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 |
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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
Cite this
1,3-Disubstituted and 1,3,3-trisubstituted adamantyl-ureas with isoxazole as soluble epoxide hydrolase inhibitors. / Burmistrov, Vladimir; Morisseau, Christophe; Danilov, Dmitry; Harris, Todd R.; Dalinger, Igor; Vatsadze, Irina; Shkineva, Tatiana; Butov, Gennady M.; Hammock, Bruce D.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 25, No. 23, 01.12.2015, p. 5514-5519.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 1,3-Disubstituted and 1,3,3-trisubstituted adamantyl-ureas with isoxazole as soluble epoxide hydrolase inhibitors
AU - Burmistrov, Vladimir
AU - Morisseau, Christophe
AU - Danilov, Dmitry
AU - Harris, Todd R.
AU - Dalinger, Igor
AU - Vatsadze, Irina
AU - Shkineva, Tatiana
AU - Butov, Gennady M.
AU - Hammock, Bruce D.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - 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.
AB - 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.
KW - Adamantane
KW - Inhibitor
KW - Isocyanate
KW - Isoxazole
KW - Soluble epoxide hydrolase
KW - Urea
UR - http://www.scopus.com/inward/record.url?scp=84946723450&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84946723450&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2015.10.066
DO - 10.1016/j.bmcl.2015.10.066
M3 - Article
C2 - 26520661
AN - SCOPUS:84946723450
VL - 25
SP - 5514
EP - 5519
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 23
ER -