Synthesis and antiallergic activity of a novel series of 5-lipoxygenase inhibitors

K L Kees; J H Musser; J Chang; M Skowronek; A J Lewis

doi:10.1021/jm00161a031

Synthesis and antiallergic activity of a novel series of 5-lipoxygenase inhibitors

J Med Chem. 1986 Nov;29(11):2329-34. doi: 10.1021/jm00161a031.

Authors

K L Kees, J H Musser, J Chang, M Skowronek, A J Lewis

PMID: 2878078
DOI: 10.1021/jm00161a031

Abstract

A series of novel substituted [[(phenoxymethyl)phenyl]amino]oxoalkanoic acid esters have been synthesized. These compounds were tested in vitro for their ability to inhibit the synthesis of 5-hydroxyeicosatetraenoic acid and leukotriene (LT) B4 from rat polymorphonuclear leukocytes (PMN) and in vivo as inhibitors ovalbumin- (OA) and LTD4-induced bronchospasm in the guinea pig. Compounds 5-12 and 25 had IC50's between 1 and 5.6 microM in the rat PMN 5-lipoxygenase assay. Compounds 1, 3, and 16 inhibited OA-induced bronchoconstriction (61%, 64%, and 57%, respectively), but only 1 showed activity against LTD4-induced bronchoconstriction. When tested against LTD4-induced contraction of isolated guinea pig tracheal spiral strips, 1 was a competitive inhibitor with a pKB of 4.94.

MeSH terms

Animals
Arachidonate Lipoxygenases / antagonists & inhibitors*
Bronchi / drug effects
Guinea Pigs
Histamine H1 Antagonists / chemical synthesis*
Histamine H1 Antagonists / pharmacology
Hypersensitivity / drug therapy*
In Vitro Techniques
Lipoxygenase Inhibitors*
Male
SRS-A / antagonists & inhibitors

Substances

Histamine H1 Antagonists
Lipoxygenase Inhibitors
SRS-A
Arachidonate Lipoxygenases