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

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

Journal

Bioorganic & Medicinal Chemistry Letters
ISSN: 1464-3405 , E-ISSN: 0960-894X

Output data

Year: 2015, Volume: 25, Number: 23, Pages: 5514-5519 Pages count : 6 DOI: 10.1016/j.bmcl.2015.10.066

Authors

Burmistrov Vladimir ^1,2 , Morisseau Christophe ¹ , Danilov Dmitry ² , Harris Todd R. ¹ , Dalinger Igor ³ , Vatsadze Irina ³ , Shkineva Tatiana ³ , Butov Gennady M. ² , Hammock Bruce D. ¹

Affiliations

1	Department of Entomology and Nematology, and UC Davis Comprehensive Cancer Center, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA
2	Department of Chemistry, Technology and Equipment of Chemical Industry, Volzhsky Polytechnic Institute (Branch) Volgograd State Technical University, Volzhsky, Russia
3	N.D. Zelinsky Institute of Organic Chemistry (ZIOC) of Russian Academy of Sciences, Moscow, Russia

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.

Burmistrov V. , Morisseau C. , Danilov D. , Harris T.R. , Dalinger I. , Vatsadze I. , Shkineva T. , Butov G.M. , Hammock B.D.
1,3-Disubstituted and 1,3,3-trisubstituted adamantyl-ureas with isoxazole as soluble epoxide hydrolase inhibitors
Bioorganic & Medicinal Chemistry Letters. 2015. V.25. N23. P.5514-5519. DOI: 10.1016/j.bmcl.2015.10.066 WOS Scopus OpenAlex

≡ Web of science:	WOS:000364535400011
≡ Scopus:	2-s2.0-84946723450
≡ OpenAlex:	W1938599872