title: Synthesis and structure-activity relationship of piperidine-derived non-urea soluble epoxide hydrolase inhibitors.
abstract: A series of potent amide non-urea inhibitors of soluble epoxide hydrolase (sEH) is disclosed. The inhibition of soluble epoxide hydrolase leads to elevated levels of epoxyeicosatrienoic acids (EETs), and thus inhibitors of sEH represent one of a novel approach to the development of vasodilatory and anti-inflammatory drugs. Structure-activities studies guided optimization of a lead compound, identified through high-throughput screening, gave rise to sub-nanomolar inhibitors of human sEH with stability in human liver microsomal assay suitable for preclinical development.
authors.affiliation: Department of Medicine, Columbia University, 650 W 168th Street, BB1029, New York, NY 10032, USA.
authors.forename: Stevan
authors.initials: S
authors.lastname: Pecic
authors.forename: Svetlana
authors.initials: S
authors.lastname: Pakhomova
authors.forename: Marcia E
authors.initials: ME
authors.lastname: Newcomer
authors.forename: Christophe
authors.initials: C
authors.lastname: Morisseau
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Hammock
authors.forename: Zhengxiang
authors.initials: Z
authors.lastname: Zhu
authors.forename: Alison
authors.initials: A
authors.lastname: Rinderspacher
authors.forename: Shi-Xian
authors.initials: SX
authors.lastname: Deng
mesh_terms: D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020134:Catalytic Domain; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors*; D006801:Humans; D020128:Inhibitory Concentration 50; D008862:Microsomes, Liver / Q000201:enzymology; D008958:Models, Molecular; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D012995:Solubility; D013329:Structure-Activity Relationship; D014508:Urea / Q000737:chemistry / Q000494:pharmacology; D014665:Vasodilator Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D010880:Piperidines; D011480:Protease Inhibitors; D014665:Vasodilator Agents; C032727:piperidine; D014508:Urea; D004851:Epoxide Hydrolases