Format

Send to

Choose Destination
Eur J Med Chem. 2014 Apr 9;76:567-79. doi: 10.1016/j.ejmech.2014.02.041. Epub 2014 Feb 15.

New synthesis of 3-(β-D-glucopyranosyl)-5-substituted-1,2,4-triazoles, nanomolar inhibitors of glycogen phosphorylase.

Author information

1
Department of Organic Chemistry, University of Debrecen, POB 20, H-4010 Debrecen, Hungary.
2
Department of Medical Chemistry, Medical and Health Science Centre, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary.
3
Department of Organic Chemistry, University of Debrecen, POB 20, H-4010 Debrecen, Hungary. Electronic address: somsak@tigris.unideb.hu.

Abstract

O-Perbenzoylated 5-(β-D-glucopyranosyl)tetrazole was reacted with N-benzyl carboximidoyl chlorides to give the corresponding 4-benzyl-3-(β-D-glucopyranosyl)-5-substituted-1,2,4-triazoles. Removal of the O-benzoyl and N-benzyl protecting groups by base catalysed transesterification and catalytic hydrogenation, respectively, furnished a series of 3-(β-D-glucopyranosyl)-5-substituted-1,2,4-triazoles with aliphatic, mono- and bicyclic aromatic, and heterocyclic substituents in the 5-position. Enzyme kinetic studies revealed these compounds to inhibit rabbit muscle glycogen phosphorylase b: best inhibitors were the 5-(4-aminophenyl)- (Ki 0.67 μM) and the 5-(2-naphthyl)-substituted (Ki 0.41 μM) derivatives. This study uncovered the C-glucopyranosyl-1,2,4-triazoles as a novel skeleton for nanomolar inhibition of glycogen phosphorylase.

KEYWORDS:

1,2,4-Triazole; Bioisoster; C-glucopyranosyl derivative; Glycogen phosphorylase; Inhibitor

PMID:
24608000
DOI:
10.1016/j.ejmech.2014.02.041
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center