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

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

doi:10.1016/0006-291x(83)91658-3

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

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

Authors

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

PMID: 6320814
DOI: 10.1016/0006-291x(83)91658-3

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.

Publication types

Comparative Study

MeSH terms

Airway Resistance / drug effects*
Animals
Guinea Pigs
In Vitro Techniques
Leukotriene E4
Muscle Contraction / drug effects
Muscle, Smooth, Vascular / drug effects*
SRS-A / analogs & derivatives*
SRS-A / antagonists & inhibitors*
SRS-A / pharmacology
Structure-Activity Relationship

Substances

SRS-A
Leukotriene E4