title: Synthesis and evaluation of CCR5 antagonists containing modified 4-piperidinyl-2-phenyl-1-(phenylsulfonylamino)-butane.
abstract: Synthesis of analogs containing more rigid bicyclic piperidine replacements for the 4-benzyloxycarbonyl-(ethyl)amino-piperidine moiety of the CCR5 antagonist structure, 1, is described. Although similar binding affinity to the lead was achieved with some analogs they were overall less potent anti-HIV agents suggesting that other features besides CCR5 binding are required for good anti-viral activity.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. shrenik_shah@merck.com
authors.forename: Shrenik K
authors.initials: SK
authors.lastname: Shah
authors.forename: Natalie
authors.initials: N
authors.lastname: Chen
authors.forename: Ravindra N
authors.initials: RN
authors.lastname: Guthikonda
authors.forename: Sander G
authors.initials: SG
authors.lastname: Mills
authors.forename: Lorraine
authors.initials: L
authors.lastname: Malkowitz
authors.forename: Martin S
authors.initials: MS
authors.lastname: Springer
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Gould
authors.forename: Julie A
authors.initials: JA
authors.lastname: Demartino
authors.forename: Anthony
authors.initials: A
authors.lastname: Carella
authors.forename: Gwen
authors.initials: G
authors.lastname: Carver
authors.forename: Karen
authors.initials: K
authors.lastname: Holmes
authors.forename: William A
authors.initials: WA
authors.lastname: Schleif
authors.forename: Renee
authors.initials: R
authors.lastname: Danzeisen
authors.forename: Daria
authors.initials: D
authors.lastname: Hazuda
authors.forename: Joseph
authors.initials: J
authors.lastname: Kessler
authors.forename: Janet
authors.initials: J
authors.lastname: Lineberger
authors.forename: Michael
authors.initials: M
authors.lastname: Miller
authors.forename: Emilio A
authors.initials: EA
authors.lastname: Emini
authors.forename: Malcolm
authors.initials: M
authors.lastname: MacCoss
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002073:Butanes / Q000138:chemical synthesis / Q000494:pharmacology; D065100:CCR5 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D020128:Inhibitory Concentration 50; D010880:Piperidines / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis* / Q000494:pharmacology; D014780:Viruses / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D002073:Butanes; D065100:CCR5 Receptor Antagonists; D010880:Piperidines; D013450:Sulfones