Abstract
Design principles are delineated for non-nucleoside inhibitors for HIV-1 reverse transcriptase (NNRTIs). Simultaneous optimization of binding affinity for wild-type RT, tolerance for viral mutations, and physical properties is pursued. Automated lead generation with the growing program BOMB, Monte Carlo simulations with free-energy perturbation theory for lead optimization, and property analysis with QikProp are featured. An initial 30 μM lead has been optimized rapidly to the 10 nM level.
Original language | English (US) |
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Pages (from-to) | 663-667 |
Number of pages | 5 |
Journal | Bioorganic and Medicinal Chemistry Letters |
Volume | 16 |
Issue number | 3 |
DOIs | |
State | Published - Feb 1 2006 |
Keywords
- Anti-HIV drugs
- Computer-aided drug design
- NNRTI
- Structure-based drug design
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry