Antagonists of the human CCR5 receptor as anti-HIV-1 agents.: Part 2:: Structure-activity relationships for substituted 2-aryl-1-[N-(methyl)-N-(phenylsulfonyl) amino]-4-(piperidin-1-yl)butanes

(2S)-2-(3,4-Dichlorophenyl)-1-[N-(methyl)-N-(phenylsulfonyl)amino]-4-[spiro(2,3-dihydrobenzthiophene-3,4'-piperidin-1'-yl)]butane S-oxide (3) has been identified as a potent CCR5 antagonist lead structure having an IC50 = 35 nM. Herein, we describe the structure-activity relationship studies directed toward the requirement for and optimization of the C-2 phenyl fragment. The phenyl was found to be important for CCR5 antagonism and substitution was limited to small moieties at the 3-position (13 and 16. X=H, 3-F, 3-Cl, 3-Me). (C) 2001 Published by Elsevier Science Ltd.