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

Authors
Patel, M Ko, SS McHugh, RJ Markwalder, JA Srivastava, AS Cordova, BC Klabe, RM Erickson-Viitanen, S Trainor, GL Seitz, SP
Citation
M. Patel et al., Synthesis and evaluation of analogs of Efavirenz (SUSTIVA (TM)) as HIV-1 reverse transcriptase inhibitors, BIOORG MED, 9(19), 1999, pp. 2805-2810
Citations number
7
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
9
Issue
19
Year of publication
1999
Pages
2805 - 2810
Database
ISI
SICI code
0960-894X(19991004)9:19<2805:SAEOAO>2.0.ZU;2-7
Abstract
Efavirenz (SUSTIVA(TM)) is a potent non-nucleoside reverse transcriptase in hibitor. Due to the observation of breakthrough mutations of the reverse tr anscriptase enzyme during Efavirenz therapy, we sought to develop an optimi zed second generation series. To that end, SAR of the substituents on the a romatic ring was undertaken and the results are summarized here. The 5,6-di fluoro (4f) and the 6-methoxy (4m) substituted benzoxazinones were determin ed to be equipotent, and as a result such substitution patterns will be inc orporated in second generation scaffolds. (C) 1999 DuPont Pharmaceuticals. Published by Elsevier Science Ltd. All rights reserved.