BETULINIC ACID-DERIVATIVES - A NEW CLASS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SPECIFIC INHIBITORS WITH A NEW MODE OF ACTION

A series of omega-undecanoic amides of lup-20(29)-en-28-oic acid deriv atives were synthesized and evaluated for activity in CEM 4 and MT-4 c ell cultures against human immunodeficiency virus type 1 (HIV-1) strai n IIIB/LAI. The potent HIV inhibitors which emerged, compounds 5a, 16a , and 17b, were all derivatives of betulinic acid (3 beta-hydroxylup-2 0(29)-en-28-oic acid). No activity was found against HIV-2 strain ROD. Compound 5a showed no inhibition of HIV-1 reverse transcriptase activ ity with poly(C). oligo(dG) as template/primer, nor did it inhibit HIV -1 protease. Additional mechanistic studies revealed that this class o f compounds interfere with HIV-1 entry in the cells at a postbinding s tep.