CCR3 antagonists: a potential new therapy for the treatment of asthma. Discovery and structure-activity relationships.

Dean A Wacker, Joseph B Santella, Daniel S Gardner, Jeffrey G Varnes, Melissa Estrella, George V DeLucca, Soo S Ko, Keiichi Tanabe, Paul S Watson, Patricia K Welch, Maryanne Covington, Nicole C Stowell, Eric A Wadman, Paul Davies, Kimberly A Solomon, Robert C Newton, George L Trainor, Steven M Friedman, Carl P Decicco, John V Duncia

Journal: Bioorganic & medicinal chemistry letters 2002;12(13):1785-9

PMID: 12067561

Full Text on Elsevier Science View on PubMed

Abstract

CCR3 antagonist leads with IC(50) values in the microM range were converted into low nM binding compounds that displayed in vitro inhibition of human eosinophil chemotaxis induced by human eotaxin. In particular, 4-benzylpiperidin-1-yl-n-propylureas and erythro-3-(4-benzyl-2-(alpha-hydroxyalkyl)piperidin-1-yl)-n-propylureas (obtained via Beak reaction of N-BOC-4-benzylpiperidine) exhibited single digit nanomolar IC(50) values for CCR3.

Address: Bristol-Myers Squibb Company, Experimental Station, PO Box 80336, Wilmington, DE 19880-0336, USA. [email protected]

DOI: 10.1016/s0960-894x(02)00206-8

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MeSH Terms: Alkylation, Amides, Anti-Asthmatic Agents, Calcium, Chemokine CCL11, Chemokines, CC, Chemotaxis, Leukocyte, Humans, Inhibitory Concentration 50, Ligands, Piperidines, Receptors, CCR3, Receptors, Chemokine, Stereoisomerism, Structure-Activity Relationship