title: CCR5 antagonists: 3-(pyrrolidin-1-yl)propionic acid analogues with potent anti-HIV activity.
abstract: [reaction: see text] A novel approach to alpha,alpha-disubstituted-beta-amino acids (beta(2,2)-amino acids) was employed in the synthesis of a series of 3-(pyrrolidin-1-yl)propionic acids possessing high affinity for the CCR5 receptor and potent anti-HIV activity. The rat pharmacokinetics for these new analogues featured higher bioavailabilities and lower rates of clearance as compared to cyclopentane 1.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, USA. christopher.lynch@abbott.com
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Lynch
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Hale
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Budhu
authors.forename: Amy L
authors.initials: AL
authors.lastname: Gentry
authors.forename: Paul E
authors.initials: PE
authors.lastname: Finke
authors.forename: Charles G
authors.initials: CG
authors.lastname: Caldwell
authors.forename: Sander G
authors.initials: SG
authors.lastname: Mills
authors.forename: Malcolm
authors.initials: M
authors.lastname: MacCoss
authors.forename: Dong-Ming
authors.initials: DM
authors.lastname: Shen
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
authors.initials: E
authors.lastname: Emini
mesh_terms: D019380:Anti-HIV Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D065100:CCR5 Receptor Antagonists; D011422:Propionates / Q000493:pharmacokinetics / Q000494:pharmacology*; D011759:Pyrrolidines / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: C478986:3-(pyrrolidin-1-yl)propionic acid; D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D011422:Propionates; D011759:Pyrrolidines