Discovery of BI 224436, a Noncatalytic Site Integrase Inhibitor (NCINI) of HIV-1.
Détails
ID Serval
serval:BIB_F1EE56BC58BC
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Discovery of BI 224436, a Noncatalytic Site Integrase Inhibitor (NCINI) of HIV-1.
Périodique
ACS medicinal chemistry letters
ISSN
1948-5875 (Print)
ISSN-L
1948-5875
Statut éditorial
Publié
Date de publication
10/04/2014
Peer-reviewed
Oui
Volume
5
Numéro
4
Pages
422-427
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Résumé
An assay recapitulating the 3' processing activity of HIV-1 integrase (IN) was used to screen the Boehringer Ingelheim compound collection. Hit-to-lead and lead optimization beginning with compound 1 established the importance of the C3 and C4 substituent to antiviral potency against viruses with different aa124/aa125 variants of IN. The importance of the C7 position on the serum shifted potency was established. Introduction of a quinoline substituent at the C4 position provided a balance of potency and metabolic stability. Combination of these findings ultimately led to the discovery of compound 26 (BI 224436), the first NCINI to advance into a phase Ia clinical trial.
Mots-clé
HIV Integrase, LTR DNA 3′-processing, NCINI, allosteric inhibitor
Pubmed
Web of science
Création de la notice
27/08/2024 10:31
Dernière modification de la notice
05/09/2024 9:01