Engaging Isatins in Multicomponent Reactions (MCRs) – Easy Access to Structural Diversity

Brandão, Pedro; Marques, Carolina S.; Carreiro, Elisabete P.; Piñeiro, Marta; Burke, Anthony J.

doi:10.1002/tcr.202000167

Cited by 41 publications

(24 citation statements)

References 298 publications

(325 reference statements)

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“…Intrigued by the lack of reported examples of the isatin‐based Ugi reaction, despite this heterocyclic compound being widely used in MCRs, [19c] we decided to investigate the reactivity at the isatin C3 position. Indeed, while in the classic Ugi reaction the carbonyl compound used is an aldehyde, in our approach we explored the reactivity of C3 carbonyl group of the isatin scaffold, vicinal to the carbonyl group of the cyclic amide.…”

Section: Resultsmentioning

confidence: 99%

Ugi Adducts of Isatin as Promising Antiproliferative Agents with Druglike Properties

et al. 2021

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Multicomponent reactions (MCRs) are a valuable tool for the sustainable synthesis of new molecules in a fast, effective and eco-friendly manner, leading to the generation of structurally diverse libraries. Their application in synthetic organic chemistry and medicinal chemistry, in combination with privileged scaffolds, is gaining momentum in recent years. The Ugi reaction is one of the most widely used MCRs in medicinal chemistry, and it is even used for the synthesis of several active pharmaceutical ingredients. Isatin, known for its biological activities and synthetic versatility, has been vastly used in several MCRs, however it was rarely used in combination with the Ugi reaction. Herein we report the first library of isatin-based Ugi 4 component reaction (U4CR) derivatives. Reaction optimization and scope were thoroughly explored, as well as mechanistic insights were obtained using DFT calculations. The resulting library was evaluated in what concerns its druglike properties, pharmacokinetic profile assessment in silico and antiproliferative activity in vitro, with several compounds bearing interesting druglike properties. Biological screening against six tumor cell lines, showed that the majority of the compounds display antiproliferative activity in the low and sub-micromolar range, with the achievement of nanomolar activity (0.1 nM, 6.5 nM and 5.4 nM against HBL-100, HeLa and WiDr, respectively) for the more active compound.

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Section: Resultsmentioning

confidence: 99%

Ugi Adducts of Isatin as Promising Antiproliferative Agents with Druglike Properties

et al. 2021

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“…On the other hand, multicomponent reactions (MCRs) have been considered as a superior synthetic strategy and an important subset of domino reactions in recent years. MCRs have received considerable attention from both academia and industry because of their various benefits over traditional multistep protocols in the synthesis of novel or complex heterocyclic scaffolds, especially in medicinal chemistry and pharmaceutical industry 41 – 43 . In addition, MCRs are valuable in organic synthesis because of their green chemical aspects such as high atom economy and low waste generation 44 – 46 .…”

Section: Introductionmentioning

confidence: 99%

Chitosan-EDTA-Cellulose network as a green, recyclable and multifunctional biopolymeric organocatalyst for the one-pot synthesis of 2-amino-4H-pyran derivatives

Rostami

Dekamin

Valiey

et al. 2022

Sci Rep

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In this research, cellulose grafted to chitosan by EDTA (Cs-EDTA-Cell) bio-based material is reported and characterized by a series of various methods and techniques such as FTIR, DRS-UV–Vis, TGA, FESEM, XRD and EDX analysis. In fact, the Cs-EDTA-Cell network is more thermally stable than pristine cellulose or chitosan. There is a plenty of both acidic and basic sites on the surface of this bio-based and biodegradable network, as a multifunctional organocatalyst, to proceed three-component synthesis of 2-amino-4H-pyran derivatives at room temperature in EtOH. The Cs-EDTA-Cell nanocatalyst can be easily recovered from the reaction mixture by using filtration and reused for at least five times without significant decrease in its catalytic activity. In general, the Cs-EDTA-Cell network, as a heterogeneous catalyst, demonstrated excellent catalytic activity in an environmentally-benign solvent to afford desired products in short reaction times and required simple experimental and work-up procedure compared to many protocols using similar catalytic systems.

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“…As a representative of the class of privileged structures, isatin and its derivatives are widely used in medicinal chemistry [1,2]. The progressing number of works on synthetic procedures [3] and the studies of this heterocycle push researchers in this area to publish generalized data on one or another type of biological activity [4][5][6][7]. It is due to the manifestation of isatin and its derivatives of a wide spectrum of activity, such as anti-cancer [8][9][10], anti-tubercular [11,12], antibacterial [13], anti-COVID [14,15], fungicidal [16,17], etc (Fig.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and diverse biological activity profile of triethylammonium isatin-3-hydrazones

Богданов¹,

Tsivileva²,

Voloshina³

et al. 2022

ADMET DMPK

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A series of biorelevant triethylammonium isatin hydrazones containing various substituents in the aromatic fragment have been synthesized. Their structure and composition were confirmed by NMR- and IR-spectroscopies, mass-spectrometry and elemental analysis. It was found that some representatives show activity against Staphylococcus aureus and Bacillus cereus higher or at the level of norfloxacin, including methicillin-resistant Staphylococcus aureus strains. The study also showed low hemo- and cytotoxicity (Chang Liver) and high antiaggregatory and anticoagulant activity of these compounds. The high potential of new ammonium isatin-3-acylhydrazones in the search for antimicrobial activity against phytopathogens of bacterial and fungal nature has been shown for the first time.

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Engaging Isatins in Multicomponent Reactions (MCRs) – Easy Access to Structural Diversity

Cited by 41 publications

References 298 publications

Ugi Adducts of Isatin as Promising Antiproliferative Agents with Druglike Properties

Ugi Adducts of Isatin as Promising Antiproliferative Agents with Druglike Properties

Chitosan-EDTA-Cellulose network as a green, recyclable and multifunctional biopolymeric organocatalyst for the one-pot synthesis of 2-amino-4H-pyran derivatives

Synthesis and diverse biological activity profile of triethylammonium isatin-3-hydrazones

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