Norborn-2-en-7-ones As Physiologically-triggered Carbon Monoxide-releasing Prodrugs

Overview

Journal Chem Sci

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2017 Oct 4

PMID 28970925

Citations 24

Authors

Jui Thiang Brian Kueh

Nathan J Stanley

Russell J Hewitt

Laura M Woods

Lesley Larsen

Joanne C Harrison

David Rennison

Margaret A Brimble

Ivan A Sammut

David S Larsen

Affiliations

Soon will be listed here.

Abstract

A prodrug strategy for the release of the gasotransmitter CO at physiological pH, based upon 3-bromo-norborn-2-en-7-one Diels-Alder cycloadducts of 2-bromomaleimides and 2,5-dimethyl-3,4-diphenylcyclopentadienone has been developed. Examples possessing protonated amine and diamine groups showed good water solubility and thermal stability. Half-lives for CO-release in TRIS-sucrose buffer at pH 7.4 ranged from 19 to 75 min at 37 °C and 31 to 32 h at 4 °C. Bioavailability in rats was demonstrated by oral gavage and showed a dose dependent vasorelaxant effect in pre-contracted rat aortic rings with an EC of 1.6 ± 0.9 μM. Increased intracellular CO levels following exposure were confirmed using a CO specific fluorescent probe.

Citing Articles

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