Preclinical Characterization of the FAAH Inhibitor JNJ-42165279

详细信息    查看全文

• 作者：John M. Keith ; William M. Jones ; Mark Tichenor ; Jing Liu ; Mark Seierstad ; James A. Palmer ; Michael Webb ; Mark Karbarz ; Brian P. Scott ; Sandy J. Wilson ; Lin Luo ; Michelle L. Wennerholm ; Leon Chang ; Michele Rizzolio ; Raymond Rynberg ; Sandra R. Chaplan ; J. Guy Breitenbucher
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2015
• 出版时间：December 10, 2015
• 年：2015
• 卷：6
• 期：12
• 页码：1204-1208
• 全文大小：350K
• ISSN：1948-5875

文摘

The pre-clinical characterization of the aryl piperazinyl urea inhibitor of fatty acid amide hydrolase (FAAH) JNJ-42165279 is described. JNJ-42165279 covalently inactivates the FAAH enzyme, but is highly selective with regard to other enzymes, ion channels, transporters, and receptors. JNJ-42165279 exhibited excellent ADME and pharmacodynamic properties as evidenced by its ability to block FAAH in the brain and periphery of rats and thereby cause an elevation of the concentrations of anandamide (AEA), oleoyl ethanolamide (OEA), and palmitoyl ethanolamide (PEA). The compound was also efficacious in the spinal nerve ligation (SNL) model of neuropathic pain. The combination of good physical, ADME, and PD properties of JNJ-42165279 supported it entering the clinical portfolio.