158860-99-2Relevant academic research and scientific papers
ORALLY AVAILABLE SEH/PDE4 DUAL INHIBITORS
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Paragraph 0150; 0158; 0159-0161, (2019/05/10)
Provided herein are novel bioavailable dual inhibitors capable of inhibiting both soluble epoxide hydrolase (sEH) and phosphodiesterase 4 (PDE4), and methods of using the same.
Orally Available Soluble Epoxide Hydrolase/Phosphodiesterase 4 Dual Inhibitor Treats Inflammatory Pain
Bl?cher, René,Wagner, Karen M.,Gopireddy, Raghavender R.,Harris, Todd R.,Wu, Hao,Barnych, Bogdan,Hwang, Sung Hee,Xiang, Yang K.,Proschak, Ewgenij,Morisseau, Christophe,Hammock, Bruce D.
, p. 3541 - 3550 (2018/05/01)
Inspired by previously discovered enhanced analgesic efficacy between soluble epoxide hydrolase (sEH) and phosphodiesterase 4 (PDE4) inhibitors, we designed, synthesized and characterized 21 novel sEH/PDE4 dual inhibitors. The best of these displayed good efficacy in in vitro assays. Further pharmacokinetic studies of a subset of four selected compounds led to the identification of a bioavailable dual inhibitor N-(4-methoxy-2-(trifluoromethyl)benzyl)-1-propionylpiperidine-4-carboxamide (MPPA). In a lipopolysaccharide induced inflammatory pain rat model, MPPA rapidly increased in the blood (Tmax = 30 min; Cmax = 460 nM) after oral administration of 3 mg/kg and reduced inflammatory pain with rapid onset of action correlating with blood levels over a time course of 4 h. Additionally, MPPA does not alter self-motivated exploration of rats with inflammatory pain or the withdrawal latency in control rats.
Selective Type IV Phosphodiesterase Inhibitors as Antiasthmatic Agents. The Syntheses and Biological Activities of 3-(Cyclopentyloxy)-4-methoxybenzamides and Analogues
Ashton, Michael J.,Cook, David C.,Fenton, Garry,Karlsson, Jan-Anders,Palfreyman, Malcolm N.,et al.
, p. 1696 - 1703 (2007/10/02)
The syntheses and biological activities of a number of benzamide derivatives, designed from rolipram, which are selective inhibitors of cyclic AMP-specific phosphodiesterase (PDE IV), are described.The effects of changes to the alkoxy groups, amide linkag
