Novel 4, 4-disubstituted piperidine-based C–C chemokine receptor-5 inhibitors with high potency against human immunodeficiency virus-1 and an improved human …

…, C Aquino, BA Chauder, M Duan, R Ferris…

Index: Kazmierski, Wieslaw M.; Anderson, Don L.; Aquino, Christopher; Chauder, Brian A.; Duan, Maosheng; Ferris, Robert; Kenakin, Terrence; Koble, Cecilia S.; Lang, Dan G.; Mcintyre, Maggie S; Peckham, Jennifer; Watson, Christian; Wheelan, Pat; Spaltenstein, Andrew; Wire, Mary B.; Svolto, Angilique; Youngman, Michael Journal of Medicinal Chemistry, 2011 , vol. 54, # 11 p. 3756 - 3767

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Citation Number: 22

Abstract

We recently described (J. Med. Chem. 2008, 51, 6538− 6546) a novel class of CCR5 antagonists with strong anti-HIV potency. Herein, we detail SAR converting leads 1 and 2 to druglike molecules. The pivotal structural motif enabling this transition was the secondary sulfonamide substituent. Further fine-tuning of the substituent pattern in the sulfonamide paved the way to enhancing potency and bioavailability and minimizing hERG inhibition, ...