Novel nevirapine-like inhibitors with improved activity against NNRTI-resistant HIV: 8-heteroarylthiomethyldipyridodiazepinone derivatives

A series of 8-heteroarylthiomethyldipyridodiazepinone derivatives were prepared and evaluated for their antiviral profile against wild type virus and the important K103N/Y181C mutant as an indicator for broad activity. 2,6-Dimethylpyridine derivative 16 was found to have a good pharmacokinetic profi...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2004-02, Vol.14 (3), p.739-742
Hauptverfasser:	Yoakim, C., Bonneau, P.R., Déziel, R., Doyon, L., Duan, J., Guse, I., Landry, S., Malenfant, E., Naud, J., Ogilvie, W.W., O'Meara, J.A., Plante, R., Simoneau, B., Thavonekham, B., Bös, M., Cordingley, M.G.
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Anti-HIV Agents - chemical synthesis Anti-HIV Agents - metabolism Anti-HIV Agents - pharmacology Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral agents Azepines - chemical synthesis Azepines - metabolism Azepines - pharmacology Biological and medical sciences Drug Resistance, Viral HIV Infections - drug therapy HIV Infections - virology HIV Reverse Transcriptase - chemistry HIV-1 - drug effects HIV-1 - enzymology HIV-1 - genetics Humans Medical sciences Metabolic Clearance Rate Microsomes, Liver - drug effects Microsomes, Liver - metabolism Mutation Nevirapine - chemical synthesis Nevirapine - pharmacology Pharmacology. Drug treatments Pyridines - chemical synthesis Pyridines - metabolism Pyridines - pharmacology Rats Reverse Transcriptase Inhibitors - chemical synthesis Reverse Transcriptase Inhibitors - metabolism Reverse Transcriptase Inhibitors - pharmacology Structure-Activity Relationship
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	A series of 8-heteroarylthiomethyldipyridodiazepinone derivatives were prepared and evaluated for their antiviral profile against wild type virus and the important K103N/Y181C mutant as an indicator for broad activity. 2,6-Dimethylpyridine derivative 16 was found to have a good pharmacokinetic profile in spite of poor metabolic stability in rat liver microsomes. Graphic
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2003.11.049