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

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

An efficient combination solution-phase/solid-phase route enabling the diversification of the P 1′, P 2′, and P 3 subsites of indinavir has been established. The synthetic sequence can facilitate the rapid generation of HIV protease inhibitors possessing more favorable pharmacokinetic properties as...

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Veröffentlicht in:Bioorganic & medicinal chemistry letters 2000-07, Vol.10 (14), p.1527-1530
Hauptverfasser: Rano, Thomas A, Cheng, Yuan, Huening, Tracy T, Zhang, Fengqi, Schleif, William A, Gabryelski, Lori, Olsen, David B, Kuo, Lawrence C, Lin, Jiunn H, Xu, Xin, Olah, Timothy V, McLoughlin, Debra A, King, Richard, Chapman, Kevin T, Tata, James R
Format: Artikel
Sprache:eng
Schlagworte:
Animals
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antiviral agents
Biological and medical sciences
Cell Line
Combinatorial Chemistry Techniques
Dogs
HIV Protease - metabolism
HIV Protease Inhibitors - chemical synthesis
HIV Protease Inhibitors - chemistry
HIV Protease Inhibitors - pharmacokinetics
HIV Protease Inhibitors - pharmacology
Humans
Indinavir - analogs & derivatives
Indinavir - chemical synthesis
Indinavir - chemistry
Indinavir - pharmacokinetics
Indinavir - pharmacology
Medical sciences
Models, Molecular
Molecular Conformation
Molecular Structure
Pharmacology. Drug treatments
T-Lymphocytes
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Zusammenfassung:An efficient combination solution-phase/solid-phase route enabling the diversification of the P 1′, P 2′, and P 3 subsites of indinavir has been established. The synthetic sequence can facilitate the rapid generation of HIV protease inhibitors possessing more favorable pharmacokinetic properties as well as enhanced potencies. Multiple compound dosing in vivo may also accelerate the identification of potential drug candidates.
ISSN:0960-894X
1464-3405
DOI:10.1016/S0960-894X(00)00276-6