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ID: ALA1150399

Journal: Bioorg Med Chem

Title: Evaluation of novel hyphodermin derivatives as glycogen phosphorylase a inhibitors.

Authors: Loughlin WA, Pierens GK, Petersson MJ, Henderson LC, Healy PC.

Abstract: The lipophilicity, permeability, solubility, polar surface area and 'rule-of-five' properties were assessed, using QikProp v2.5 (Schrödinger, Inc.) and ALOGPS 2.1 calculations, for 25 Hyphodermin derivatives. These compounds obeyed the 'rule-of-five', and the calculated physicochemical values were generally within desired limits. All compounds were tested against Glycogen Phosphorylase a (GPa). Four phenyl and benzyl substituted 2-oxo-hexahydro and tetrahydrobenzo[cd]indole carboxylic acids were identified as novel inhibitors of GPa with estimated IC(50) values in the range 0.8-1.3mM. Molecular modelling of these novel inhibitors was used to obtain the main structural features of this class of molecule for future structure-activity relationship studies.

CiteXplore: 18485716

DOI: 10.1016/j.bmc.2008.04.047