title: 1,3,4-Trisubstituted pyrrolidine CCR5 receptor antagonists: modifications of the arylpropylpiperidine side chains.
abstract: The 4-(3-phenylprop-1-yl)piperidine moiety of the 1,3,4-trisubstituted pyrrolidine CCR5 antagonist 1 was modified with electron deficient aromatics as well as replacement of the benzylic methylene with sulfones, gem-difluoromethylenes and alcohols in an effort to balance the antiviral potency with reasonable pharmacokinetics.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. chris_lynch@merck.com
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Lynch
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Willoughby
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Hale
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Holson
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Budhu
authors.forename: Amy L
authors.initials: AL
authors.lastname: Gentry
authors.forename: Keith G
authors.initials: KG
authors.lastname: Rosauer
authors.forename: Charles G
authors.initials: CG
authors.lastname: Caldwell
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Sander G
authors.initials: SG
authors.lastname: Mills
authors.forename: Malcolm
authors.initials: M
authors.lastname: MacCoss
authors.forename: Scott
authors.initials: S
authors.lastname: Berk
authors.forename: Liya
authors.initials: L
authors.lastname: Chen
authors.forename: Kevin T
authors.initials: KT
authors.lastname: Chapman
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: Salvatore J
authors.initials: SJ
authors.lastname: Siciliano
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Cascieri
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
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D065100:CCR5 Receptor Antagonists; D004285:Dogs; D006207:Half-Life; D006801:Humans; D007963:Leukocytes, Mononuclear; D008253:Macaca mulatta; D008657:Metabolic Clearance Rate; D010880:Piperidines / Q000737:chemistry; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D010880:Piperidines; D011759:Pyrrolidines; C032727:piperidine