In 2014,Nicolussi, Simon; Chicca, Andrea; Rau, Mark; Rihs, Sabine; Soeberdt, Michael; Abels, Christoph; Gertsch, Jurg published 《Correlating FAAH and anandamide cellular uptake inhibition using N-alkylcarbamate inhibitors: From ultrapotent to hyperpotent》.Biochemical Pharmacology (Amsterdam, Netherlands) published the findings.Category: esters-buliding-blocks The information in the text is summarized as follows:
Besides the suggested role of a putative endocannabinoid membrane transporter mediating the cellular uptake of the endocannabinoid anandamide (AEA), this process is intrinsically coupled to AEA degradation by the fatty acid amide hydrolase (FAAH). Differential blockage of each mechanism is possible using specific small-mol. inhibitors. Starting from the natural product-derived 2E,4E-dodecadiene scaffold previously shown to interact with the endocannabinoid system (ECS), a series of diverse N-alkylcarbamates were prepared with the aim of generating novel ECS modulators. While being inactive at cannabinoid receptors and monoacylglycerol lipase, these N-alkylcarbamates showed potent to ultrapotent picomolar FAAH inhibition in U937 cells. Overall, a highly significant correlation (Spearman’s rho = 0.91) was found between the inhibition of FAAH and AEA cellular uptake among 54 compounds Accordingly, in HMC-1 cells lacking FAAH expression the effect on AEA cellular uptake was dramatically reduced. Unexpectedly, 3-(4,5-dihydrothiazol-2-yl)phenyl carbamates and the 3-(1,2,3-thiadiazol-4-yl)phenyl carbamates WOBE490, WOBE491 and WOBE492 showed a potentiation of cellular AEA uptake inhibition in U937 cells, resulting in unprecedented femtomolar (hyperpotent) IC50 values. Potential methodol. issues and the role of cellular accumulation of selected probes were investigated. It is shown that albumin impacts the potency of specific N-alkylcarbamates and, more importantly, that accumulation of FAAH inhibitors can significantly increase their effect on cellular AEA uptake. Taken together, this series of N-alkylcarbamates shows a FAAH-dependent inhibition of cellular AEA uptake, which can be strongly potentiated using specific head group modifications. These findings provide a rational basis for the development of hyperpotent AEA uptake inhibitors mediated by ultrapotent FAAH inhibition. In addition to this study using Methyl 3-hydroxypropanoate, there are many other studies that have used Methyl 3-hydroxypropanoate(cas: 6149-41-3Category: esters-buliding-blocks) was used in this study.
Methyl 3-hydroxypropanoate(cas: 6149-41-3) belongs to esters with low molecular weight are commonly used as fragrances and found in essential oils and pheromones. Their flexibility and low polarity is manifested in their physical properties; they tend to be less rigid (lower melting point) and more volatile (lower boiling point) than the corresponding amides. Category: esters-buliding-blocks
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics