Use of receptor chimeras to identify small molecules with high affinity for the dynorphin A binding domain of the κ opioid receptor

…, D Guo, M Marella, JA Cassel, RN DeHaven…

Index: Kumar, Virendra; Guo, Deqi; Marella, Michael; Cassel, Joel A.; DeHaven, Robert N.; Daubert, Jeffrey D.; Mansson, Erik Bioorganic and Medicinal Chemistry Letters, 2008 , vol. 18, # 12 p. 3667 - 3671

Full Text: HTML

Citation Number: 3

Abstract

A series of 2-substituted sulfamoyl arylacetamides of general structure 2 were prepared as potent κ opioid receptor agonists and the affinities of these compounds for opioid and chimeric receptors were compared with those of dynorphin A. Compounds 2e and 2i were identified as non-peptide small molecules that bound to chimeras 3 and 4 with high affinities similar to dynorphin A, resulting in Ki values of 1.5 and 1.2 nM and 1.3 and 2.2 nM, ...