339159-93-2Relevant articles and documents
Synthesis and in vitro evaluation of N-substituted maleimide derivatives as selective monoglyceride lipase inhibitors
Matuszak, Nicolas,Muccioli, Giulio G.,Labar, Geoffray,Lambert, Didier M.
experimental part, p. 7410 - 7420 (2010/04/30)
The endocannabinoid 2-arachidonoylglycerol (2-AG) plays a major role in many physiological processes, and its action is quickly terminated via enzymatic hydrolysis catalyzed by monoglyceride lipase (MGL). Regulating its endogenous level could offer therapeutic opportunities; however, few selective MGL inhibitors have been described so far. Here, we describe the synthesis of N-substituted maleimides and their pharmacological evaluation on the recombinant human fatty acid amide hydrolase (FAAH) and on the purified human MGL. A few N-arylmaleimides were previously described (Saario, S. M.; Salo, O. M.; Nevalainen, T.; Poso, A.; Laitinen, J. T.; Jarvinen, T.; Niemi, R. Characterization of the Sulfhydryl-Sensitive Site in the Enzyme Responsible for Hydrolysis of 2-Arachidonoylglycerol in Rat Cerebellar Membranes. Chem. Biol. 2005, 12, 649-656) as MGL inhibitors, and along these lines, we present a new set of maleimide derivatives that showed low micromolar IC50 and high selectivity toward MGL vs FAAH. Then, structure-activity relationships have been investigated and, for instance, 1-biphenyl-4-ylmethylmaleimide inhibits MGL with an IC50 value of 790 nM. Furthermore, rapid dilution experiments reveal that these compounds act as irreversible inhibitors. In conclusion, N-substituted maleimides constitute a promising class of potent and selective MGL inhibitors.
Synthesis and spectroscopic evidences of N-arylmaleimides and N-aryl-2,3-dimethylmaleimides
Fles, Dragutin,Vukovic, Radivoje,Kuzmic, Ana Erceg,Bogdanic, Grozdana,Pilizota, Vlasta,Karlovic, Damir,Markus, Kresimir,Wolsperger, Kristina,Vikic-Topic, Drazen
, p. 69 - 74 (2007/10/03)
A series of N-arylmaleimides (N-aryl-MI) and N-aryl-2,3-dimethylmaleimides (N-aryl-DiMeMI) were prepared by condensation of primary amines with maleic anhydride (MAn) and 2,3-dimethylmaleic anhydride (DiMeMAn), respectively. Preparation of N-aryl-MI proceeded through the formation of N-arylmaleamic acid, which subsequently cyclized to N-aryl-MI. In the reaction of N-arylamines with DiMeMAn, cyclic condensation products were formed in one step. By means of one- and two-dimensional 1H and 13C NMR spectroscopy it was proven that N-aryl-DiMeMI and not isomaleimides were formed by a one step reaction.
INFLUENCE OF MEDIUM AND SUBSTITUENTS ON ACYLATION OF AROMATIC AMINES AND THEIR POLYMERIC ANALOGS WITH MALEIC ANHYDRIDE
Donya, A. P.,Pakter, M. K.,Sokhina, S. I.
, p. 2093 - 2097 (2007/10/02)
Correlation relationships describing the influence of substituents and solvents on the rate of acylation of aromatic amines and their polymeric analogs with maleic anhydride have been derived.
