Lead identification of 2-iminobenzimidazole antagonists of the chemokine receptor CXCR3.
Modification of a 2-iminobenzimidazole series derived from an HTS hit resulted in compounds with improved in-vitro species selectivity. Incorporation of an 8-quinoline amide and conformational rigidification of an aliphatic tether furnished potent compounds suitable for further lead optimization.
Hayes
Martin E
ME
Abbott Bioresearch Center, Medicinal Chemistry, 381 Plantation Street, Worcester, MA 01605, USA. martin.hayes@abbott.com
Breinlinger
Eric C
EC
Wallace
Grier A
GA
Grongsaard
Pintipa
P
Miao
Wenyan
W
McPherson
Michael J
MJ
Stoffel
Robert H
RH
Green
David W
DW
Roth
Gregory P
GP
D000577:Amides / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D001665:Binding Sites; D016466:CHO Cells / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D008956:Models, Chemical; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology*; D011869:Radioligand Assay; D054367:Receptors, CXCR3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
D000577:Amides; D001562:Benzimidazoles; D011804:Quinolines; D054367:Receptors, CXCR3