Combinatorial diversification of indinavir: In vivo mixture dosing of an HIV protease inhibitor library

Authors
Rano, TA Cheng, Y Huening, TT Zhang, FQ Schleif, WA Gabryelski, L Olsen, DB Kuo, LC Lin, JH Xu, X Olah, TV McLoughlin, DA King, R Chapman, KT Tata, JR
Citation
Ta. Rano et al., Combinatorial diversification of indinavir: In vivo mixture dosing of an HIV protease inhibitor library, BIOORG MED, 10(14), 2000, pp. 1527-1530
Citations number
13
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
10
Issue
14
Year of publication
2000
Pages
1527 - 1530
Database
ISI
SICI code
0960-894X(20000717)10:14<1527:CDOIIV>2.0.ZU;2-0
Abstract
An efficient combination solution-phase/solid-phase route enabling the dive rsification of the P-1', P-2', and P-3 subsites of indinavir has been estab lished. The synthetic sequence can facilitate the rapid generation of HIV p rotease inhibitors possessing more favorable pharmacokinetic properties as well as enhanced potencies. Multiple compound dosing in vivo may also accel erate the identification of potential drug candidates. (C) 2000 Elsevier Sc ience Ltd. All rights reserved.