title: CCR5 antagonists: bicyclic isoxazolidines as conformationally constrained N-1-substituted pyrrolidines.
abstract: A series of CCR5 antagonists containing bicyclic isoxazolidines was generated through a nitrone mediated cycloaddition with olefins bearing the preferred pharmacophores previously described. Potent antagonists (3 and 16) were generated with enhanced affinity for the CCR5 receptor while maintaining antiviral activity against HIV.
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: Amy L
authors.initials: AL
authors.lastname: Gentry
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Hale
authors.forename: Sander G
authors.initials: SG
authors.lastname: Mills
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: George
authors.initials: G
authors.lastname: Doss
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: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D065100:CCR5 Receptor Antagonists; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D011485:Protein Binding; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D065100:CCR5 Receptor Antagonists; D007555:Isoxazoles; D011759:Pyrrolidines