Takai_2015_Bioorg.Med.Chem.Lett_25_1705

Reference

Title : Three-dimensional rational approach to the discovery of potent substituted cyclopropyl urea soluble epoxide hydrolase inhibitors - Takai_2015_Bioorg.Med.Chem.Lett_25_1705
Author(s) : Takai K , Chiyo N , Nakajima T , Nariai T , Ishikawa C , Nakatani S , Ikeno A , Yamamoto S , Sone T
Ref : Bioorganic & Medicinal Chemistry Lett , 25 :1705 , 2015
Abstract : We have previously reported a series of cyclopropyl urea derivatives as potent orally available soluble epoxide hydrolase (sEH) inhibitors. Here, we designed and synthesized three substituted cyclopropane derivatives that occupy all available pockets of sEH catalytic domain. Compound 14 with a diphenyl substituted cyclopropyl moiety showed good sEH inhibitory activity. Co-crystal structure of this compound and human sEH hydrolase catalytic domain revealed enzyme pockets occupied by the phenoxypiperidine part and the diphenyl cyclopropyl moiety. Furthermore, investigation of the phenoxypiperidine part of compound 14 resulted in the discovery of compound 19, which showed potent sEH inhibitory activity (sub-nM sEH IC50 values).
ESTHER : Takai_2015_Bioorg.Med.Chem.Lett_25_1705
PubMedSearch : Takai_2015_Bioorg.Med.Chem.Lett_25_1705
PubMedID: 25800114
Gene_locus related to this paper: human-EPHX2

Related information

Gene_locus related to this paper: human-EPHX2

Citations formats

Takai K, Chiyo N, Nakajima T, Nariai T, Ishikawa C, Nakatani S, Ikeno A, Yamamoto S, Sone T (2015)
Three-dimensional rational approach to the discovery of potent substituted cyclopropyl urea soluble epoxide hydrolase inhibitors
Bioorganic & Medicinal Chemistry Lett 25 :1705

Takai K, Chiyo N, Nakajima T, Nariai T, Ishikawa C, Nakatani S, Ikeno A, Yamamoto S, Sone T (2015)
Bioorganic & Medicinal Chemistry Lett 25 :1705