2-去甲白三烯类似物：白三烯C4、D4和E4气道及血管平滑肌效应的拮抗剂。

2-nor-leukotriene analogs: antagonists of the airway and vascular smooth muscle effects of leukotriene C4, D4 and E4.

作者信息

Gleason J G, Ku T W, McCarthy M E, Weichman B M, Holden D, Osborn R R, Zabko-Potapovich B, Berkowitz B, Wasserman M A

出版信息

Biochem Biophys Res Commun. 1983 Dec 28;117(3):732-9. doi: 10.1016/0006-291x(83)91658-3.

PMID:6320814

Abstract

A structural analog of LTD4, 4R-hydroxy-5S-cysteinylglycyl-6Z-nonadecenoic acid (4R, 5S, 6Z-2-nor-LTD1) has been synthesized and pharmacologically characterized. It significantly antagonized the contractile action of LTD4, LTC4 and LTE4 in guinea pig airways. In addition, this compound antagonized the in vitro vasoconstrictive effects of LTD4 in the guinea pig pulmonary artery. The study of a series of structural analogs of 4R, 5S, 6Z-2-nor-LTD1 suggests that the spatial separation of the C-1 (eicosanoid) carboxyl relative to the hydroxyl is a critical determinant in LTD4 agonist/antagonist activity.

摘要

白三烯D4（LTD4）的一种结构类似物，4R-羟基-5S-半胱氨酰甘氨酰-6Z-十九碳烯酸（4R，5S，6Z-2-去甲-LTD1）已被合成并进行了药理学表征。它能显著拮抗LTD4、白三烯C4（LTC4）和白三烯E4（LTE4）对豚鼠气道的收缩作用。此外，该化合物还能拮抗LTD4对豚鼠肺动脉的体外血管收缩作用。对一系列4R，5S，6Z-2-去甲-LTD1结构类似物的研究表明，C-1（类二十烷酸）羧基相对于羟基的空间分离是LTD4激动剂/拮抗剂活性的关键决定因素。