TRITERPENE DERIVATIVES THAT BLOCK ENTRY OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INTO CELLS

A series of triterpene compounds characterized by a stringent structur e-activity relationship were identified as potent and selective inhibi tors of human immunodeficiency virus type 1 (HIV-1) replication. Curre ntly studied betulinic derivatives have 50% inhibitory concentrations (IC50) against HIV-1 strain IIIB/LAI in the 10 nM range in several cel lular infection assays but are inactive against HIV-2. These compounds did not significantly inhibit the in vitro activities of several puri fied HIV-1 enzymes. Rather, they appeared to block virus infection at a postbinding, envelope-dependent step involved in the fusion of the v irus to the cell membrane.