Brecanavir

703.82300

703.82

E367I8C7FI

DTXSID10185296

C76908

191.60000

5.33740

1.43g/cm3

1.641

Estimated be 97 to 98%

For the treatment of HIV-1 infection in combination with other antiretroviral agents.

Brecanavir is an orally active aspartic protease inhibitor (PI) under investigation by Vertex and GlaxoSmithKline for the treatment of HIV. Test-tube data suggest that it has activity against virus with resistance to the currently available protease inhibitors, and that it is more powerful against wild-type HIV that existing protease inhibitors, being active at concentrations much lower than most existing protease inhibitors. Unlike some other protease inhibitors, brecanavir does not have a significant interaction with the nucleotide reverse transcriptase inhibitor (NtRTI) tenofovir (Viread). In December of 2006 GlaxoSmithKline announced their decision to discontinue the development of brecanavir for the treatment of HIV. The decision was based on issues regarding the formulation of the drug.

Brecanavir, a CYP3A4 substrate, demonstrated low oral bioavailability in animals (0 to 30%), which increased to 60 to 100% following coadministration with oral ritonavir (a potent CYP3A inhibitor).

Brecanavir is a known substrate of CYP450 3A4, the most important cytochrome P450 isoenzyme involved in metabolizing PIs and non-nucleoside reverse transcriptase inhibitors.

Brecanavir inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.

(1S,2R)-3-((1,3-benzodioxol-5-ylsulfonyl)(2-methylpropyl)amino-2-hydroxy-1-((4-(2-methyl-4-thiazolyl)methoxy)phenyl)methylpropyl)carbamic acid, hexahydrofuro(2,3-b)furan-3yl ester