Sandra Codony1, Elena Valverde1, Rosana Leiva1, José Brea2, M Isabel Loza2, Christophe Morisseau3, Bruce D Hammock3, Santiago Vázquez4. 1. Laboratori de Química Farmacèutica (Unitat Associada al CSIC), Facultat de Farmàcia i Ciències de l'Alimentació, and Institute of Biomedicine (IBUB), Universitat de Barcelona, Av. Joan XXIII 27-31, Barcelona E-08028, Spain. 2. Innopharma Screening Platform, Biofarma Research Group, Centro de Investigación en Medicina Molecular y Enfermedades Crónicas (CIMUS), Universidad de Santiago de Compostela, Spain. 3. Department of Entomology and Nematology, and UCD Comprehensive Cancer Center, University of California, Davis, CA 95616, USA. 4. Laboratori de Química Farmacèutica (Unitat Associada al CSIC), Facultat de Farmàcia i Ciències de l'Alimentació, and Institute of Biomedicine (IBUB), Universitat de Barcelona, Av. Joan XXIII 27-31, Barcelona E-08028, Spain. Electronic address: svazquez@ub.edu.
Abstract
Soluble epoxide hydrolase (sEH) inhibitors are potential drugs for several diseases. Adamantyl ureas are excellent sEH inhibitors but have limited metabolic stability. Herein, we report the effect of replacing the adamantane group by alternative polycyclic hydrocarbons on sEH inhibition, solubility, permeability and metabolic stability. Compounds bearing smaller or larger polycyclic hydrocarbons than adamantane yielded all good inhibition potency of the human sEH (0.4 ≤ IC50 ≤ 21.7 nM), indicating that sEH is able to accommodate inhibitors of very different size. Human liver microsomal stability of diamantane containing inhibitors is lower than that of their corresponding adamantane counterparts.
Soluble epoxide hydrolase (n class="Gene">sEH) inhibitors are potential drugs for several diseases. Adamantyl ureas are excellent sEH inhibitors but have limited metabolic stability. Herein, we report the effect of replacing the adamantane group by alternative polycyclic hydrocarbons on sEH inhibition, solubility, permeability and metabolic stability. Compounds bearing smaller or larger polycyclic hydrocarbons than adamantane yielded all good inhibition potency of the humansEH (0.4 ≤ IC50 ≤ 21.7 nM), indicating that sEH is able to accommodate inhibitors of very different size. Human liver microsomal stability of diamantane containing inhibitors is lower than that of their corresponding adamantane counterparts.
Authors: Sydney Zarriello; Julian P Tuazon; Sydney Corey; Samantha Schimmel; Mira Rajani; Anna Gorsky; Diego Incontri; Bruce D Hammock; Cesar V Borlongan Journal: Prog Neurobiol Date: 2018-11-14 Impact factor: 11.685
Authors: Vladimir Burmistrov; Christophe Morisseau; Dmitry Karlov; Dmitry Pitushkin; Andrey Vernigora; Elena Rasskazova; Gennady M Butov; Bruce D Hammock Journal: Bioorg Med Chem Lett Date: 2020-07-24 Impact factor: 2.823
Authors: Juan Martín-López; Sandra Codony; Clara Bartra; Christophe Morisseau; María Isabel Loza; Coral Sanfeliu; Bruce D Hammock; José Brea; Santiago Vázquez Journal: Pharmaceuticals (Basel) Date: 2021-12-17
Authors: Sandra Codony; Carla Calvó-Tusell; Elena Valverde; Sílvia Osuna; Christophe Morisseau; M Isabel Loza; José Brea; Concepción Pérez; María Isabel Rodríguez-Franco; Javier Pizarro-Delgado; Rubén Corpas; Christian Griñán-Ferré; Mercè Pallàs; Coral Sanfeliu; Manuel Vázquez-Carrera; Bruce D Hammock; Ferran Feixas; Santiago Vázquez Journal: J Med Chem Date: 2021-05-04 Impact factor: 7.446