| Literature DB >> 31693857 |
Adeniyi Michael Adebesin1, Tim Wesser2, Jonnalagadda Vijaykumar1, Anne Konkel2, Mahesh P Paudyal1, Janine Lossie2, Chen Zhu1, Christina Westphal3, Narender Puli1, Robert Fischer2, Wolf-Hagen Schunck3, John R Falck1.
Abstract
17(R),18(S)-Epoxyeicosatetraenoic acid (EEQ) is a cytochrome P450 metabolite of eicosapentaenoic acid (EPA) and a powerful negative chronotrope with low nanomolar activity in a neonatal rat cardiomyocyte (NRCM) arrhythmia model. Prior studies identified oxamide 2b as a soluble epoxide hydrolase (sEH) stable replacement but unsuitable for in vivo applications due to limited oral bioavailability and metabolic stability. These ADME limitations have been addressed in an improved generation of negative chronotropes, e.g., 4 and 16, which were evaluated as potential clinical candidates.Entities:
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Year: 2019 PMID： 31693857 DOI： 10.1021/acs.jmedchem.9b00952
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446