Discovery of small molecule benzimidazole antagonists of the chemokine receptor CXCR3.
High-throughput screening identified a low molecular weight antagonist of CXCR3 displaying micromolar activity in a membrane filtration-binding assay. Systematic modification of the benzimidazole core and tethered acetophenone moiety established tractable SAR of analogs with improved physicochemical properties and sub-micromolar activity across both human and murine receptors.
Hayes
Martin E
ME
Abbott Bioresearch Center, 381 Plantation Street, Worcester, MA 01605, USA. martin.hayes@abbott.com
Wallace
Grier A
GA
Grongsaard
Pintipa
P
Bischoff
Agnieszka
A
George
Dawn M
DM
Miao
Wenyan
W
McPherson
Michael J
MJ
Stoffel
Robert H
RH
Green
David W
DW
Roth
Gregory P
GP
D001562:Benzimidazoles / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D054367:Receptors, CXCR3 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D001562:Benzimidazoles; C515187:CXCR3 protein, human; C515188:Cxcr3 protein, mouse; D054367:Receptors, CXCR3