title: 1,3,4-Trisubstituted pyrrolidine CCR5 receptor antagonists. Part 2: lead optimization affording selective, orally bioavailable compounds with potent anti-HIV activity.
abstract: Investigations of the structure-activity relationships of 1,3,4-trisubstituted pyrrolidine human CCR5 receptor antagonists afforded orally bioavailable compounds with the ability to inhibit HIV replication in vitro.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. jeffrey_hale@merck.com
authors.forename: J J
authors.initials: JJ
authors.lastname: Hale
authors.forename: R J
authors.initials: RJ
authors.lastname: Budhu
authors.forename: E B
authors.initials: EB
authors.lastname: Holson
authors.forename: P E
authors.initials: PE
authors.lastname: Finke
authors.forename: B
authors.initials: B
authors.lastname: Oates
authors.forename: S G
authors.initials: SG
authors.lastname: Mills
authors.forename: M
authors.initials: M
authors.lastname: MacCoss
authors.forename: S L
authors.initials: SL
authors.lastname: Gould
authors.forename: J A
authors.initials: JA
authors.lastname: DeMartino
authors.forename: M S
authors.initials: MS
authors.lastname: Springer
authors.forename: S
authors.initials: S
authors.lastname: Siciliano
authors.forename: L
authors.initials: L
authors.lastname: Malkowitz
authors.forename: W A
authors.initials: WA
authors.lastname: Schleif
authors.forename: D
authors.initials: D
authors.lastname: Hazuda
authors.forename: M
authors.initials: M
authors.lastname: Miller
authors.forename: J
authors.initials: J
authors.lastname: Kessler
authors.forename: R
authors.initials: R
authors.lastname: Danzeisen
authors.forename: K
authors.initials: K
authors.lastname: Holmes
authors.forename: J
authors.initials: J
authors.lastname: Lineberger
authors.forename: A
authors.initials: A
authors.lastname: Carella
authors.forename: G
authors.initials: G
authors.lastname: Carver
authors.forename: E
authors.initials: E
authors.lastname: Emini
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D065100:CCR5 Receptor Antagonists; D016466:CHO Cells; D006224:Cricetinae; D006678:HIV / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D011759:Pyrrolidines