Novel Thienopyrrole Glycogen Phosphorylase Inhibitors: Synthesis, in Vitro SAR and Crystallographic Studies

Overview

Journal Bioorg Med Chem Lett

Specialty Biochemistry

Date 2006 Sep 2

PMID 16945526

Citations 8

Authors

Paul R O Whittamore

Matthew S Addie

Stuart N L Bennett

Alan M Birch

Michael Butters

Linda Godfrey

Peter W Kenny

Andrew D Morley

Paul M Murray

Nikos G Oikonomakos

Ludovic R Otterbein

Andrew D Pannifer

Jeremy S Parker

Kristy Readman

Pawel S Siedlecki

Paul Schofield

Andy Stocker

Melvyn J Taylor

Linda A Townsend

David P Whalley

Jennifer Whitehouse

Affiliations

Soon will be listed here.

Abstract

Two series of novel thienopyrrole inhibitors of recombinant human liver glycogen phosphorylase a (GPa) which are effective in reducing glucose output from rat hepatocytes are described. Representative compounds have been shown to bind at the dimer interface site of the rabbit muscle enzyme by X-ray crystallography.

Citing Articles

2-Thiazolo[4,5-][1,2,3]triazole: synthesis, functionalization, and application in scaffold-hopping.

Miyazaki R, Takada F, Kikuchi T, Oguro Y, Kamata M, Yukawa T Chem Sci. 2024; .

PMID: 39282646 PMC: 11391401. DOI: 10.1039/d4sc03874f.

Novel pyrazolothienopyridinones as potential GABA receptor modulators.

Vega Alanis B, Wimmer L, Ernst M, Schnurch M, Mihovilovic M Monatsh Chem. 2023; 154(12):1427-1439.

PMID: 38020488 PMC: 10667146. DOI: 10.1007/s00706-023-03063-6.

Discovery and Biotechnological Exploitation of Glycoside-Phosphorylases.

Li A, Benkoulouche M, Ladeveze S, Durand J, Cioci G, Laville E Int J Mol Sci. 2022; 23(6).

PMID: 35328479 PMC: 8950772. DOI: 10.3390/ijms23063043.

Glycogen phosphorylase revisited: extending the resolution of the R- and T-state structures of the free enzyme and in complex with allosteric activators.

Leonidas D, Zographos S, Tsitsanou K, Skamnaki V, Stravodimos G, Kyriakis E Acta Crystallogr F Struct Biol Commun. 2021; 77(Pt 9):303-311.

PMID: 34473107 PMC: 8411930. DOI: 10.1107/S2053230X21008542.

Discovering protein-ligand chalcogen bonding in the protein data bank using endocyclic sulfur-containing heterocycles as ligand search subsets.

Mitchell M J Mol Model. 2017; 23(10):287.

PMID: 28942498 DOI: 10.1007/s00894-017-3452-3.