One-Step Conversion of Azine <i>N</i>‑Oxides to α‑<i>N</i>‑Aryltriflamidoazines

Various pyridine, quinoline, isoquinoline, and pyrimidine <i>N</i>-oxides were converted to their corresponding α-<i>N</i>-aryltriflamidoheteroarenes in good yield by treatment with <i>N</i>-aryltriflimides, both neat and in solution, at temperatures ranging from rt to 100 °C

Preclinical Characterization of the FAAH Inhibitor JNJ-42165279

The pre-clinical characterization of the aryl piperazinyl urea inhibitor of fatty acid amide hydrolase (FAAH) <b>JNJ-42165279</b> is described. <b>JNJ-42165279</b> covalently inactivates the FAAH enzyme, but is highly selective with regard to other enzymes, ion channels, transporters, and receptors. <b>JNJ-42165279</b> 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 <b>JNJ-42165279</b> supported it entering the clinical portfolio

Aryl Piperazinyl Ureas as Inhibitors of Fatty Acid Amide Hydrolase (FAAH) in Rat, Dog, and Primate

A series of aryl piperazinyl ureas that act as covalent inhibitors of fatty acid amide hydrolase (FAAH) is described. A potent and selective (does not inhibit FAAH-2) member of this class, JNJ-40355003, was found to elevate the plasma levels of three fatty acid amides: anandamide, oleoyl ethanolamide, and palmitoyl ethanolamide, in the rat, dog, and cynomolgous monkey. The elevation of the levels of these lipids in the plasma of monkeys suggests that FAAH-2 may not play a significant role in regulating plasma levels of fatty acid ethanolamides in primates