Novel highly potent OXE receptor antagonists with prolonged plasma lifetimes that are converted to active metabolites in vivo in monkeys.

ABSTRACT:

Background and purpose

The 5-lipoxygenase product 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-oxo-ETE), acting through the OXE receptor, is a potent eosinophil chemoattractant that may be an important proinflammatory mediator in eosinophilic diseases such as asthma. We previously identified a series of indole-based OXE receptor antagonists that rapidly appear in the blood following oral administration but have limited lifetimes. The objective of this study was to increase the potency and plasma half-lives of these compounds and thereby identify the optimal candidate for future preclinical studies in monkeys, as rodents do not have an OXE receptor orthologue.

Experimental approach

We synthesized a series of substituted phenylalkyl indoles and compared their antagonist potenc

SUBMITTER: Ye Q 

PROVIDER: S-EPMC6989946 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature