title: Rapid synthesis of an array of trisubstituted urea-based soluble epoxide hydrolase inhibitors facilitated by a novel solid-phase method.
abstract: A 270-membered library of trisubstituted ureas was synthesized and evaluated for inhibition of soluble epoxide hydrolase. Library design and reagent selection was guided by the use of a pharmacophore model and synthesis of the array was enabled with a general solid-phase method. This array approach facilitated multi-dimensional SAR around this series and identified functionality responsible for binding affinity, as well as opportunities for modulating the overall in vitro profiles of this class of soluble epoxide hydrolase inhibitors.
authors.affiliation: Department of Medicinal Chemistry, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877, USA. jennifer.kowalski@boehringer-ingelheim.com
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Kowalski
authors.forename: Alan D
authors.initials: AD
authors.lastname: Swinamer
authors.forename: Ingo
authors.initials: I
authors.lastname: Muegge
authors.forename: Anne B
authors.initials: AB
authors.lastname: Eldrup
authors.forename: Alison
authors.initials: A
authors.lastname: Kukulka
authors.forename: Charles L
authors.initials: CL
authors.lastname: Cywin
authors.forename: Stéphane
authors.initials: S
authors.lastname: De Lombaert
mesh_terms: D000818:Animals; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis*; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors*; D006801:Humans; D011485:Protein Binding; D054852:Small Molecule Libraries / Q000138:chemical synthesis*; D012995:Solubility; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D004791:Enzyme Inhibitors; D054852:Small Molecule Libraries; D014508:Urea; D004851:Epoxide Hydrolases