Optimized Inhibitors of Soluble Epoxide Hydrolase Improve in Vitro Target Residence Time and in Vivo Efficacy was written by Lee, Kin Sing Stephen;Liu, Jun-Yan;Wagner, Karen M.;Pakhomova, Svetlana;Dong, Hua;Morisseau, Christophe;Fu, Samuel H.;Yang, Jun;Wang, Peng;Ulu, Arzu;Mate, Christina A.;Nguyen, Long V.;Hwang, Sung Hee;Edin, Matthew L.;Mara, Alexandria A.;Wulff, Heike;Newcomer, Marcia E.;Zeldin, Darryl C.;Hammock, Bruce D.. And the article was included in Journal of Medicinal Chemistry in 2014.Electric Literature of C16H20F3N3O3 The following contents are mentioned in the article:
Diabetes is affecting the life of millions of people. A large proportion of diabetic patients suffer from severe complications such as neuropathic pain, and current treatments for these complications have deleterious side effects. Thus, alternate therapeutic strategies are needed. Recently, the elevation of epoxy-fatty acids through inhibition of soluble epoxide hydrolase (sEH) was shown to reduce diabetic neuropathic pain in rodents. In this report, the authors describe a series of newly synthesized sEH inhibitors I [R1 = 4-CF3C6H4, 4-CF3OC6H4; (CF3)2CFC6H4, etc.; R2 = MeCO, MeCH2CO, MeCH2CH2CO, etc.] with at least 5-fold higher potency and doubled residence time inside both the human and rodent sEH enzyme than previously reported inhibitors. These inhibitors also have better phys. properties and optimized pharmacokinetic profiles. The optimized inhibitor selected from this new series displayed improved efficacy of almost 10-fold in relieving pain perception in diabetic neuropathic rats as compared to the approved drug, gabapentin, and previously published sEH inhibitors. Therefore, these new sEH inhibitors could be an attractive alternative to treat diabetic neuropathy in humans. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7Electric Literature of C16H20F3N3O3).
1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7) belongs to piperidine derivatives. The piperidine moiety constitutes an important building block for the synthesis of a variety of bioactive natural products, alkaloids and other drugs. Piperidine derivatives bearing a masked aldehyde function in the ε-position are easily transformed into quinolizidine compounds through intramolecular reductive amination.Electric Literature of C16H20F3N3O3
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem