ArticleBioorganic & medicinal chemistry2020
Preparation and evaluation of soluble epoxide hydrolase inhibitors with improved physical properties and potencies for treating diabetic neuropathic pain.
Article in Bioorganic & medicinal chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 31 citations in OpenAlex.
- Randomized, double-blind, phase 1a single-ascending dose and food effect studies assessing safety and pharmacokinetics of EC5026 in healthy volunteers.Clinical and translational science · 2024Trial
- Topliss-Guided Optimization of Acetanilide-Based Soluble Epoxide Hydrolase Inhibitors: Exploring the Pentafluorosulfanyl Group as a Potency-Enhancing Motif.ChemMedChem · 2026Article
- Which halogen to choose? Comparing the effects of chlorine and fluorine as bioisosteric substituents in drug design.Chemical science · 2026Review
- Effects of molecular interactions between the exposome and oxylipin metabolism on healthspan.Frontiers in physiology · 2025Review
- Design and Synthesis of Dual-Targeting Inhibitors of sEH and HDAC6 for the Treatment of Neuropathic Pain and Lipopolysaccharide-Induced Mortality.Journal of medicinal chemistry · 2024Article
- How Robust Is the Ligand Binding Transition State?Journal of the American Chemical Society · 2023Article
- Quantification of soluble epoxide hydrolase inhibitors in experimental and clinical samples using the nanobody-based ELISA.Journal of pharmaceutical analysis · 2023Article
- Structure-Directed Discovery of Potent Soluble Epoxide Hydrolase Inhibitors for the Treatment of Inflammatory Diseases.Journal of medicinal chemistry · 2023Article
- Screening and Identification of Novel Soluble Epoxide Hydrolase Inhibitors from Corn Gluten Peptides.Foods (Basel, Switzerland) · 2022Article
- Inhibitory Activity of Quaternary Isoquinoline Alkaloids on Soluble Epoxide Hydrolase.Current issues in molecular biology · 2022Article
- Structure-guided discovery of potent and oral soluble epoxide hydrolase inhibitors for the treatment of neuropathic pain.Acta pharmaceutica Sinica. B · 2022Article
- 2-(Piperidin-4-yl)acetamides as Potent Inhibitors of Soluble Epoxide Hydrolase with Anti-Inflammatory Activity.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Discovery of memantyl urea derivatives as potent soluble epoxide hydrolase inhibitors against lipopolysaccharide-induced sepsis.European journal of medicinal chemistry · 2021Article
- Movement to the Clinic of Soluble Epoxide Hydrolase Inhibitor EC5026 as an Analgesic for Neuropathic Pain and for Use as a Nonaddictive Opioid Alternative.Journal of medicinal chemistry · 2021Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Soluble epoxide hydrolase (sEH), a novel therapeutic target for neuropathic pain, is a largely cytosolic enzyme that degrades epoxy-fatty acids (EpFAs), an important class of lipid signaling molecules. Many inhibitors of sEH have been reported, and to date, the 1,3-disubstituted urea has the highest affinity reported for the sEH among the central pharmacophores evaluated. An earlier somewhat water soluble sEH inhibitor taken to the clinic for blood pressure control had mediocre potency (both affinity and kinetics) and a short in vivo half-life. We undertook a study to overcome these difficulties, but the sEH inhibitors carrying a 1,3-disubstituted urea often suffer poor physical properties that hinder their formulation. In this report, we described new strategies to improve the physical properties of sEH inhibitors with a 1,3-disubstituted urea while maintaining their potency and drug-target residence time (a complementary in vitro parameter) against sEH. To our surprise, we identified two structural modifications that substantially improve the potency and physical properties of sEH inhibitors carrying a 1,3-disubstituted urea pharmacophore. Such improvements will greatly facilitate the movement of sEH inhibitors to the clinic.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.