16114-24-2

Upstream product

• 1122-17-4 dichloromaleic acid anhydride 
• 100-46-9 benzylamine 
• 108-31-6 maleic anhydride 

Downstream Products

• 16114-38-8 2,6-dibenzyl-1H,5H-[1,4]dithiino[2,3-c:5,6-c']dipyrrole-1,3,5,7(2H,6H)-tetrone 
• 91026-01-6 2,3-bis(1H-indol-3-yl)-N-benzylmaleimide 
• 870987-40-9 1-benzyl-3,4-bis-(2-phenyl-1H-indol-3-yl)-pyrrole-2,5-dione 
• 870987-41-0 1-benzyl-3,4-bis-(2-benzyl-1H-indol-3-yl)-pyrrole-2,5-dione 
• 935525-80-7 1-benzyl-3-chloro-4-isobutylpyrrole-2,5-dione 
• 201216-89-9 3-chloro-2-(cyclopentadienyltricarbonylmolybda)-N-benzylmaleinimide 
• 1109273-59-7 2-benzyl-pyrrolo[3,4-b][1,4]benzoxazine-1,3(2H,9H)-dione 
• 1109273-82-6 2-benzyl-7-tert-butyl-pyrrolo[3,4-b][1,4]benzoxazine-1,3(2H,9H)-dione 
• 1109273-69-9 2-benzyl-7-chloro-pyrrolo[3,4-b][1,4]benzoxazine-1,3(2H,9H)-dione 

Relevant academic research and scientific papers

Supramolecular Inhibition of [4 + 2] Diels-Alder Reactions in Charge-Transfer Crystals

Heteromolecular charge-transfer (CT) crystals formed using 1,4-dithiintetracarboxydiimide type compounds and anthracene derivatives are typically capable of undergoing [4 + 2] Diels-Alder (DA) reactions in the solid state. Several examples have highlighted the single-crystal-to-single-crystal (SCSC) reactivity of these types of CT crystals at temperatures around 20-50 °C. In furthering these studies, CT crystals with bis(N-benzylimino)-1,4-dithiin and various anthracenes were grown, and their structures were elucidated through single crystal X-ray diffraction (six structures in total). The benzyl groups help facilitate CT formation and crystallization through C-H···πinteractions between included anthracene molecules (the electron donor) and the bis(N-benzylimino)-1,4-dithiin (DBn; the electron acceptor molecule), but their subsequent orientations within the stacks in the crystal structure inhibit product formation by preventing the molecular motion required for product formation. Assessment of their solid-state structures showed that the majority of reactive sites comply with Schmidt's criteria. However, two modes of reaction were discovered. If the reaction was carried out quickly (less than an hour), the crystals were stable until their solid-state DA reaction temperature (above 130 °C for all six structures) leading to amorphous crystals of the product where the crystal habit was maintained. However, if the reaction was carried out at 50-70 °C for an extended time of 5 days, the crystals appeared the same as the starting crystals for up to 2 days and steadily discolored until the complete reaction in 5 days enabled by defects that become more pronounced with the reaction time. The crystals were maintained during the process but were amorphous. These results show that although the alignment and separation between molecules are important for solid-state reactivity, so too is the nature and size of the groups in close proximity to the sites of reaction. This opens up the possibility of controlling the direction of a reaction or stopping a reaction altogether through the use of appropriate secondary groups not involved in the reaction itself.

Self-Delivery Nanoparticles of Amphiphilic Acyclic Enediynes for Efficient Tumor Cell Suppression

Four acyclic maleimide-based enediyne compounds with different hydrophilicity were synthesized through Sonogashira reaction to reveal a self-delivery antitumor drug platform. As proved by ESR analysis, the enediyne compounds undergo Bergman-like cyclization and generate diradical intermediates at physiological temperature, which are able to induce DNA-cleavage through the abstraction of H atoms from the sugar-phosphate backbones. When the critical aggregation concentration is reached in water, the amphiphilic enediyne compounds self-assemble into nanoparticles and possess the self-delivery ability to be facilely admitted by tumor cells, resulting in greatly improved cytotoxicity (IC50 down to 10 μmol·L–1) and much higher tumor cell apoptosis rate (up to 86.6%) in comparison with either the hydrophilic or the lipophilic enediyne compound. The enhanced endocytosis of the amphiphilic enediyne compounds was further confirmed through confocal laser scanning microscopy analysis. The unveiled relationship between the hydrophilicity of enediyne drugs and their therapeutic efficacy will provide a guideline for the design of new self-delivery drugs employed in medicinal applications.

Application of maleimide compound as chitin synthase inhibitor

The invention discloses an application of a maleimide compound as shown in a formula I. In the formula I, R0 is phenyl, benzyl, phenethyl, phenylpropyl, p-fluorophenyl, p-chlorophenyl, p-bromophenyl,p-methoxyphenyl, p-methylphenyl or p-hydroxyphenyl, R1 is hydrogen, methyl, phenyl or chlorine; and R2 is hydrogen, methyl, phenyl or chlorine. The provided maleimide compound has a good inhibition effect on chitin synthase.

Preparation and antitumor applications of asymmetric propargyl amide maleimide based enediyne antibiotics

Maleimide-based enediynes with propargyl amide at one arm and other kinds of alkyne at the other arm were synthesized via Sonogashira reaction. The logP values of these enediyne antibiotics were adjusted by changing the alkyl chain length and installing a hydroxyl group. As confirmed by electron paramagnetic resonance analysis, the enediynes generated reactive free radicals at physiological temperature, which endows them the ability to cause DNA cleavage and lead to tumor cell death. While most of the enediynes act in small molecular form, one of them showed amphiphilic property and formed vesicles in deionized water for potential self-delivery applications. The reactive oxygen species level in tumor cells was enhanced in the presence of these enediynes, leading to cell death through apoptosis pathway. The half inhibition concentrations (IC50) of the enediynes towards HeLa cells were on the micromolar level, comparable to many commercial anticancer agents.

Coordination-Accelerated Radical Formation from Acyclic Enediynes for Tumor Cell Suppression

A maleimide-based acyclic enediyne with salicylaldiminato substituents at the alkyne termini was synthesized, which was further chelated with three kinds of metal-ions, CuII, ZnII, and MgII, and form metalloenediynes. The cycloaromatization of this thermally inactive enediyne ligand was greatly accelerated through the coordination with metal ions. Specifically, the CuII-metalloenediyne showed an extremely low onset temperature of 55 °C and underwent spontaneous cycloaromatization at ambient temperature to produce free radicals, followed by generation of reactive oxygen species in the physiological environment. The metalloenediyne exhibited excellent DNA cleavage ability and high cytotoxicity towards HeLa cells, with half-maximal inhibitory concentration values comparable to many commercial antitumor agents. The combination of the electron-withdrawing effect of the maleimide moiety at the ene position and metal coordination at the yne termini provides a new inspiration for designing and synthesizing highly efficient enediyne antitumor agents.

An acyclic enediyne anticancer compound attributed to a Bergman cyclization at physiological temperature

Enediyne cytotoxic drugs have attracted much attention because of their unique structure and potent anticancer activity. However, acyclic enediynes are long considered as inactive at physiological temperature due to their long C1-C6 distance. By adjusting the steric bulkiness of the functional groups at the alkynyl termini and the electron-withdrawing effect at the ene moiety, herein, a simple acyclic enediyne was designed and synthesized to achieve the onset of thermal Bergman cyclization at physiological temperature in polar solvents. The spontaneous generation of diradical intermediates was confirmed through EPR analysis and further supported by spin trapping experiment, radical indicator experiment, and high resolution MS analysis. The reactive diradicals generated in aqueous media induced single and double stranded cleavage of DNA, and showed high cytotoxicity to Hela cells. The IC50 value of the enediyne compound is comparable to many clinical used anti-tumor agents.

Nonsymmetrical 3,4-dithienylmaleimides by cross-coupling reactions with indium organometallics: Synthesis and photochemical studies

The synthesis and photochemical study of novel nonsymmetrical 1,2-dithienylethenes (DTEs) with a maleimide bridge have been carried out. The synthetic approach to the DTEs was based on successive selective palladium-catalyzed cross-coupling reactions of 5-susbtituted-2-methyl-3-thiophenyl indium reagents with 3,4-dichloromaleimides. The required organoindium reagents were prepared from 2-methyl-3,5-dibromothiophene by a selective (C-5) coupling reaction with triorganoindium compounds (R3In) and subsequent metal-halogen exchange. The coupling reactions usually gave good yields and have a high atom economy with substoichiometric amounts of R3In. The results of photochemical studies show that these novel dithienylmaleimides undergo a photocyclization reaction upon irradiation in the UV region and a photocycloreversion after excitation in the visible region, thus they can be used as photochemical switches. ON-OFF operations can be repeated in successive cycles without appreciable loss of effectiveness in the process.

Fluorescent triphenyl substituted maleimide derivatives: Synthesis, spectroscopy and quantum chemical calculations

In this paper we describe a semi-empirical quantum method for predicting the wavelength of maximum fluorescence excitation and emission for several known and new maleimide derivatives. All new maleimides, containing a N-Benzyl attachment, were successfully synthesised via a tandem Suzuki reaction with aryl boronic acids containing either an electron donating, electron withdrawing functional groups. Absorption and emission spectra calculated using the semi-empirical AM1 method with excited state ZINDO calculations proved more reliable than either Hartree-Fock Configuration interaction or time dependent density functional methods. Calculated absorption and emission wavelengths were compared with 26 experimental spectra from known or newly synthesised maleimides and found to have provide reasonable predictions, with an average deviation of less the 6% for absorption maxima and less than 4% for emission peaks. The described method provides a strong benchmark for the accuracy that can be expected from theoretical predictions of fluorescence spectra. Springer Science+Business Media, LLC 2010.

Synthesis of novel 1,4-benzoxazine-2,3-dicarboximides from maleic anhydride and substituted aromatic amines

A series of novel 1,4-benzoxazine-2,3-dicarboximides starting from maleic anhydride and substituted aromatic amines were synthesized. Copyright Taylor & Francis Group, LLC.

Synthesis of 3,4-disubstituted maleimides by selective cross-coupling reactions using indium organometallics

Unsymmetrical 3,4-disubstituted maleimides have been synthesized by palladium-catalyzed cross-coupling reactions of indium organometallics with 3,4-dihalomaleimides. The synthesis was performed by stepwise or sequential one-pot palladium-catalyzed cross-c