title: From rigid cyclic templates to conformationally stabilized acyclic scaffolds. Part II: Acyclic replacements for the (3S)-3-benzylpiperidine in a series of potent CCR3 antagonists.
abstract: Conformational analysis of the 3-benzylpiperidine in CCR3 antagonist clinical candidate 1 (BMS-639623) predicts that the benzylpiperidine may be replaced by acyclic, conformationally stabilized, anti-1,2-disubstituted phenethyl- and phenpropylamines. Ab initio calculations, enantioselective syntheses, and evaluation in CCR3 binding and chemotaxis assays of anti-1-methyl-2-hydroxyphenethyl- and phenpropylamine-containing CCR3 antagonists support this conformational correlation.
authors.affiliation: Bristol-Myers Squibb Company, R & D, PO Box 4000, Princeton, NJ 08543-4000, USA.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Gardner
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Santella
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Tebben
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Batt
authors.forename: Soo S
authors.initials: SS
authors.lastname: Ko
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Traeger
authors.forename: Patricia K
authors.initials: PK
authors.lastname: Welch
authors.forename: Eric A
authors.initials: EA
authors.lastname: Wadman
authors.forename: Paul
authors.initials: P
authors.lastname: Davies
authors.forename: Percy H
authors.initials: PH
authors.lastname: Carter
authors.forename: John V
authors.initials: JV
authors.lastname: Duncia
mesh_terms: D003500:Cyclization; D006860:Hydrogen Bonding; D008968:Molecular Conformation; D010880:Piperidines / Q000737:chemistry* / Q000494:pharmacology*; D054397:Receptors, CCR3 / Q000037:antagonists & inhibitors*; D014508:Urea / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
chemical_list: C528978:BMS-639623; C515350:CCR3 protein, human; D010880:Piperidines; D054397:Receptors, CCR3; D014508:Urea