3,4-Disubstituted maleimides: synthesis and biological activity

Panov, Alexey A.; Simonov, Alexander Y.; Лавренов, С. Н.; Lakatosh, S. A.; Тренин, А. С.

doi:10.1007/s10593-018-2240-z

Cited by 34 publications

(13 citation statements)

References 71 publications

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“…In this article, we make for the first time a systematic study of the impact of DES choline chloride/ p -toluenesulfonic acid ChCl/TsOH and DES choline chloride/ p -toluenesulfonic acid–water ChCl/TsOH/H 2 O in the aza-Michael addition of arylamines 2 to maleimide 1 to obtain aminopyrrolidine-2,5-dione derivatives 3 under very mild reaction conditions with high yield. The derivatives are of great importance in biology, materials science, and chemistry; they are used as synthetic blocks to obtain small bioactive molecules, natural products, drugs, and agrochemicals. − This contribution complements our previous work on nucleophilic addition reactions in α,β-unsaturated carbonyl compounds (maleimide and maleic anhydride) − that were made in terms of the local hard and soft acid and base principle and the density functional theory. − Now, our experimental and theoretical studies on the aza-Michael addition have been motived for two overarching goals: (i) development of a new experimental methodology under mild reaction conditions for fast and efficient synthesis of 3 , through the aza-Michael additions of 2 to 1 using ChCl/TsOH and water as solvents without the need of a catalyst, ligand, and/or additive and (ii) understanding the kinetics and thermodynamics of the interactions between ChCl/TsOH and the reagents and the effect of water on the supramolecular network of ChCl/TsOH using spectroscopic techniques and a potential energy surface.…”

Section: Introductionmentioning

confidence: 85%

Deep Eutectic Solvent Choline Chloride/p-toluenesulfonic Acid and Water Favor the Enthalpy-Driven Binding of Arylamines to Maleimide in Aza-Michael Addition

et al. 2020

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Deep eutectic solvents (DESs) have been considered "the organic reaction medium of the century" because they can be used as solvents and active catalysts in chemical reactions. However, experimental and theoretical studies are still needed to provide information on the structures of DESs, the kinetics and thermodynamics properties, the interactions between the DESs and the substrates, the effect of water on the DES supramolecular network and its physicochemical properties, and so forth. This information is very useful to understand the essence of the processes that take place in the catalysis of chemical reactions and, therefore, to help in the design of a DES for a specific reaction and sample. This article shows a systematic study of the impact of DES choline chloride/p-toluenesulfonic acid and DES choline chloride/ p-toluenesulfonic acid−water in the aza-Michael addition of arylamines to maleimide to obtain aminopyrrolidine-2,5-dione derivatives. The derivatives are obtained under very mild reaction conditions with good yield. The global reaction is exothermic, spontaneous, permitted by enthalpy, and prohibited for entropy. The calculated potential energy surface shows a reaction mechanism of six steps controlled by enthalpy (except the last step that is controlled by entropy). The water incorporated in the supramolecular DES complex stabilizes the transition states and favors the enthalpy-driven binding. A set of H/D exchange NMR experiments validates the transition state existing in the fourth stage of the mechanism.

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Section: Introductionmentioning

confidence: 85%

Deep Eutectic Solvent Choline Chloride/p-toluenesulfonic Acid and Water Favor the Enthalpy-Driven Binding of Arylamines to Maleimide in Aza-Michael Addition

et al. 2020

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“…The reaction between maleic anhydride and the primary amine successfully afforded probe 1 . 32 However, such a strategy did not work for the preparation of probes 2–4 , which contain 7-aminocoumarin scaffolds. Alternatively, 7-((2-bromoethyl)amino)-coumarin 2b and the alkylated products (methylated 3a and ethylated 4a ) were first constructed by substitution reactions.…”

Section: Resultsmentioning

confidence: 99%

Rapid GSH detection and versatile peptide/protein labelling to track cell penetration using coumarin-based probes

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et al. 2023

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“…Indole and maleimide moieties are present in the biologically active natural product and FDA-accepted drugs, making them appropriate for G4 targeting. , Bisindolylmaleimide ( BIM ) scaffold, consisting of indole and maleimide moieties, is found in several lead molecules that act as protein kinase C inhibitors . Herein, we have designed and synthesized a new class of trialkylated - BIM ligands (Figure ).…”

Section: Resultsmentioning

confidence: 99%

Bisindolylmaleimide Ligands Stabilize c-MYC G-Quadruplex DNA Structure and Downregulate Gene Expression

et al. 2022

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G-Quadruplex (G4) structures play a pivotal role in diverse biological functions, including essential processes, such as telomere maintenance and gene regulation. G4 structures formed in functional regions of genomes are actively pursued toward therapeutics and are targeted by small-molecule ligands that alter their structure and/or stability. Herein, we report the synthesis of bisindolylmaleimide-based (BIM) ligands, which preferentially stabilize parallel G4 structures of c-MYC and c-KIT oncogenes over the telomeric h-RAS1 G4 and duplex DNAs. The preferential stabilization of parallel G4s with BIM ligands is further validated by the DNA polymerase stop assay, where stop products were only observed for templates containing the c-MYC G4 sequence. Nuclear magnetic resonance (NMR) titration studies indicate that the lead ligand BIM-Pr1 forms a 2:1 complex with c-MYC G4 DNA with a K D of 38 ± 5 μM. The BIM ligand stacks at the 5′ and 3′ quartets, with molecular modeling and dynamics studies supporting the proposed binding mode. The ligand is cytotoxic to HeLa cells and downregulates c-MYC gene expression. Collectively, the results present bisindolylmaleimide scaffolds as novel and powerful G4 targeting agents.

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3,4-Disubstituted maleimides: synthesis and biological activity

Cited by 34 publications

References 71 publications

Deep Eutectic Solvent Choline Chloride/p-toluenesulfonic Acid and Water Favor the Enthalpy-Driven Binding of Arylamines to Maleimide in Aza-Michael Addition

Deep Eutectic Solvent Choline Chloride/p-toluenesulfonic Acid and Water Favor the Enthalpy-Driven Binding of Arylamines to Maleimide in Aza-Michael Addition

Rapid GSH detection and versatile peptide/protein labelling to track cell penetration using coumarin-based probes

Bisindolylmaleimide Ligands Stabilize c-MYC G-Quadruplex DNA Structure and Downregulate Gene Expression

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