Targeting Ubiquitin-Specific Protease 7 with Novel 5-Amino-Pyrazole Inhibitors: Design, Synthesis, and Biological Evaluation.

ABSTRACT: To further extend the structure-activity relationships (SARs) of the previously published ubiquitin-specific protease 7 (USP-7) inhibitor STIRUR-41, a small library of 5-aminopyrazoles 1a-d and 2a-d is designed and synthesized. The chemical identity of the desired structure is confirmed by nuclear magnetic resonance and single crystal X-ray diffraction analyses. All novel derivatives are tested as potential USP-7 inhibitors and compounds 1a-d block enzyme activity in a dose-dependent manner and with lower IC₅₀ values compared to the lead compound STIRUR-41. Notably, 1d, bearing a meta-trifluoromethylphenyl group linked to the carbamate moiety, proved to be the most active candidate. Conversely, compounds belonging to series 2, which possess greater steric hindrance, exhibit no a

SUBMITTER: Lusardi M 

PROVIDER: S-EPMC12368478 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature