86162-56-3Relevant academic research and scientific papers
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 antifungal activity of N-(alkyl/aryl)-2-(3-oxo-1,4- benzothiazin-2-yl)acetamide
Gupta,Wagh
, p. 697 - 702 (2007/10/03)
A series of N-(alkyl/aryl)-2-(3-oxo-1,4-benzothiazin-2-yl)acetamide have been synthesized by condensation of substituted amines with maleic anhydride (MA) followed by cyclization with o-aminothiophenol (o-ATP). All the compounds have been screened for their antifungal activity against Tricophyton rubrum, Epidermophyton floccosum and Malassazia furfur. In the primary screening, some of the compounds exhibited appreciable activity. The structures of the synthesized compounds 7a-z have been established on the basis of elemental analysis and spectral data.
Non-hydroxylic clathrate hosts of [4 + 2]π cycloadducts of phencyclone and N-arylmaleimides: Recognition of aromatic guests
Yoshitake, Yasuyuki,Misaka, Junichi,Setoguchi, Koji,Abe, Masaki,Kawaji, Tomohiro,Eto, Masashi,Harano, Kazunobu
, p. 1611 - 1619 (2007/10/03)
A series of non-hydroxylic crystalline host compounds, [4 + 2]π cycloadducts of phencyclone and N-arylmaleimides having a bicyclo[2.2.1]heptene-7-one system, was synthesized and their inclusion behavior investigated. X-Ray crystal analyses of the inclusion compounds of the N-(1-naphthyl) derivative with butan-2-one, the N-(m-tolyl) derivative with p-xylene, together with the guest-free host and the N-(p-tolyl) derivative with m-xylene indicate that the "space" surrounded by the phenanthrene ring, two phenyl rings and bridge carbonyl of the 1,3-diphenyl-1,3-dihydrocyclopenta[l]phenanthren-2-one moiety plays an important role, not only in the formation of inclusion complexes with the aromatic guests but also in host-host interactions. In every case, the N-aryl succinimide assists complex formation with the guests, in which the weak lattice forces due to C-H ... π and C-H ... O interactions are operative. Methyl-substituted benzenes are effectively recognized by the C-H ... π interactions between the guest molecules and the phenanthrene ring of the hosts.
Ortho Substituent Effects in Amide Hydrolysis of Maleanilic Acid Derivatives. Stabilization of Positive Charge Developed in the Transition State
Suh, Junghun,Kim, Mahn Joo,Kim, Chong Bok
, p. 2453 - 2456 (2007/10/02)
The effects of ortho substituents on the rate of the hydrolysis of maleanilic acid derivatives have been studied.The rate is enhanced up to 55 times by polar substituents, while it is retarded greatly by nonpolar substituents.The acceleration by the polar
