title: Antagonists of the human CCR5 receptor as anti-HIV-1 agents. Part 3: a proposed pharmacophore model for 1-[N-(methyl)-N-(phenylsulfonyl)amino]-2-(phenyl)-4-[4-(substituted)piperidin-1-yl]butanes.
abstract: Structure-activity relationship studies directed toward the optimization of (2S)-2-(3-chlorophenyl)-1-[N-(methyl)-N-(phenylsulfonyl)amino]-4-[4-(substituted)piperidin-1-yl]butanes as CCR5 antagonists resulted in the synthesis of the spiro-indanone derivative 8c (IC50=5 nM). These and previous results are summarized in a proposed pharmacophore model for this class of CCR5 antagonist.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. paul_finke@merck.com
authors.forename: P E
authors.initials: PE
authors.lastname: Finke
authors.forename: L C
authors.initials: LC
authors.lastname: Meurer
authors.forename: B
authors.initials: B
authors.lastname: Oates
authors.forename: S K
authors.initials: SK
authors.lastname: Shah
authors.forename: J L
authors.initials: JL
authors.lastname: Loebach
authors.forename: S G
authors.initials: SG
authors.lastname: Mills
authors.forename: M
authors.initials: M
authors.lastname: MacCoss
authors.forename: L
authors.initials: L
authors.lastname: Castonguay
authors.forename: L
authors.initials: L
authors.lastname: Malkowitz
authors.forename: M S
authors.initials: MS
authors.lastname: Springer
authors.forename: S L
authors.initials: SL
authors.lastname: Gould
authors.forename: J A
authors.initials: JA
authors.lastname: DeMartino
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D002073:Butanes / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D065100:CCR5 Receptor Antagonists; D002478:Cells, Cultured; D054407:Chemokine CCL4; D006224:Cricetinae; D006801:Humans; D020128:Inhibitory Concentration 50; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D009504:Neutrophils / Q000187:drug effects / Q000821:virology; D010880:Piperidines / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D002073:Butanes; D065100:CCR5 Receptor Antagonists; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D010880:Piperidines; C032727:piperidine