title: Antagonists of the human CCR5 receptor as anti-HIV-1 agents. Part 4: synthesis and structure-activity relationships for 1-[N-(methyl)-N-(phenylsulfonyl)amino]-2-(phenyl)-4-(4-(N-(alkyl)-N-(benzyloxycarbonyl)amino)piperidin-1-yl)butanes.
abstract: (2S)-2-(3-Chlorophenyl)-1-[N-(methyl)-N-(phenylsulfonyl)amino]-4-[spiro(2,3-dihydrobenzthiophene-3,4'-piperidin-1'-yl)]butane S-oxide (1b) has been identified as a potent CCR5 antagonist having an IC50=10 nM. Herein, structure-activity relationship studies of non-spiro piperidines are described, which led to the discovery of 4-(N-(alkyl)-N-(benzyloxycarbonyl)amino)piperidine derivatives (3-5) as potent CCR5 antagonists.
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: B
authors.initials: B
authors.lastname: Oates
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: 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
authors.forename: A
authors.initials: A
authors.lastname: Carella
authors.forename: G
authors.initials: G
authors.lastname: Carver
authors.forename: K
authors.initials: K
authors.lastname: Holmes
authors.forename: R
authors.initials: R
authors.lastname: Danzeisen
authors.forename: D
authors.initials: D
authors.lastname: Hazuda
authors.forename: J
authors.initials: J
authors.lastname: Kessler
authors.forename: J
authors.initials: J
authors.lastname: Lineberger
authors.forename: M
authors.initials: M
authors.lastname: Miller
authors.forename: W A
authors.initials: WA
authors.lastname: Schleif
authors.forename: E A
authors.initials: EA
authors.lastname: Emini
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology*; D002073:Butanes / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*; D065100:CCR5 Receptor Antagonists; D002478:Cells, Cultured; D006224:Cricetinae; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D009504:Neutrophils / Q000187:drug effects / Q000821:virology; D010880:Piperidines / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D002073:Butanes; D065100:CCR5 Receptor Antagonists; D010880:Piperidines