4(5)-Aryl-2-C-glucopyranosyl-imidazoles as New Nanomolar Glucose Analogue Inhibitors of Glycogen Phosphorylase

Éva Bokor; Sándor Kun; Tibor Docsa; Pál Gergely; László Somsák

doi:10.1021/acsmedchemlett.5b00361

4(5)-Aryl-2-C-glucopyranosyl-imidazoles as New Nanomolar Glucose Analogue Inhibitors of Glycogen Phosphorylase

ACS Med Chem Lett. 2015 Oct 19;6(12):1215-9. doi: 10.1021/acsmedchemlett.5b00361. eCollection 2015 Dec 10.

Authors

Éva Bokor¹, Sándor Kun¹, Tibor Docsa², Pál Gergely², László Somsák¹

Affiliations

¹ Department of Organic Chemistry, University of Debrecen , POB 20, H-4010 Debrecen, Hungary.
² Department of Medical Chemistry, Faculty of Medicine, University of Debrecen , Egyetem tér 1, H-4032 Debrecen, Hungary.

Abstract

Inhibition of glycogen phosphorylases may lead to pharmacological treatments of diseases in which glycogen metabolism plays an important role: first of all in diabetes, but also in cardiovascular and tumorous disorders. C-(β-d-Glucopyranosyl) isoxazole, pyrazole, thiazole, and imidazole type compounds were synthesized, and the latter showed the strongest inhibition against rabbit muscle glycogen phosphorylase b. Most efficient was 2-(β-d-glucopyranosyl)-4(5)-(2-naphthyl)-imidazole (11b, K i = 31 nM) representing the best nanomolar glucose derived inhibitor of the enzyme.

Keywords: C-Glucopyranosyl derivative; glycogen phosphorylase; imidazole; inhibitor; isoxazole; pyrazole; thiazole.