title: Syntheses and SAR studies of 4-(heteroarylpiperdin-1-yl-methyl)-pyrrolidin-1-yl-acetic acid antagonists of the human CCR5 chemokine receptor.
abstract: Efforts toward the exploration of the title compounds as CCR5 antagonists are disclosed. The basis for such work stems from the fact that cellular proliferation of HIV-1 requires the cooperative assistance of both CCR5 and CD4 receptors. The synthesis and SAR of pyrrolidineacetic acid derivatives as CCR5 antagonists displaying potent binding and antiviral properties in a HeLa cell-based HIV-1 infectivity assay are discussed.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. kothandaraman_shankaran@merck.com
authors.forename: K
authors.initials: K
authors.lastname: Shankaran
authors.forename: Karla L
authors.initials: KL
authors.lastname: Donnelly
authors.forename: Shrenik K
authors.initials: SK
authors.lastname: Shah
authors.forename: Ravindra N
authors.initials: RN
authors.lastname: Guthikonda
authors.forename: Malcolm
authors.initials: M
authors.lastname: MacCoss
authors.forename: Sander G
authors.initials: SG
authors.lastname: Mills
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Gould
authors.forename: Lorraine
authors.initials: L
authors.lastname: Malkowitz
authors.forename: Salvatore J
authors.initials: SJ
authors.lastname: Siciliano
authors.forename: Martin S
authors.initials: MS
authors.lastname: Springer
authors.forename: Anthony
authors.initials: A
authors.lastname: Carella
authors.forename: Gwen
authors.initials: G
authors.lastname: Carver
authors.forename: Daria
authors.initials: D
authors.lastname: Hazuda
authors.forename: Karen
authors.initials: K
authors.lastname: Holmes
authors.forename: Joseph
authors.initials: J
authors.lastname: Kessler
authors.forename: Janet
authors.initials: J
authors.lastname: Lineberger
authors.forename: Michael D
authors.initials: MD
authors.lastname: Miller
authors.forename: Emilio A
authors.initials: EA
authors.lastname: Emini
authors.forename: William A
authors.initials: WA
authors.lastname: Schleif
mesh_terms: D000085:Acetates / Q000737:chemistry; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001665:Binding Sites; D065100:CCR5 Receptor Antagonists; D002455:Cell Division / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D010880:Piperidines / Q000138:chemical synthesis / Q000494:pharmacology; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000085:Acetates; D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D010880:Piperidines; D011759:Pyrrolidines