BETULINIC ACID-DERIVATIVES - A NEW CLASS OF SPECIFIC INHIBITORS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENTRY

A novel series of omega-aminoalkanoic acid derivatives of betulinic ac id were synthesized and evaluated for their activity against human imm unodeficiency virus (HIV). The anti-HIV-1 activity of several members of this new series was found to be in the nanomolar range in CEM 4 and MT-4 cell cultures. The optimization of the omega-aminoalkanoic acid side chain is described. The presence of an amide function within the side chain was found important for optimal activity. RPR 103611 (14g), a statine derivative, was found to be inactive against HIV-1 protease , reverse transcriptase, and integrase as well as on gp120/CD4 binding . ''Time of addition'' experiments suggested interaction with an early step of HIV-1 replication. As syncytium formation, but not virus-cell binding, seems to be affected, betulinic acid derivatives are assumed to interact with the postbinding virus-cell fusion process.