53616-16-3Relevant articles and documents
Curcumin-inspired cytotoxic 3,5-bis(arylmethylene)-1-(N-(ortho-substituted aryl)maleamoyl)-4-piperidones: A novel group of topoisomerase II alpha inhibitors
Jha, Amitabh,Duffield, Katherine M.,Ness, Matthew R.,Ravoori, Sujatha,Andrews, Gabrielle,Bhullar, Khushwant S.,Rupasinghe, H.P. Vasantha,Balzarini, Jan
, p. 6404 - 6417 (2015/10/05)
Three series of novel 3,5-bis(arylmethylene)-1-(N-(ortho-substituted aryl)maleamoyl)-4-piperidones, designed as simplified analogs of curcumin with maleic diamide tether, were synthesized and bioevaluated. These compounds displayed potent cytotoxicity tow
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.
Inter-Ring Torsions in N-Phenylmaleimide and Its o-Halo Derivatives: An Experimental and Computational Study
Miller, Christopher W.,Hoyle, Charles E.,Valente, Edward J.,Magers, David H.,Joensson, E. Sonny
, p. 6406 - 6412 (2007/10/03)
Structures of N-phenylmaleimide and its o-halophenyl derivatives have been determined in the solid state and show the angle between the phenyl and pyrolinyl ring planes to vary from 49.5° to 83.9° with increasing values for compounds with the larger ortho halophenyl substituents (H F ≤ Cl ≤ Br I). Experimental torsions and trends in the series are supported by semiempirical AM1 and ab initio SCF, DFT, and MP2 calculations. Calculations (AM1) on N-phenylmaleimide modeling the torsional deformation between the rings show that the barrier to planarity has a lower energy than that through a perpendicular conformation. In its o-halo derivatives, molecular planarity is not possible, and torsional deformation proceeds through the perpendicular conformation with diminishing, possibly vanishing, barriers with increasing halogen size. For chloro, bromo, and iodo derivatives, twisted ground-state molecular conformations reside in broad minima essentially centered around the perpendicular conformations. The unusually strong, longer wavelength electronic bands observed in the solution spectra of the series were modeled by Zindo/S CIS computations at the optimum AM1 molecular geometries. The observed lower energy (285-305 nm) band for the parent through the o-bromo derivative appears to arise from a {n(O,N); π (phenyl)} → π*(maleimide) transition. The next higher energy (250-285 nm) band appears to be essentially a phenyl π Ρ π* transition. In the o-iodo derivative, a phenyl π → * (C-I) transition appears to contribute to the longer wavelength band. Trends in the observed electronic spectra in acetonitrile within the series of compounds accord roughly with the results of the computations.
Synthesis of Oxindole Derivatives from N-Alkenyl-o-Chloroanilides with Zero-Valent Nickel Complex
Canoira, L.,Rodriguez, J. G.
, p. 1511 - 1518 (2007/10/02)
Oxindole derivatives have been obtained from N-alkenyl-o-chloroanilides by reaction with tetrakis(triphenylphoaphine)nickel(0) in toluene as solvent in good yields.A detailed analysis of all the products of the reaction allows to confirm the postulated mechanism of the cyclization reaction.The o-chloroanilides of the 3-cyclohexenylacetic acid fails in the cyclization reaction, since the torsional hindrance seems to avoid that the endocyclic double bond may be orthogonally to the ortho-?-nickel complex intermediate on the aromatic ring.
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
