title: CCR2B receptor antagonists: conversion of a weak HTS hit to a potent lead compound.
abstract: A weak HTS hit at the CCR2B receptor has been converted into a potent antagonist by array SAR studies. Selectivity over the closely related CCR5 receptor is also achieved.
authors.affiliation: Department of Discovery Chemistry, SmithKline Beecham Pharmaceuticals, Harlow, Essex, UK. ian_t_forbes@sbphrd.com
authors.forename: I T
authors.initials: IT
authors.lastname: Forbes
authors.forename: D G
authors.initials: DG
authors.lastname: Cooper
authors.forename: E K
authors.initials: EK
authors.lastname: Dodds
authors.forename: D M
authors.initials: DM
authors.lastname: Hickey
authors.forename: R J
authors.initials: RJ
authors.lastname: Ife
authors.forename: M
authors.initials: M
authors.lastname: Meeson
authors.forename: M
authors.initials: M
authors.lastname: Stockley
authors.forename: T A
authors.initials: TA
authors.lastname: Berkhout
authors.forename: J
authors.initials: J
authors.lastname: Gohil
authors.forename: P H
authors.initials: PH
authors.lastname: Groot
authors.forename: K
authors.initials: K
authors.lastname: Moores
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D018932:Chemokine CCL2 / Q000737:chemistry / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008024:Ligands; D015394:Molecular Structure; D009000:Monocytes / Q000187:drug effects; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C418102:3-(1-(((3-(3,4-dichlorophenyl)propenoyl)amino)pentyl)piperidin-4-yl)-5-hydroxyindole; D000577:Amides; C515334:CCR2 protein, human; D018932:Chemokine CCL2; D007211:Indoles; D008024:Ligands; D010880:Piperidines; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine