1. Naphthyridinone (NTD) integrase inhibitors 4. Investigating N1 acetamide substituent effects with C3 amide groups.
- Author
-
Johns BA, Kawasuji T, Weatherhead JG, Boros EE, Thompson JB, Koble CS, Garvey EP, Foster SA, Jeffrey JL, and Fujiwara T
- Subjects
- Dose-Response Relationship, Drug, HIV Integrase Inhibitors chemical synthesis, HIV Integrase Inhibitors chemistry, Humans, Leukocytes, Mononuclear drug effects, Leukocytes, Mononuclear virology, Molecular Structure, Naphthyridines chemical synthesis, Naphthyridines chemistry, Structure-Activity Relationship, Acetamides chemistry, Amides chemistry, HIV Integrase metabolism, HIV Integrase Inhibitors pharmacology, Naphthyridines pharmacology
- Abstract
A series of N1 acetamide substituted naphthyridinone HIV-1 integrase inhibitors have been explored to understand structure-activity relationships (SAR) with various C3 amide groups. Investigations were evaluated using integrase enzyme inhibition, antiviral activity and protein binding effects to optimize the sub-structures. Lipophilicity was also incorporated to understand ligand lipophilic efficiency as a function of the structural modifications. Three representative analogs were further examined in a peripheral blood mononuclear cell (PBMC) antiviral assay as well as in vitro and in vivo drug metabolism and pharmacokinetic studies., (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF