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ID: ALA1133796
Journal: Bioorg Med Chem Lett
Title: 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.
Authors: Finke PE, Meurer LC, Oates B, Mills SG, MacCoss M, Malkowitz L, Springer MS, Daugherty BL, Gould SL, DeMartino JA, Siciliano SJ, Carella A, Carver G, Holmes K, Danzeisen R, Hazuda D, Kessler J, Lineberger J, Miller M, Schleif WA, Emini EA.
Abstract: (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).
CiteXplore: 11206474