| abstract |
One aspect of the present invention relates to the design, synthesis and biological activity of novel HIV-1 protease inhibitors, incorporating N-phenyloxazolidine-5-carboxamide into the (hydroxyethylamino) sulfonamide backbone as a P2 ligand. . For example, the present invention relates to inhibitors with variations in the P2 phenyloxazolidine and P2 'phenylsulfonamide moieties. Surprisingly, at P2, compounds with the (S) -enantiomer of substituted phenyl oxazolidine show a highly potent inhibitory activity against the wild type HIV-1 protease. In certain embodiments, the inhibitors of the present invention have a Ki value in the low picomolar (pM) range. In certain embodiments, the inhibitors of the present invention have been shown to be active against a variety of multidrug resistance (MDR) HIV-1 proteases, each presenting a different paradigm of drug resistance. |