1,3-Disubstituted and 1,3,3-trisubstituted adamantyl-ureas with isoxazole as soluble epoxide hydrolase inhibitors

Vladimir Burmistrov; Christophe Morisseau; Dmitry Danilov; Todd R. Harris; Igor Dalinger; Irina Vatsadze; Tatiana Shkineva; Gennady M. Butov; Bruce D. Hammock

doi:10.1016/j.bmcl.2015.10.066

1,3-Disubstituted and 1,3,3-trisubstituted adamantyl-ureas with isoxazole as soluble epoxide hydrolase inhibitors

Vladimir Burmistrov, Christophe Morisseau, Dmitry Danilov, Todd R. Harris, Igor Dalinger, Irina Vatsadze, Tatiana Shkineva, Gennady M. Butov, Bruce D. Hammock

Entomology

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

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	https://doi.org/10.1016/j.bmcl.2015.10.066
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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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 › peer-review

Burmistrov, Vladimir ; Morisseau, Christophe ; Danilov, Dmitry ; Harris, Todd R. ; Dalinger, Igor ; Vatsadze, Irina ; Shkineva, Tatiana ; Butov, Gennady M. ; Hammock, Bruce D. / 1,3-Disubstituted and 1,3,3-trisubstituted adamantyl-ureas with isoxazole as soluble epoxide hydrolase inhibitors. In: Bioorganic and Medicinal Chemistry Letters. 2015 ; Vol. 25, No. 23. pp. 5514-5519.

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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.",

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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.

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1,3-Disubstituted and 1,3,3-trisubstituted adamantyl-ureas with isoxazole as soluble epoxide hydrolase inhibitors

Abstract

Keywords

ASJC Scopus subject areas

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