CCR2B receptor antagonists: conversion of a weak HTS hit to a potent lead compound.
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.
Forbes
I T
IT
Department of Discovery Chemistry, SmithKline Beecham Pharmaceuticals, Harlow, Essex, UK. ian_t_forbes@sbphrd.com
Cooper
D G
DG
Dodds
E K
EK
Hickey
D M
DM
Ife
R J
RJ
Meeson
M
M
Stockley
M
M
Berkhout
T A
TA
Gohil
J
J
Groot
P H
PH
Moores
K
K
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
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