The discovery of structurally novel CCR1 antagonists derived from a hydroxyethylene peptide isostere template.
The present manuscript details the discovery and early fundamental structure-activity relationship studies involving compound 3, a novel hydroxyethylene peptide isostere derived molecule that provides micromolar inhibition of CCL3 binding to its receptor CCR1. Initial studies established this screening hit as a legitimate lead for further medicinal chemistry optimization.
Kath
John C
JC
Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA. john_c_kath@groton.pfizer.com
DiRico
Amy P
AP
Gladue
Ronald P
RP
Martin
William H
WH
McElroy
Eric B
EB
Stock
Ingrid A
IA
Tylaska
Laurie A
LA
Zheng
Deye
D
D018360:Crystallography, X-Ray; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation; D054389:Receptors, CCR1; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors*
D010455:Peptides; D054389:Receptors, CCR1; D019707:Receptors, Chemokine