Discovery of tetrahydroisoquinoline-based CXCR4 antagonists

…, D Culver, RF Arrendale, PR Gruddanti…

Index: Truax, Valarie M.; Zhao, Huanyu; Katzman, Brooke M.; Prosser, Anthony R.; Alcaraz, Ana A.; Saindane, Manohar T.; Howard, Randy B.; Culver, Deborah; Arrendale, Richard F.; Gruddanti, Prahbakar R.; Evers, Taylor J.; Natchus, Michael G.; Snyder, James P.; Liotta, Dennis C.; Wilson, Lawrence J. ACS Medicinal Chemistry Letters, 2013 , vol. 4, # 11 p. 1025 - 1030

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Citation Number: 12

Abstract

A de novo hit-to-lead effort involving the redesign of benzimidazole-containing antagonists of the CXCR4 receptor resulted in the discovery of a novel series of 1, 2, 3, 4- tetrahydroisoquinoline (TIQ) analogues. In general, this series of compounds show good potencies (3–650 nM) in assays involving CXCR4 function, including both inhibition of attachment of X4 HIV-1IIIB virus in MAGI-CCR5/CXCR4 cells and inhibition of calcium ...