1,2,4-Oxadiazole-Bearing Pyrazoles as Metabolically Stable Modulators of Store-Operated Calcium Entry.

Autor:	Aprile S; Department of Pharmaceutical Sciences, Università degli Studi del Piemonte Orientale, Largo Donegani 2, 28100 Novara, Italy., Riva B; Department of Pharmaceutical Sciences, Università degli Studi del Piemonte Orientale, Largo Donegani 2, 28100 Novara, Italy.; ChemICare S.r.l., Enne3, Corso Trieste 15/A, 28100 Novara, Italy., Bhela IP; Department of Pharmaceutical Sciences, Università degli Studi del Piemonte Orientale, Largo Donegani 2, 28100 Novara, Italy., Cordero-Sanchez C; Department of Pharmaceutical Sciences, Università degli Studi del Piemonte Orientale, Largo Donegani 2, 28100 Novara, Italy., Avino G; Department of Pharmaceutical Sciences, Università degli Studi di Trieste, Via Giorgieri 1, 34127 Trieste, Italy., Genazzani AA; Department of Pharmaceutical Sciences, Università degli Studi del Piemonte Orientale, Largo Donegani 2, 28100 Novara, Italy., Serafini M; Department of Pharmaceutical Sciences, Università degli Studi del Piemonte Orientale, Largo Donegani 2, 28100 Novara, Italy., Pirali T; Department of Pharmaceutical Sciences, Università degli Studi del Piemonte Orientale, Largo Donegani 2, 28100 Novara, Italy.; ChemICare S.r.l., Enne3, Corso Trieste 15/A, 28100 Novara, Italy.
Jazyk:	angličtina
Zdroj:	ACS medicinal chemistry letters [ACS Med Chem Lett] 2021 Mar 10; Vol. 12 (4), pp. 640-646. Date of Electronic Publication: 2021 Mar 10 (Print Publication: 2021).
DOI:	10.1021/acsmedchemlett.1c00034
Abstrakt:	Store-operated calcium entry (SOCE) is a pivotal mechanism in calcium homeostasis, and, despite still being under investigation, its dysregulation is known to be associated with severe human disorders. SOCE modulators are therefore needed both as chemical probes and as therapeutic agents. While many small molecules have been described so far, their poor properties in terms of drug-likeness have limited their translation into the clinical practice. In this work, we describe the bioisosteric replacement of the ester moiety in pyrazole derivatives with a 1,2,4-oxadiazole ring as a means to afford a class of modulators with high metabolic stability. Moreover, among our derivatives, a compound able to increase the calcium entry was identified, further enriching the library of available SOCE activators. Competing Interests: The authors declare the following competing financial interest(s): B.R. and T.P. are co-founders of ChemICare S.r.l., a start-up that develops SOCE modulators. The other authors declare that they do not have competing interests. (© 2021 The Authors. Published by American Chemical Society.)
Databáze:	MEDLINE
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