SYNTHESIS OF DIPEPTIDE-TYPE HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) PROTEASE INHIBITORS WITH A BINDING UNIT TO GP120

Some dipeptide-type human immunodeficiency virus (HIV) protease inhibi tors derived from KNI-102, with a N-carbomethoxycarbonylprolyl-phenyla lanine benzyl ester (CPF) moiety as a binding site to gp120, were synt hesized. Compounds 11a showed 7-100 times higher HIV protease-inhibito ry activity (11a; IC50 = 0.90 mu g/ml, 1.1 mu M) than the standard com pound 3 or 4 (3; IC50 = 3.7 mu g/ml, 7.7 mu M, 4; IC50 = 75 mu g/ml, 1 55 mu M). Generally, the compounds substituted at the o-position of th e phenoxyacetyl group 7a, 11a, 16a and 21a showed several times higher inhibitory activity than 3.