CCR3拮抗剂：一种治疗哮喘的潜在新疗法。发现与构效关系。

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

作者信息

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

机构信息

Bristol-Myers Squibb Company, Experimental Station, PO Box 80336, Wilmington, DE 19880-0336, USA.

出版信息

Bioorg Med Chem Lett. 2002 Jul 8;12(13):1785-9. doi: 10.1016/s0960-894x(02)00206-8.

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

PMID:12067561

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.

摘要

CCR3拮抗剂中，那些IC(50)值在微摩尔范围内的被转化为低纳摩尔结合化合物，这些化合物在体外对人嗜酸性粒细胞趋化因子诱导的人嗜酸性粒细胞趋化作用具有抑制作用。特别地，4-苄基哌啶-1-基-正丙基脲和赤式-3-(4-苄基-2-(α-羟烷基)哌啶-1-基)-正丙基脲（通过N-BOC-4-苄基哌啶的Beak反应获得）对CCR3表现出个位数纳摩尔的IC(50)值。