title: Design and synthesis of dual modulators of soluble epoxide hydrolase and peroxisome proliferator-activated receptors.
abstract: Metabolic syndrome is a complex condition which often requires the use of multiple medications as a treatment. The resulting problems of polypharmacy are increase in side effects, drug-drug interactions, and its high economic cost. Development of multitarget compounds is a promising strategy to avoid the complications arising from administration of multiple drugs. Modulators of peroxisome proliferator-activated receptors (PPARs) are established agents in the treatment of dyslipidaemia, hyperglycaemia, and insulin resistance. Inhibitors of soluble epoxide hydrolase (sEH) are under evaluation for their use in cardiovascular diseases. In the present study, a series of dual sEH/PPAR modulators containing a pyrrole acidic headgroup and a urea pharmacophore were designed, synthesized, and evaluated in vitro using recombinant enzyme and cell-based assays. Compounds with different activity profiles were obtained which could be used in the treatment of metabolic syndrome.
authors.affiliation: Institute of Pharmaceutical Chemistry, ZAFES/LiFF/OSF Goethe-University Frankfurt, Max-von-Laue-Strasse 9, D-60438 Frankfurt am Main, Germany.
authors.forename: Estel
authors.initials: E
authors.lastname: la Buscató
authors.forename: René
authors.initials: R
authors.lastname: Blöcher
authors.forename: Christina
authors.initials: C
authors.lastname: Lamers
authors.forename: Franca-Maria
authors.initials: FM
authors.lastname: Klingler
authors.forename: Steffen
authors.initials: S
authors.lastname: Hahn
authors.forename: Dieter
authors.initials: D
authors.lastname: Steinhilber
authors.forename: Manfred
authors.initials: M
authors.lastname: Schubert-Zsilavecz
authors.forename: Ewgenij
authors.initials: E
authors.lastname: Proschak
mesh_terms: D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D004851:Epoxide Hydrolases / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D047492:Peroxisome Proliferator-Activated Receptors / Q000737:chemistry*; D012995:Solubility
chemical_list: D047492:Peroxisome Proliferator-Activated Receptors; D004851:Epoxide Hydrolases