Design and Potency of Dual Soluble Epoxide Hydrolase/Fatty Acid Amide Hydrolase Inhibitors was written by Kodani, Sean D.;Wan, Debin;Wagner, Karen M.;Hwang, Sung Hee;Morisseau, Christophe;Hammock, Bruce D.. And the article was included in ACS Omega in 2018.Formula: C11H20N2O2S This article mentions the following:
Fatty acid amide hydrolase (FAAH) is responsible for regulating concentrations of the endocannabinoid arachidonoyl ethanolamide (AEA). Multiple FAAH inhibitors have been developed for clin. trials and have failed to demonstrate efficacy at treating pain, despite promising preclin. data. One approach towards increasing the efficacy of FAAH inhibitors is to concurrently inhibit other targets responsible for regulating pain. Here, the authors designed dual inhibitors targeting the enzymes FAAH and soluble epoxide hydrolase (sEH), which are targets previously shown to synergize at reducing inflammatory and neuropathic pain. Exploration of the sEH/FAAH inhibitor structure activity relationship started with PF-750, a FAAH inhibitor (IC50 = 19 nM) that weakly inhibited sEH (IC50 = 640 nM). Potency was optimized resulting in an inhibitor with improved potency on both targets (11, sEH IC50 = 5 nM, FAAH IC50 = 8 nM). This inhibitor demonstrated good target selectivity, pharmacokinetic properties (AUC = 1200 h*nM, t1/2=4.9 h in mice) and in vivo target engagement. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-carbamothioylpiperidine-1-carboxylate (cas: 214834-18-1Formula: C11H20N2O2S).
tert-Butyl 4-carbamothioylpiperidine-1-carboxylate (cas: 214834-18-1) belongs to pyridine derivatives. In contrast to benzene, Pyridine’s electron density is not evenly distributed over the ring, reflecting the negative inductive effect of the nitrogen atom. Several pyridine derivatives play important roles in biological systems. While its biosynthesis is not fully understood, nicotinic acid (vitamin B3) occurs in some bacteria, fungi, and mammals.Formula: C11H20N2O2S