Fluorinated Analogues of the p17/p24 Sequence Incorporating 3-fluoro and 3,3-difluoro Phenylalanines as Potential Inhibitors of HIV Protease

The synthesis and activity of a series of fluorinated peptide analogues of the p17/p24 sequence incorporating 3-fluoro and 3,3-difluoro phenylananines at the P₁ position of the scissile bond are described. It was hoped that these might act as potent inhibitors of HIV protease. In fact, none of the compounds studied displayed any anti-HIV activity in vitro. This may be attributed to poor cell penetration of the compounds and metabolic cleavage of their peptide bonds.