title: 1,3,4 Trisubstituted pyrrolidine CCR5 receptor antagonists bearing 4-aminoheterocycle substituted piperidine side chains.
abstract: A new class of 4-(aminoheterocycle)piperidine derived 1,3,4 trisubstituted pyrrolidine CCR5 antagonists is reported. Compound 4a is shown to have good binding affinity (1.8 nM) and antiviral activity in PBMC's (IC(95)=50 nM). Compound 4a also has improved PK properties relative to 1.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. cwilloug@amgen.com
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Willoughby
authors.forename: Keith G
authors.initials: KG
authors.lastname: Rosauer
authors.forename: Jeffery J
authors.initials: JJ
authors.lastname: Hale
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Budhu
authors.forename: Sander G
authors.initials: SG
authors.lastname: Mills
authors.forename: Kevin T
authors.initials: KT
authors.lastname: Chapman
authors.forename: Malcolm
authors.initials: M
authors.lastname: MacCoss
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; D065100:CCR5 Receptor Antagonists; D016466:CHO Cells; D054407:Chemokine CCL4; D006224:Cricetinae; D006207:Half-Life; D006367:HeLa Cells; D006801:Humans; D006860:Hydrogen Bonding; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D010880:Piperidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats
chemical_list: D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D010880:Piperidines; D011759:Pyrrolidines