565460-15-3Relevant academic research and scientific papers
Lipid peroxidation inhibition study: A promising case of 1,3-di([1,1′-biphenyl]-3-yl)urea
Casati, Silvana,Ciuffreda, Pierangela,Ottria, Roberta,Yancheva, Denitsa,?melcerovi?, Andrija,Lazarevi?, Jelena,Zvezdanovi?, Jelena
, (2020/06/08)
In the present study eighteen inhibitors of the hydrolytic enzymes of the endocannabinoid system were investigated for antioxidant activity using lipid peroxidation (LP) method. Among the assayed compounds ten belong to carbamates with phenyl [1,1′-biphenyl]-3-ylcarbamate (6), reported for the first time, and eight are retro-amide derivatives of palmitamine. Interestingly, results indicated that most of the tested compounds have good antioxidant properties. In particular, 1,3-di([1,1′-biphenyl]-3-yl)urea (3) shows IC50 = 26 ± 6 μM comparable to ones obtained for standard antioxidants trolox and quercetin (IC50 = 22 ± 6 μM and 23 ± 6 μM, respectively). Compound 3 was investigated further by means of DFT calculations, to clarify a possible mechanism of the antioxidant action. In order to estimate the capability of 3 to act as radical scavenger the structure was optimized at B3LYP/6–311++G** level and the respective bond dissociation enthalpies were calculated. The calculations in non-polar medium predicted as favorable mechanism a donation of a hydrogen atom to the free radical and formation of N-centered radical, while in polar solvents the mechanism of free radical scavenging by SPLET dominates over HAT H-abstraction. The possible radical scavenging mechanisms of another compound with potent antioxidant properties (IC50 = 53 ± 12 μM), the retro-amide derivative of palmitamine (compound 18), was estimated computationally based on the reaction enthalpies of a model compound (structural analogue to 18). The computations indicated that the most favorable mechanisms are hydrogen atom transfer from the hydroxyl group in meta-position of the benzamide fragment in nonpolar medium, and proton transfer from the hydroxyl group in ortho-position of the benzamide fragment in polar medium.
Synthesis of N-(Hetero)aryl Carbamates via CuI/MNAO Catalyzed Cross-Coupling of (Hetero)aryl Halides with Potassium Cyanate in Alcohols
Kumar, S. Vijay,Ma, Dawei
, p. 2706 - 2713 (2018/03/09)
An efficient route to N-(hetero)aryl carbamates was developed through CuI/MNAO [2-((2-methylnaphthalen-1-yl)amino)-2-oxoacetic acid] catalyzed cross-coupling of (hetero)aryl chlorides with potassium cyanate in alcohols at 120-130 °C. This method utilizes
The design, synthesis and biological evaluation of novel URB602 analogues as potential monoacylglycerol lipase inhibitors
Szabo, Monika,Agostino, Mark,Malone, Daniel T.,Yuriev, Elizabeth,Capuano, Ben
experimental part, p. 6782 - 6787 (2011/12/22)
We have synthesised an extensive series of URB602 analogues as inhibitors of monoacylglycerol lipase (MAGL), which is the major enzyme responsible for metabolising the endocannabinoid 2-arachidonylglycerol. The recently identified crystal structure of MAG
Design, synthesis, and structure - Activity relationships of alkylcarbamic acid aryl esters, a new class of fatty acid amide hydrolase inhibitors
Tarzia, Giorgio,Duranti, Andrea,Tontini, Andrea,Piersanti, Giovanni,Mor, Marco,Rivara, Silvia,Plazzi, Pier Vincenzo,Park, Chris,Kathuria, Satish,Piomelli, Daniele
, p. 2352 - 2360 (2007/10/03)
Fatty acid amide hydrolase (FAAH), an intracellular serine hydrolase enzyme, participates in the deactivation of fatty acid ethanolamides such as the endogenous cannabinoid anandamide, the intestinal satiety factor oleoylethanolamide, and the peripheral analgesic and anti-inflammatory factor palmitoylethanolamide. In the present study, we report on the design, synthesis, and structure-activity relationships (SAR) of a novel class of potent, selective, and systemically active inhibitors of FAAH activity, which we have recently shown to exert potent anxiolytic-like effects in rats. These compounds are characterized by a carbamic template substituted with alkyl or aryl groups at their O- and N-termini. Most compounds inhibit FAAH, but not several other serine hydrolases, with potencies that depend on the size and shape of the substituents. Initial SAR investigations suggested that the requirements for optimal potency are a lipophilic N-alkyl substituent (such as n-butyl or cyclohexyl) and a bent O-aryl substituent. Furthermore, the carbamic group is essential for activity. A 3D-QSAR analysis on the alkylcarbamic acid aryl esters showed that the size and shape of the O-aryl moiety are correlated with FAAH inhibitory potency. A CoMSIA model was constructed, indicating that whereas the steric occupation of an area corresponding to the meta position of an O-phenyl ring improves potency, a region of low steric tolerance on the enzyme active site exists corresponding to the para position of the same ring. The bent shape of the O-aryl moieties that best fit the enzyme surface closely resembles the folded conformations observed in the complexes of unsaturated fatty acids with different proteins. URB524 (N-cyclohexylcarbamic acid biphenyl-3-yl ester, 9g) is the most potent compound of the series (IC50 = 63 nM) and was therefore selected for further optimization.
