Synthesis, Characterization, and Biological Evaluation of Oxadiazole Derivatives Bearing 5-Phenyl-tetrazole as Osteoclast Differentiation Inhibitors

摘要

Novel oxadiazoles bearing 5-phenyl-tetrazole (5a-k) were designed and efficiently synthesized by treating 2-(5-phenyl-2H-tetrazole-2-yl)acetohydrazide (4) with aromatic carboxylic acids in POCl3 , and their in vitro anti-osteoclastogenic activities were evaluated. In the cell-based osteoclast differentiation model, all compounds (5a-k) inhibited the formation of osteoclasts. In addition, the potential target molecules of compound 5 analogs were predicted with their chemical substructures via a web-based interface, and some of them were found to be related to osteoclast differentiation. Consequently, the scaffold containing oxadiazole-tetrazole in a single molecule and their analogs are of potential use in the design of novel anti-osteoclastogenic therapeutics.