Movement to the Clinic of Soluble Epoxide Hydrolase Inhibitor EC5026 as an Analgesic for Neuropathic Pain and for Use as a Nonaddictive Opioid Alternative was written by Hammock, Bruce D.;McReynolds, Cindy B.;Wagner, Karen;Buckpitt, Alan;Cortes-Puch, Irene;Croston, Glenn;Lee, Kin Sing Stephen;Yang, Jun;Schmidt, William K.;Hwang, Sung Hee. And the article was included in Journal of Medicinal Chemistry in 2021.Synthetic Route of C16H20F3N3O3 The following contents are mentioned in the article:
This report describes the development of an orally active analgesic that resolves inflammation and neuropathic pain without the addictive potential of opioids. EC5026 (I) acts on the cytochrome P 450 branch of the arachidonate cascade to stabilize epoxides of polyunsaturated fatty acids (EpFA), which are natural mediators that reduce pain, resolve inflammation, and maintain normal blood pressure. EC5026 is a slow-tight binding transition-state mimic that inhibits the soluble epoxide hydrolase (sEH) at picomolar concentrations The sEH rapidly degrades EpFA; thus, inhibiting sEH increases EpFA in vivo and confers beneficial effects. This mechanism addresses disease states by shifting endoplasmic reticulum stress from promoting cellular senescence and inflammation toward cell survival and homeostasis. We describe the synthesis and optimization of EC5026 and its development through human Phase 1a trials with no drug-related adverse events. Addnl., we outline fundamental work leading to discovery of the analgesic and inflammation-resolving CYP450 branch of the arachidonate cascade. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7Synthetic Route of C16H20F3N3O3).
1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7) belongs to piperidine derivatives. Piperidine and its derivatives have become increasingly popular in many synthetic schemes. Fluorinated piperidines are also the subject of continued interest in medicinal chemistry, for example in the synthesis of selective dipeptidyl peptidase II (DPP II) inhibitors. Piperidine derivatives are also used in solid-phase peptide synthesis (SPPS) and many degradation reactions.Synthetic Route of C16H20F3N3O3
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem