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Papers of the Week

Papers: 3 Jun 2023 - 9 Jun 2023

Basic Science

In Vitro Studies, Pharmacology/Drug Development

Neuropathic Pain

2023 Jun 07

J Med Chem


6-Substituted Triazolyl Benzoxaboroles as Selective Carbonic Anhydrase Inhibitors: Design, Synthesis, and X-ray Crystallography.


Nocentini A, Bonardi A, Bazzicalupi C, Alterio V, Esposito D, Monti SM, Smietana M, De Simone G, Supuran CT, Gratteri P, Winum JY


Benzoxaborole is currently a scaffold of great relevance in medicinal chemistry. In 2016, it was reported to be a new and valuable chemotype for designing carbonic anhydrase (CA) inhibitors. Herein, using an design, we report the synthesis and characterization of substituted 6-(1-1,2,3-triazol-1-yl)benzoxaboroles. 6-Azidobenzoxaborole was described for the first time as a molecular platform to prepare libraries of inhibitors by a copper(I)-catalyzed azide-alkyne cycloaddition a click chemistry strategy. With inhibition constants below 30 nM, some derivatives, such as compound , showed efficacy as selective hCA VII and IX inhibitors. The design hypothesis was validated by crystallographic investigation on the hCA II/ adduct, which provided explanations over the different inhibition behavior observed against the five evaluated hCA isoforms. Overall, this study identified as a new promising lead compound to develop novel anticancer agents targeting the tumor-associated hCA IX but also potent neuropathic pain relievers targeting hCA VII.