Triazole Ureas Act as Diacylglycerol Lipase Inhibitors and Prevent Fasting-Induced Refeeding was written by Deng, Hui;Kooijman, Sander;van den Nieuwendijk, Adrianus M. C. H.;Ogasawara, Daisuke;van der Wel, Tom;van Dalen, Floris;Baggelaar, Marc P.;Janssen, Freek J.;van den Berg, Richard J. B. H. N.;den Dulk, Hans;Cravatt, Benjamin F.;Overkleeft, Herman S.;Rensen, Patrick C. N.;van der Stelt, Mario. And the article was included in Journal of Medicinal Chemistry in 2017.Product Details of 87694-53-9 This article mentions the following:
Triazole ureas constitute a versatile class of irreversible inhibitors that target serine hydrolases in both cells and animal models. We have previously reported that triazole ureas can act as selective and CNS-active inhibitors for diacylglycerol lipases (DAGLs), enzymes responsible for the biosynthesis of 2-arachidonoyl glycerol (2-AG) that activates cannabinoid CB1 receptor. Here, we report the enantio- and diastereoselective synthesis and structure-activity relationship studies. We found that 2,4-substituted triazole ureas with a biphenylmethanol group provided the most optimal scaffold. Introduction of a chiral ether substituent on the 5-position of the piperidine ring provided ultrapotent inhibitor I (DH376) with picomolar activity. Compound I temporarily reduces fasting-induced refeeding of mice, thereby emulating the effect of cannabinoid CB1-receptor inverse agonists. This was mirrored by II (DO34) but also by the neg. control compound III (DO53) (which does not inhibit DAGL), which indicates the triazole ureas may affect the energy balance in mice through multiple mol. targets. In the experiment, the researchers used many compounds, for example, (S)-tert-Butyl (1-(methoxy(methyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate (cas: 87694-53-9Product Details of 87694-53-9).
(S)-tert-Butyl (1-(methoxy(methyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate (cas: 87694-53-9) belongs to esters. Volatile esters with characteristic odours are used in synthetic flavours, perfumes, and cosmetics. Certain volatile esters are used as solvents for lacquers, paints, and varnishes. Many esters have the potential for conformational isomerism, but they tend to adopt an s-cis (or Z) conformation rather than the s-trans (or E) alternative, due to a combination of hyperconjugation and dipole minimization effects. The preference for the Z conformation is influenced by the nature of the substituents and solvent, if present. Lactones with small rings are restricted to the s-trans (i.e. E) conformation due to their cyclic structure.Product Details of 87694-53-9
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