Synthesis of novel aryl-substituted 2-aminopyridine derivatives by the cascade reaction of 1,1-enediamines with vinamidinium salts to develop novel anti-Alzheimer agents.

Alzheimer's disease (AD), a severe neurodegenerative disorder, imposes socioeconomic burdens and necessitates innovative therapeutic strategies. Current therapeutic interventions are limited and underscore the need for novel inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), enzymes implicated in the pathogenesis of AD. In this study, we report a novel synthetic strategy for the generation of 2-aminopyridine derivatives via a two-component reaction converging aryl vinamidinium salts with 1,1-enediamines (EDAMs) in a dimethyl sulfoxide (DMSO) solvent system, catalyzed by triethylamine (EtN).

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

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.

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

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.

One-pot multi-component synthesis of novel chromeno[4,3-b]pyrrol-3-yl derivatives as alpha-glucosidase inhibitors.

A green and efficient one-pot multi-component protocol was developed for the synthesis of some novel dihydrochromeno[4,3-b]pyrrol-3-yl derivatives through the reaction of arylglyoxals, malono derivatives, and different 4-amino coumarins in ethanol at reflux condition. In this method, all products were obtained in good to excellent yield. Next, all synthesized derivatives were evaluated for their α-glucosidase inhibitory activity.

Λ-[Co((,)-dpen)] 2IB(CF): A Second Generation Air- and Water-Stable Chiral Solvating Agent for Chirality Sensing (dpen = NHCHPhCHPhNH).

When CDCl solutions of chiral racemic molecules containing moderately Lewis basic functional groups are treated with the chiral solvating agent (CSA) Λ-[Co((,)-dpen)] 2IB(CF) (Λ-(,)- 2IB(CF)), baseline-resolved NMR signals are observed for the enantiomers (29 diverse analytes). Only 0.62-100 mol % loadings are required (avg 14.

One-pot, sequential four-component synthesis of novel heterocyclic [3.3.3] propellane derivatives at room temperature.

An efficient, one-pot, two-step, four-component reaction for the synthesis of propellane derivatives is described by the condensation reaction between acenaphthenequinone, malono derivatives, primary amines and β-ketoester or β-diketone derivatives in the presence of triethylamine in ethanol at room temperature. Using this procedure, all the products were obtained in good to excellent yields.

Eco-friendly polyethylene glycol (PEG-400): a green reaction medium for one-pot, four-component synthesis of novel asymmetrical bis-spirooxindole derivatives at room temperature.

PEG-400 has been used as a green and biodegradable polymeric solvent for the one-pot, two-step, multi-component synthesis of novel asymmetrical bis-spirooxindole derivatives by the reaction of -alkyl isatin, isatin derivatives, alkylmalonates and C-H activated carbonyl compounds in the presence of KCO at room temperature. Using this procedure, all the products were obtained in good to excellent yields.

Green synthesis of novel spiro-indenoquinoxaline derivatives and their cholinesterases inhibition activity.

A convenient synthesis of substituted spiroindenoquinoxalines at mild and green conditions was developed. Multicomponent reaction of substituted phenylene diamines, ninhydrin, malononitrile and N,N'-substituted-2-nitroethene-1,1-diamines produced the target compounds. Twelve new spiroindenoquinoxalines were obtained, and their ability in inhibition of acetyl and butyrylcholinesterases were investigated both in vitro and in silico.

Application of PEG-400 as a green biodegradable polymeric medium for the catalyst-free synthesis of spiro-dihydropyridines and their use as acetyl and butyrylcholinesterase inhibitors.

A simple, efficient and green approach for the synthesis of spiro-dihydropyridines derivatives by one-pot multi-component reaction of isatin or acenaphthoquinone derivatives (1 equiv) with malononitrile (1 equiv) and N,N'-substituted-2-nitroethene-1,1-diamines (1 equiv) in PEG-400 under catalyst-free conditions is described. This method provides several advantages such as environmental friendliness, short reaction time, and simple workup procedure for the synthesis of biologically important compounds. The ability of synthesized compounds in inhibition of acetyl and butyrylcholinesterase were investigated both in vitro and in silico.

One-pot, sequential four-component synthesis of benzo[c]pyrano[3,2-a]phenazine, bis-benzo[c]pyrano[3,2-a]phenazine and oxospiro benzo[c]pyrano[3,2-a]phenazine derivatives using 1,4-diazabicyclo[2.2.2]octane (DABCO) as an efficient and reusable solid base catalyst.

1,4-Diazabicyclo[2.2.2]octane (DABCO) has been used as an efficient and reusable solid base catalyst for the one-pot, two-step, four-component synthesis of pyrano[3,2-a]phenazine derivatives by the condensation reaction of 2-hydroxy-1,4-naphthoquinone, 1,2-diamines, carbonyl compounds and alkylmalonates under conventional heating as well as microwave irradiation.

Catalyst-free, one-pot, three-component synthesis of 5-amino-1,3-aryl-₁Η-pyrazole-4-carbonitriles in green media.

An efficient, one-pot, three-component synthesis of various biologically important heterocyclic compounds is described via a tandem Knoevengel-cyclo condensation reaction of aromatic aldehydes, malono derivatives, and phenyl hydrazine derivatives in water and ethanol at room temperature.

Ultrasound-promoted catalyst-free one-pot four component synthesis of 2H-indazolo[2,1-b]phthalazine-triones in neutral ionic liquid 1-butyl-3-methylimidazolium bromide.

A catalyst-free one-pot four component methodology for the synthesis of 2H-indazolo[2,1-b]phthalazine-triones under ultrasonic irradiation at room temperature using 1-butyl-3-methylimidazolium bromide, [Bmim]Br, as a neutral reaction medium is described. A broad range of structurally diverse aldehydes (aromatic aldehydes bearing electron withdrawing and/or electron releasing groups as well as heteroaromatic aldehydes) were applied successfully, and corresponding products were obtained in good to excellent yields without any byproduct.

Catalyst-free one-pot four component synthesis of polysubstituted imidazoles in neutral ionic liquid 1-butyl-3-methylimidazolium bromide.

A catalyst-free one-pot four component methodology for the synthesis of 1,2,4,5-substituted imidazoles under conventional heating and microwave irradiation using 1-butyl-3-methylimidazolium bromide, [Bmim]Br, as a neutral reaction media is described. A broad range of structurally diverse aldehydes (aromatic aldehydes bearing electron withdrawing and/or electron releasing groups as well as heteroaromatic aldehydes) and primary amines (aromatic and aliphatic) were applied successfully, and corresponding products were obtained in good to excellent yields without any byproduct.