Synthesis and pharmacological characterization of novel inverse agonists acting on the viral-encoded chemokine receptor US28

…, SA Fratantoni, MJ Smit, IJP de Esch, R Leurs

Index: Hulshof, Janneke W.; Vischer, Henry F.; Verheij, Mark H.P.; Fratantoni, Silvina A.; Smit, Martine J.; de Esch, Iwan J.P.; Leurs, Rob Bioorganic and Medicinal Chemistry, 2006 , vol. 14, # 21 p. 7213 - 7230

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Citation Number: 36

Abstract

G-protein coupled receptors encoded by viruses represent an unexplored class of potential drug targets. In this study, we describe the synthesis and pharmacological characterization of the first class of inverse agonists acting on the HCMV-encoded receptor US28. It is shown that replacement of the 4-hydroxy group of lead compound 1 with a methylamine group results in a significant 6-fold increase in affinity. Interestingly, increasing the rigidity of the ...