Synthesis of some piperazine/piperidine amides of chromone-2-carboxylic acid as potential soluble epoxide hydrolase (sEH) inhibitors

Inhibition of soluble epoxide hydrolase (sEH) is implicated as a new therapeutic approach against inflammatory disorders in the context of metabolic and cardiovascular diseases. In the course of our ongoing research on sEH inhibitors, we synthesized novel piperididine/piperazine amide derivatives of...

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Bibliographic Details
Published in:Organic communications 2023-01, Vol.16 (1), p.24-34
Main Authors: Gur Maz, Tugce, Caliskan, Huseyin Burak
Format: Article
Language:English
Subjects:
Acids
Amides
Carboxylic acids
Cardiovascular diseases
Chromatography
Epoxide hydrolase
Inflammation
Inflammatory diseases
NMR
Nuclear magnetic resonance
Phosphatase
Piperazine
Piperidine
Staphylococcal enterotoxin H
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Summary:Inhibition of soluble epoxide hydrolase (sEH) is implicated as a new therapeutic approach against inflammatory disorders in the context of metabolic and cardiovascular diseases. In the course of our ongoing research on sEH inhibitors, we synthesized novel piperididine/piperazine amide derivatives of the chromone-2-carboxylic acid, and evaluated their inhibitory properties against human sEH. The chemical structures of the target compounds (2-5, 7-9) were elucidated by means of 1H-NMR, 13C-NMR and HRMS spectra. Initial screening of final compounds against sEH at a final concentration of 10 micromolar led to the identification of compound 7, which inhibited sEH activity in a concentration-dependent manner with an IC50 = 1.75 m​​​​​icromolar. Therefore, this chromen-2-amide derivative 7 decorated with benzyl piperidine on the amide side can be regarded as a novel lead structure, which pave the way of developing new analogues with improved inhibitory activities against sEH.
ISSN:1307-6175
1307-6175
DOI:10.25135/acg.oc.145.2302.2705