Synthesis and anti-HIV activity of new C2 symmetric derivatives designed as HIV-1 protease inhibitors.

The synthesis of several new anti-HIV-1 compounds is described. The new compounds contain a C(2) symmetry axis and a dihidroxyethylene moiety based on the D-tartaric acid back bone. The synthesis of these compounds was achieved in 36-69% overall yields from D-tartaric acid. The protocol included: acetylation of hydroxyl groups, followed by diamide formation and deacetylation or reduction with LiAlH(4). The anti-HIV 1 activities of these substances were evaluated in PM-1 cells, using Indinavir as standard (IC(50) = 0.2 microM). Two amino alcohol derivatives showed good inhibitory activity against the virus, with IC(50) = 2.0 and 4 microM.
(Copyright 2003 Editions scientifiques et médicales Elsevier SAS)