(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
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
收藏
页码:3837 / 3841
页数:5
相关论文
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