title: Spiropiperidine CCR5 antagonists.
abstract: A novel series of CCR5 antagonists has been identified, utilizing leads from high-throughput screening which were further modified based on insights from competitor molecules. Lead optimization was pursued by balancing opposing trends of metabolic stability and potency. Selective and potent analogs with good pharmacokinetic properties were successfully developed.
authors.affiliation: Roche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, CA 94304, USA. david.rotstein@roche.com
authors.forename: David M
authors.initials: DM
authors.lastname: Rotstein
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Gabriel
authors.forename: Ferenc
authors.initials: F
authors.lastname: Makra
authors.forename: Lubov
authors.initials: L
authors.lastname: Filonova
authors.forename: Shelley
authors.initials: S
authors.lastname: Gleason
authors.forename: Christine
authors.initials: C
authors.lastname: Brotherton-Pleiss
authors.forename: Lina Q
authors.initials: LQ
authors.lastname: Setti
authors.forename: Alejandra
authors.initials: A
authors.lastname: Trejo-Martin
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Lee
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: Paul
authors.initials: P
authors.lastname: Weller
authors.forename: Cheng-I
authors.initials: CI
authors.lastname: Mau
mesh_terms: D000818:Animals; D065100:CCR5 Receptor Antagonists; D018938:Caco-2 Cells; D004285:Dogs; D000882:Haplorhini; D006801:Humans; D010880:Piperidines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D019713:Receptors, CCR5 / Q000378:metabolism*; D013141:Spiro Compounds / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D065100:CCR5 Receptor Antagonists; D010880:Piperidines; D019713:Receptors, CCR5; D013141:Spiro Compounds