title: Novel hexahydropyrrolo[3,4-c]pyrrole CCR5 antagonists.
abstract: Starting with a high-throughput screening lead, a novel series of CCR5 antagonists was developed utilizing an information-based approach. Improvement of pharmacokinetic properties for the series was pursued by SAR exploration of the lead template. The synthesis, SAR and biological profiles of the series are described.
authors.affiliation: Roche Palo Alto LLC, Palo Alto, CA 94304, USA. david.rotstein@comcast.net
authors.forename: David M
authors.initials: DM
authors.lastname: Rotstein
authors.forename: Chris R
authors.initials: CR
authors.lastname: Melville
authors.forename: Fernando
authors.initials: F
authors.lastname: Padilla
authors.forename: Dick
authors.initials: D
authors.lastname: Cournoyer
authors.forename: Eun K
authors.initials: EK
authors.lastname: Lee
authors.forename: Remy
authors.initials: R
authors.lastname: Lemoine
authors.forename: Ann C
authors.initials: AC
authors.lastname: Petersen
authors.forename: Lina Q
authors.initials: LQ
authors.lastname: Setti
authors.forename: Jutta
authors.initials: J
authors.lastname: Wanner
authors.forename: Lijing
authors.initials: L
authors.lastname: Chen
authors.forename: Lubov
authors.initials: L
authors.lastname: Filonova
authors.forename: David G
authors.initials: DG
authors.lastname: Loughhead
authors.forename: Jason
authors.initials: J
authors.lastname: Manka
authors.forename: Xiao-Fa
authors.initials: XF
authors.lastname: Lin
authors.forename: Shelley
authors.initials: S
authors.lastname: Gleason
authors.forename: Surya
authors.initials: S
authors.lastname: Sankuratri
authors.forename: Changhua
authors.initials: C
authors.lastname: Ji
authors.forename: Andre
authors.initials: A
authors.lastname: Derosier
authors.forename: Marianna
authors.initials: M
authors.lastname: Dioszegi
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Heilek
authors.forename: Andreas
authors.initials: A
authors.lastname: Jekle
authors.forename: Pamela
authors.initials: P
authors.lastname: Berry
authors.forename: Cheng-I
authors.initials: CI
authors.lastname: Mau
authors.forename: Paul
authors.initials: P
authors.lastname: Weller
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D065100:CCR5 Receptor Antagonists; D023581:HIV Fusion Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D019713:Receptors, CCR5 / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D001549:Benzamides; D065100:CCR5 Receptor Antagonists; D023581:HIV Fusion Inhibitors; D011758:Pyrroles; D019713:Receptors, CCR5