Abstract
Adamantyl ureas are good soluble epoxide hydrolase (sEH) inhibitors; however they have limited solubility and rapid metabolism, thus limiting their usefulness in some therapeutic indications. Herein, we test the hypothesis that nodal substitution on the adamantane will help solubilize and stabilize the compounds. A series of compounds containing adamantane derivatives and isoxazole functional groups were developed. Overall, the presence of methyl on the nodal positions of adamantane yields higher water solubility than previously reported urea-based sEH inhibitors while maintaining high inhibition potency. However, it did not improve microsomal stability.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 5514-5519 |
| Number of pages | 6 |
| Journal | Bioorganic and Medicinal Chemistry Letters |
| Volume | 25 |
| Issue number | 23 |
| DOIs | |
| State | Published - Dec 1 2015 |
Keywords
- Adamantane
- Inhibitor
- Isocyanate
- Isoxazole
- Soluble epoxide hydrolase
- Urea
ASJC Scopus subject areas
- Biochemistry
- Clinical Biochemistry
- Molecular Biology
- Molecular Medicine
- Organic Chemistry
- Drug Discovery
- Pharmaceutical Science
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Burmistrov, V., Morisseau, C., Danilov, D., Harris, T. R., Dalinger, I., Vatsadze, I., Shkineva, T., Butov, G. M., & Hammock, B. D. (2015). 1,3-Disubstituted and 1,3,3-trisubstituted adamantyl-ureas with isoxazole as soluble epoxide hydrolase inhibitors. Bioorganic and Medicinal Chemistry Letters, 25(23), 5514-5519. https://doi.org/10.1016/j.bmcl.2015.10.066