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5,6,7,8-Tetrahydro-1,6-naphthyridine Derivatives as Potent HIV-1-Integrase-Allosteric-Site Inhibitors.
- Source :
-
Journal of medicinal chemistry [J Med Chem] 2019 Feb 14; Vol. 62 (3), pp. 1348-1361. Date of Electronic Publication: 2019 Jan 18. - Publication Year :
- 2019
-
Abstract
- A series of 5,6,7,8-tetrahydro-1,6-naphthyridine derivatives targeting the allosteric lens-epithelium-derived-growth-factor-p75 (LEDGF/p75)-binding site on HIV-1 integrase, an attractive target for antiviral chemotherapy, was prepared and screened for activity against HIV-1 infection in cell culture. Small molecules that bind within the LEDGF/p75-binding site promote aberrant multimerization of the integrase enzyme and are of significant interest as HIV-1-replication inhibitors. Structure-activity-relationship studies and rat pharmacokinetic studies of lead compounds are presented.
- Subjects :
- Allosteric Site
Crystallography, X-Ray
HIV Infections drug therapy
HIV Integrase Inhibitors chemistry
HIV Integrase Inhibitors therapeutic use
HIV-1 enzymology
HIV-1 physiology
Humans
Naphthyridines chemistry
Naphthyridines therapeutic use
Virus Replication drug effects
HIV Integrase Inhibitors pharmacology
HIV-1 drug effects
Naphthyridines pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1520-4804
- Volume :
- 62
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 30609350
- Full Text :
- https://doi.org/10.1021/acs.jmedchem.8b01473