L-735,524: an orally bioavailable human immunodeficiency virus type 1 protease inhibitor.

Abstract:

:To date, numerous inhibitors of the human immunodeficiency virus type 1 protease have been reported, but few have been studied extensively in humans, primarily as a consequence of poor oral bioavailability in animal models. L-735,524 represents a class of human immunodeficiency virus type 1 protease inhibitors, termed hydroxyaminopentane amides, that incorporate a basic amine into the hydroxyethylene inhibitor backbone. L-735,524 is a potent inhibitor of virus replication in cell culture and inhibits the protease-mediated cleavage of the viral precursor polyproteins that results in the production of noninfectious progeny viral particles. The compound is effective against viruses resistant to reverse transcriptase inhibitors and is synergistically active when used in combination with reverse transcriptase inhibitors. Most importantly, L-735,524 exhibits good oral bioavailability and plasma pharmacokinetic profiles in two species of laboratory animals by using clinically acceptable formulations. Accordingly, the compound was selected for evaluation of safety and pharmacokinetic studies in humans.

authors

Vacca JP,Dorsey BD,Schleif WA,Levin RB,McDaniel SL,Darke PL,Zugay J,Quintero JC,Blahy OM,Roth E

doi

10.1073/pnas.91.9.4096

subject

Has Abstract,Author List Incomplete

pub_date

1994-04-26 00:00:00

pages

4096-100

issue

9

eissn

0027-8424

issn

1091-6490

journal_volume

91

pub_type

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