Norborn-2-en-7-ones as physiologically-triggered carbon monoxide-releasing prodrugs
| Autor: | Joanne C. Harrison, Ivan A. Sammut, Jui Thiang Brian Kueh, Russell J. Hewitt, David S. Larsen, Nathan J Stanley, Lesley Larsen, Margaret A. Brimble, Laura M. Woods, David Rennison |
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| Rok vydání: | 2017 |
| Předmět: |
Aqueous solution
010405 organic chemistry Protonation General Chemistry Prodrug 010402 general chemistry 01 natural sciences 0104 chemical sciences Bioavailability Chemistry chemistry.chemical_compound chemistry Diamine Organic chemistry Amine gas treating Thermal stability Carbon monoxide Nuclear chemistry |
| Zdroj: | Chemical Science |
| ISSN: | 2041-6539 2041-6520 |
| DOI: | 10.1039/c7sc01647f |
| Popis: | A prodrug strategy for the release of the gasotransmitter carbon monoxide (CO) at physiological pH, based upon 3a-bromo-norborn-2-en-7-one Diels–Alder cycloadducts has been developed. A prodrug strategy for the release of the gasotransmitter CO at physiological pH, based upon 3a-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 oCOm-21 showed a dose dependent vasorelaxant effect in pre-contracted rat aortic rings with an EC50 of 1.6 ± 0.9 μM. Increased intracellular CO levels following oCOm-21 exposure were confirmed using a CO specific fluorescent probe. |
| Databáze: | OpenAIRE |
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