Privileged Structures Meet Human T‑Cell Leukemia Virus‑1 (HTLV-1): C2‑Symmetric 3,4-Disubstituted Pyrrolidines as Nonpeptidic HTLV‑1 Protease Inhibitors

3,4-disubstituted pyrrolidines originally designed to inhibit the closely related HIV-1 protease were evaluated as privileged structures against HTLV-1 protease (HTLV-1 PR). The most potent inhibitor of this series exhibits two-digit nanomolar affinity and represents, to the best of our knowledge, the most potent nonpeptidic inhibitor of HTLV-1 PR described so far. The X-ray structures of two representatives bound to HTLV-1 PR were determined, and the structural basis of their affinity is discussed.