Discovery of BI 224436, a Noncatalytic Site Integrase Inhibitor (NCINI) of HIV-1.
Details
Serval ID
serval:BIB_F1EE56BC58BC
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Discovery of BI 224436, a Noncatalytic Site Integrase Inhibitor (NCINI) of HIV-1.
Journal
ACS medicinal chemistry letters
ISSN
1948-5875 (Print)
ISSN-L
1948-5875
Publication state
Published
Issued date
10/04/2014
Peer-reviewed
Oui
Volume
5
Number
4
Pages
422-427
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Abstract
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.
Keywords
HIV Integrase, LTR DNA 3′-processing, NCINI, allosteric inhibitor
Pubmed
Web of science
Create date
27/08/2024 11:31
Last modification date
05/09/2024 10:01