Synthesis and evaluation of benzoxazinones as HIV-1 reverse transcriptase inhibitors. Analogs of Efavirenz (SUSTIVA TM)

• Published in: Bioorganic & medicinal chemistry letters Vol. 9; no. 22; pp. 3221 - 3224
• Main Authors: Patel, Mona, McHugh, Robert J., Cordova, Beverly C., Klabe, Ronald M., Erickson-Viitanen, Susan, Trainor, George L., Ko, Soo S.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15-11-1999; Elsevier
• Subjects: AIDS/HIV; Anti-HIV Agents - chemical synthesis; Anti-HIV Agents - chemistry; Anti-HIV Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Benzoxazines; Biological and medical sciences; Drug Evaluation, Preclinical; HIV Reverse Transcriptase - drug effects; Medical sciences; Oxazines - chemical synthesis; Oxazines - chemistry; Oxazines - pharmacology; Pharmacology. Drug treatments; Reverse Transcriptase Inhibitors - chemical synthesis; Reverse Transcriptase Inhibitors - chemistry; Reverse Transcriptase Inhibitors - pharmacology; Structure-Activity Relationship; Nitro compound; RNA-directed DNA polymerase; HIV-1 virus; Enzyme; Transferases; Retroviridae; Enzyme inhibitor; Lentivirus; Efavirenz; In vitro; Virus; Nucleotidyltransferases; Structure activity relation; Bicyclic compound; Antiviral; Aromatic compound; Fluorine Organic compounds; Human immunodeficiency virus; Chemical synthesis; Oxygen nitrogen heterocycle
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(99)00565-X

Two series of benzoxazinones differing in the aromatic substitution pattern were prepared and evaluated as HIV-1 reverse transcriptase inhibitors. The 5-fluoro (
5a-d) and 6-nitro (
5e-h) substituted compounds displayed activity comparable or better than Efavirenz, the lead structure of the series.
The synthesis and evaluation of analogs of Efavirenz are described.