Synthesis and activity of novel HIV protease inhibitors with improved potency against multiple PI-resistant viral strains.

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Duffy JL, Kevin NJ, Kirk BA, Chapman KT, Schleif WA, Olsen DB, Stahlhut M, Rutkowski CA, Kuo LC, Jin L, Lin JH, Emini EA, Tata JR

Synthesis and activity of novel HIV protease inhibitors with improved potency against multiple PI-resistant viral strains.

Bioorg Med Chem Lett. 2002 Sep 2;12(17):2423-6.

PubMed ID

12161148 [ View in PubMed

]

Abstract

Substitution of the t-butylcarboxamide substituent in analogues of the HIV protease inhibitor (PI) Indinavir with a trifluoroethylamide moiety confers greater potency against both the wild-type (NL4-3) virus and PI-resistant HIV. The trifluoroethyl substituent also affords a slower clearance rate in vivo (dogs); however, this may be due to more potent inhibition of at least two P450 isoforms.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Indinavir	Cytochrome P450 2D6	IC 50 (nM)	>30000	N/A	N/A	Details
Indinavir	Cytochrome P450 3A4	IC 50 (nM)	150	N/A	N/A	Details