Highly efficient, catalyst-free, one-pot, pseudo-seven-component synthesis of novel poly-substituted pyrazolyl-1,2-diazepine derivatives

Mojikhalifeh, Sanaz; Hasaninejad, Alireza

doi:10.1039/c8qo00210j

Cited by 9 publications

(3 citation statements)

References 45 publications

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“…Nitro ketene dithioacetals are known as dicarbon synthons in organic synthesis due to their push-pull electronic nature. Reactions of nitro ketane dithioacetals with a variety of nucleophilic groups have so far been applied to construct various heterocycles 23,24 with diverse biological activities, including antitumor 25,26 , antianxiety 27 , antileishmanial 28 and antibacterial 29 .…”

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confidence: 99%

Design, synthesis, in silico and biological evaluations of novel polysubstituted pyrroles as selective acetylcholinesterase inhibitors against Alzheimer’s disease

Pourtaher

Hasaninejad

Iraji

2022

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The objective of this study was to design new polysubstituted pyrrole derivatives as selective acetylcholinesterase (AChE) inhibitors to target Alzheimer's disease. In this context, a highly efficient, one-pot, sequential, multi-component synthesis of a diverse range of polysubstituted pyrroles was developed through a sequential domino strategy by the condensation of amines with 1,1-bis(methylthio)-2-nitroethene (BMTNE), Knovenagle reaction of arylglyoxals with malono derivatives and subsequent Michael addition and intramolecular cyclization reaction in EtOH at reflux. Thirty-nine synthesized compounds were evaluated as AChE and butyrylcholinesterase (BChE) inhibitors. Among the synthesized compounds, compound 4ad (IC50 = 2.95 ± 1.31 µM) was the most potent and selective AChE inhibitor with no significant inhibition against butyrylcholinesterase BChE. A kinetic study of 4ad revealed that this compound inhibited AChE in an uncompetitive mode. Based on a molecular modeling study, compound 4ad due to its small size properly fitted into the active site of AChE compared to BChE and stabilized by H-bond and hydrophobic interactions with the critical residues of the AChE binding pocket. Consequently, it was proposed that the 4ad derivative can be an ideal lead candidate against AD with a simple and practical operation of synthetic procedures.

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confidence: 99%

Design, synthesis, in silico and biological evaluations of novel polysubstituted pyrroles as selective acetylcholinesterase inhibitors against Alzheimer’s disease

Pourtaher

Hasaninejad

Iraji

2022

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“…In 2018, Hasaninejad and Mojikjalifen 89 reported the synthesis of novel poly substituted pyrazolyl-1,2-diazepine scaffolds via a one-pot pseudo-7CR from condensation of 1,1-bis(methylthio)-2-nitroethylene (BMTNE) ( 563 ), two equivalents of hydrazine ( 564 ), two equivalents of aryl aldehydes 566a–l , and two equivalents of malononitrile ( 567 ) in EtOH as solvent. The synthetic strategy is depicted in the Scheme 58.…”

Section: Pseudo-seven Component Reactions and Morementioning

confidence: 99%

Pseudo-multicomponent reactions

et al. 2023

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“…Green chemistry is about developing processes and technologies that lead to more efficient chemical reactions that produce less waste and less environmental emissions than traditional chemical reactions that decrease the negative effects on human health and the environment 33 , 34 . Mainly, using solvents is a steady source of worry because it gives rise to toxicity, pollution, hazard, and waste treatment issues.…”

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confidence: 99%

The anti-Alzheimer potential of novel spiroindolin-1,2-diazepine derivatives as targeted cholinesterase inhibitors with modified substituents

Pourtaher¹,

Hasaninejad²,

Zare³

et al. 2023

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In this study, a new series of spiro indolin-1,2-diazepine were designed, synthesized, and screened for their cholinesterase inhibitory activities. A novel, green, high-yielding approach was constructed to synthesize spiro indolin-1,2-diazepine derivatives through a cascade reaction of different isatins, malononitrile and 1,1-enediamines (EDAMs) via sequential four-component reactions to produce the target compounds with good to excellent yields. Next the inhibitory potencies of all derivatives were determined spectroscopically at 415 nm using the modified Ellman method. The results of the in vitro screening indicated that 5l with spiroindolin-1,2-diazepine core bearing 5-NO2 at R1 and 4-OH at R2 was the most potent and selective AChE inhibitor with an IC50 value of 3.98 ± 1.07 µM with no significant inhibition against BChE while 5j was the most active analog against both AChE and BChE enzymes. The structure–activity relationships suggested the variation in the inhibitory activities of derivatives was affected by different substitutions on the indolinone ring as well as the phenyl moiety. The enzyme kinetic studies of the most potent compound 5l at five different concentrations and acetylthiocholine substrate (0.1–1 mM) by Ellman's method revealed that it inhibited AChE in a mixed mode with a Ki of 0.044 μM. A molecular docking study was performed via induced fit docking protocol to predict the putative binding interaction. It was shown that the moieties used in the initial structure design play a fundamental role in interacting with the enzyme's binding site. Further, molecular dynamics simulations with the Schrödinger package were performed for 5l in a complex with AChE and revealed that compound 5l formed the stable complex with the enzyme. The MTT toxicity assessments against the neuroblastoma cell line were executed, and no toxicity was seen for 5l under the tested concentrations.

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Highly efficient, catalyst-free, one-pot, pseudo-seven-component synthesis of novel poly-substituted pyrazolyl-1,2-diazepine derivatives

Abstract: A novel, green and high yielding preparation of poly-substituted pyrazolyl-1,2-diazepine derivatives is describedviaa one-pot pseudo-seven-component condensation reaction under catalyst-free conditions in EtOH at room temperature.

Cited by 9 publications

References 45 publications

Design, synthesis, in silico and biological evaluations of novel polysubstituted pyrroles as selective acetylcholinesterase inhibitors against Alzheimer’s disease

Design, synthesis, in silico and biological evaluations of novel polysubstituted pyrroles as selective acetylcholinesterase inhibitors against Alzheimer’s disease

Pseudo-multicomponent reactions

The anti-Alzheimer potential of novel spiroindolin-1,2-diazepine derivatives as targeted cholinesterase inhibitors with modified substituents

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