An Old Target Revisited: Two New Privileged Skeletons and an Unexpected Binding Mode For HIV‐Protease Inhibitors

Favored entrance for the privileged. Two inhibitor structures to address the active site of aspartic proteases have been developed. They are equipped with a central hydroxysulfone unit and, alternatively, a pyrrolidine moiety and decorated with rationally designed side chains. The hydroxysulfones bind to HIV protease as expected, whereas the pyrrolidines display a surprising, previously unreported binding mode.