Identification of a Bioactive Impurity in a Commercial Sample of 6‐Methyl‐2‐<i>p</i>‐Tolylaminobenzo[<i>d</i>][1,3]Oxazin‐4‐One (URB754)

Abstract

The compound URB754 was recently identified as a potent inhibitor of the endocannabinoid-deactivating enzyme monoacylglycerol lipase (MGL) by screening of a commercial chemical library. Based on HPLC/MS, NMR and EI/MS analyses, the present paper shows that the MGL-inhibitory activity attributed to URB754 is in fact due to a chemical impurity present in the commercial sample, identified as bis(methylthio)mercurane. Although this organomercurial compound is highly potent at inhibiting MGL (IC50 = 11.9 +/- 1.1 nM), its biological use is prohibited by its toxicity and target promiscuity.