Med Chem Lett. 2017 Jan 18;8(2):261-265
pubmed: 28197323
J Infect Dis. 2019 Mar 15;219(7):1026-1034
pubmed: 30428049
J Med Chem. 2014 Aug 14;57(15):6668-78
pubmed: 25019388
ACS Med Chem Lett. 2017 Jan 20;8(2):256-260
pubmed: 28197322
N Engl J Med. 2018 Sep 6;379(10):913-923
pubmed: 30184455
N Engl J Med. 2011 Dec 29;365(26):2541-2
pubmed: 22204735
Chem Biol Drug Des. 2006 Jan;67(1):83-4
pubmed: 16492153
Nucleic Acids Res. 2018 Jan 25;46(2):956-971
pubmed: 29202182