(E)-3-[6-[[(2,6-dichlorophenyl)thio]methyl]-3-(2-phenylethoxy)-2-pyridinyl]-2-propenoic acid: A high-affinity leukotriene B-4 receptor antagonist with oral antiinflammatory activity

被引：14

作者：

Daines, RA ^{[1
]}

Chambers, PA ^{[1
]}

Foley, JJ ^{[1
]}

Griswold, DE ^{[1
]}

Kingsbury, WD ^{[1
]}

Martin, LD ^{[1
]}

Schmidt, DB ^{[1
]}

Sham, KKC ^{[1
]}

Sarau, HM ^{[1
]}

机构：

[1] SMITHKLINE BEECHAM PHARMACEUT,DEPT PHARMACOL,KING OF PRUSSIA,PA 19406

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1996年 / 39卷 / 19期

关键词：

D O I：

10.1021/jm960248s

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

An extensive structure-activity study based around the high-affinity leukotriene B-4 (LTB(4)) receptor antagonist SB 201146 (1) led to the identification of (E)-3-[6-[[(2,6-dichlorophenyl)thio]methyl]-3-(2-phenylethoxy)-2-pyridinyl]-2-propenoic acid (3). This compound displays high affinity for the human neutrophil LTB(4) receptor (K-i = 0.78 nM), blocks LTB(4)-induced Ca2+ mobilization with an IC50 of 6.6 +/- 1.5 nM, and demonstrates potent oral and topical antiinflammatory activity in a murine model of dermal inflammation.

引用

页码：3837 / 3841

页数：5

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