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=35nM. 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).