The synthesis, biological activity, and pharmacokinetic profile of CCR1 antagonists are described.
View Article and Find Full Text PDFThe synthesis, biological activity, and pharmacokinetic profile of novel CCR1 antagonists are described.
View Article and Find Full Text PDFThe present manuscript details structure-activity relationship studies of lead structure 1, which led to the discovery of CCR1 antagonists >100-fold more potent than 1.
View Article and Find Full Text PDFThe 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.
View Article and Find Full Text PDFThe chemokines CCL3 and CCL5, as well as their shared receptor CCR1, are believed to play a role in the pathogenesis of several inflammatory diseases including rheumatoid arthritis, multiple sclerosis, and transplant rejection. In this study we describe the pharmacological properties of a novel small molecular weight CCR1 antagonist, CP-481,715 (quinoxaline-2-carboxylic acid [4(R)-carbamoyl-1(S)-(3-fluorobenzyl)-2(S),7-dihydroxy-7-methyloctyl]amide). Radiolabeled binding studies indicate that CP-481,715 binds to human CCR1 with a Kd of 9.
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