title: Evaluation of amide replacements in CCR5 antagonists as a means to increase intrinsic permeability. Part 2: SAR optimization and pharmacokinetic profile of a homologous azacyle series.
abstract: Replacement of a secondary amide with a piperidine or azetidine moiety in a series of CCR5 antagonists led to the discovery of compounds with increased intrinsic permeability. This effort led to the identification of a potent CCR5 antagonist which exhibited an improved in vivo pharmacokinetic profile.
authors.affiliation: Department of Medicinal Chemistry, Roche Palo Alto, 3431 Hillview Avenue, Palo Alto, CA 94304, USA. jutta.wanner@roche.com
authors.forename: Jutta
authors.initials: J
authors.lastname: Wanner
authors.forename: Lijing
authors.initials: L
authors.lastname: Chen
authors.forename: Rémy C
authors.initials: RC
authors.lastname: Lemoine
authors.forename: Rama
authors.initials: R
authors.lastname: Kondru
authors.forename: Andreas
authors.initials: A
authors.lastname: Jekle
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Heilek
authors.forename: André
authors.initials: A
authors.lastname: deRosier
authors.forename: Changhua
authors.initials: C
authors.lastname: Ji
authors.forename: Pamela W
authors.initials: PW
authors.lastname: Berry
authors.forename: David M
authors.initials: DM
authors.lastname: Rotstein
mesh_terms: D000577:Amides / Q000737:chemistry*; D001372:Aza Compounds / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D065100:CCR5 Receptor Antagonists; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D001372:Aza Compounds; D065100:CCR5 Receptor Antagonists