78564-19-9

Upstream product

• 5447-87-0 2-(1-phenylethylidene)propanedinitrile 
• 97651-32-6 p-tolylmethylenecyanothioacetamide 
• 77609-10-0 2-(3-oxo-1-phenyl-3-(p-tolyl)propyl)malononitrile 
• 4224-96-8 3-phenyl-1-p-tolylprop-2-en-1-one 
• 122-00-9 para-methylacetophenone 
• 100-52-7 benzaldehyde 
• 7357-70-2 Cyanothioacetamide 
• 94360-18-6 2-Bromo-2-(3-oxo-1-phenyl-3-p-tolyl-propyl)-malononitrile 

Downstream Products

• 78564-37-1 3-Amino-4-phenyl-6-p-tolyl-thieno[2,3-b]pyridine-2-carbonitrile 
• 78564-36-0 3-Amino-6-(4-methoxy-phenyl)-4-phenyl-thieno[2,3-b]pyridine-2-carbonitrile 
• 78564-29-1 2-Cyanomethylsulfanyl-4-phenyl-6-p-tolyl-nicotinonitrile 
• 94360-94-8 2-(2-Oxo-2-p-tolyl-ethylsulfanyl)-4-phenyl-6-p-tolyl-nicotinonitrile 
• 169304-03-4 Acetic acid (2R,3R,4S,5R)-4,5-diacetoxy-2-(3-cyano-4-phenyl-2-thioxo-6-p-tolyl-2H-pyridin-1-yl)-tetrahydro-pyran-3-yl ester 
• 78564-40-6 8-amino-2-(4-tolyl)-4-phenylpyrido<2',3':2,3>thieno<4,5-d>pyrimide 
• 174196-09-9 Acetic acid (2R,3R,4S,5S,6R)-4,5-diacetoxy-6-acetoxymethyl-2-(3-cyano-4-phenyl-2-thioxo-6-p-tolyl-2H-pyridin-1-yl)-tetrahydro-pyran-3-yl ester 
• 174196-08-8 Acetic acid (2R,3R,4S,5R,6R)-4,5-diacetoxy-6-acetoxymethyl-2-(3-cyano-4-phenyl-2-thioxo-6-p-tolyl-2H-pyridin-1-yl)-tetrahydro-pyran-3-yl ester 
• 94360-96-0 (3-Amino-4-phenyl-6-p-tolyl-thieno[2,3-b]pyridin-2-yl)-(4-chloro-phenyl)-methanone 
• 94360-95-9 (3-Amino-4-phenyl-6-p-tolyl-thieno[2,3-b]pyridin-2-yl)-(4-fluoro-phenyl)-methanone 
• 94360-82-4 3-Amino-4-phenyl-6-p-tolyl-thieno[2,3-b]pyridine-2-carboxylic acid ethyl ester 
• 94360-97-1 (3-Amino-4-phenyl-6-p-tolyl-thieno[2,3-b]pyridin-2-yl)-phenyl-methanone 
• 94360-81-3 3-Amino-4-phenyl-6-p-tolyl-thieno[2,3-b]pyridine-2-carboxylic acid methyl ester 
• 94360-92-6 2-[2-(4-Fluoro-phenyl)-2-oxo-ethylsulfanyl]-4-phenyl-6-p-tolyl-nicotinonitrile 

Relevant academic research and scientific papers

Novel nicotinonitrile-coumarin hybrids as potential acetylcholinesterase inhibitors: design, synthesis, in vitro and in silico studies

Abstract: Alzheimer’s disease is a degenerative brain condition that is the leading cause of dementia affecting millions of people around the world. Therapeutic development has focused on the problem of the loss of basal forebrain cholinergic function, as it is the only evidence responsible for brain neurodegeneration in patients with Alzheimer’s disease. Several attempts to improve cholinergic neurotransmission have been investigated by minimizing synaptic degradation of acetylcholine using acetylcholinesterase inhibitors. In the current study, we explore the designing of a new series of nicotinonitrile-coumarin hybrids as potential acetylcholinesterase inhibitors. The new hybrids were prepared utilizing pyridine-2(1H)-thiones as starting precursors. The in vitro acetylcholinesterase (AChE) inhibitory activities were examined for the new nicotinonitrile-coumarin hybrid molecules, when compared with donepezil as a standard drug with IC50 of 14?nM. Coumarin derivative, linked to 6-(4-nitrophenyl)-4-phenylnicotinonitrile, showed more effective inhibitory activity than the reference donepezil with IC50 of 13?nM. The free radical-scavenging capabilities against DPPH of the new hybrid derivatives were screened. Additionally, their in vitro cytotoxic activities have been tested against various eukaryotic cells. Furthermore, docking study showed excellent interaction between nicotinonitrile-coumarin hybrids and AChE. Graphic abstract: [Figure not available: see fulltext.]

Synthesis and in vitro study of new coumarin derivatives linked to nicotinonitrile moieties as potential acetylcholinesterase inhibitors

The appropriate pyridine-2(1H)-thiones were reacted with an equivalent amount of 5-(chloromethyl)-2-hydroxybenzaldehyde in ethanol in the presence of potassium hydroxide to give the corresponding 2-hydroxybenzaldehyde derivatives in excellent yields. The latter derivatives were taken as key synthons for the preparation of the target hybrids. Therefore, 2-hydroxybenzaldehydes were reacted with benzoylglycine in acetic anhydride in the presence of fused sodium acetate at 100°C for 6 hours to afford a new series of nicotinonitrile-coumarin hybrids. The in vitro acetylcholinesterase inhibitory activities were estimated for the new coumarins. The results were expressed as the inhibition percentage of the tested hybrids at concentration of 25 nM, compared to donepezil as a reference (inhibition percentage of 70.5). Coumarin hybrids linked to 6-(4-nitrophenyl) or 6-(4-chlorophenyl)-4-phenylnicotinonitrile exhibited more effective inhibitory activities than donepezil with inhibition percentages of 94.1 and 72.3, respectively. The new coumarins were tested for their free radical-scavenging capabilities against DPPH. Furthermore, some new coumarins were tested for in vitro cytotoxic activity against each MCF-10A, MCF-7, Caco2, and HEPG2. The new hybrids showed cytotoxicity in micromolar range (IC50 of 3.5-13.9 μM) against all tested cell lines. These results clearly demonstrated that the hybrids being tested are not cytotoxic at the concentration required to inhibit acetylcholinesterase effectively.

NOVEL SYNTHETIC ROUTE TO PYRIDINE-2(1H)-THIONES: UNEXPECTED PRODUCTS OF THE REACTION OF β-PHENETHYLIDENEMALONONITRILES WITH ARYLMETHYLENECYANOTHIOACETAMIDES

A novel synthesis of 3-cyanopyridine-2(1H)-thione derivatives utilizing arylmethylenecyanothioacetamides and β-phenethylidenemalononitriles as starting components is described.

CYCLIZATION OF NITRILES. XVII. METHODS FOR THE PRODUCTION OF 4,6-DIARYL-3-CYANO-2(1H)-PYRIDINETHIONES AND THEIR MASS-SPECTROMETRIC INVESTIGATION

The boundaries of the methods for the synthesis of 2(1H)-pyridinethiones were extended.The reactions of 3-aroyl-2-aryl- and 3-aroyl-2-aryl-1-bromo-1,1-dicyanopropanes with sodium and morpholinium hydrosulfides and thiourea and of arylidenecyanothioacetamides and 3-aryl-2,4,4-tricyano-3-butenethioamides with acetophenone, and 1-(1-piperidino)-1-phenylethylene, and also the reactions of monothiodibenzoylmethane and 1,3-diphenyl-1-(1-piperidino)-1-propene-3-one with cyanothioacetamide, leading to 4,6-diaryl-3-cyano-2(1H)-pyridinethiones, were investigated.The use of substituted cyanothioacetamides seems most promising.Mass-spectrometric investigation of the obtained thiones showed that the main direction in the dissociation of their molecular ions is the elimination of the H, HS., and CS particles with the formation of the thiazepinium and pyridinium ions and the corresponding radical-cation of pyrrole.

CYCLIZATION OF NITRILES. IX. SYNTHESES BASED ON 2-ARYL-3-AROYL-1,1-DICYANOPROPANES

2-Aryl-3-aroyl-1,1-dicyanopropanes and 2-aryl-3-aroyl-1-bromo-1,1-dicyanopropanes were synthesized from chalcones and malononitrile and were converted into 4,6-diaryl-2-bromo-3-cyanopyridines and 3-cyano-2(1H)-pyridinethiones.The 2-aryl-3-aroyl-1-bromo-1,1-dicyanopropanes proved convenient intermediates for the production of the corresponding cyclopropanes and other compounds.By their reaction with urea a new method was developed for the production of substituted 3-cyano-2(1H)-pyridinethiones.The 2-bromo-3-cyanopyridines contain a mobile bromine atom readily exchanged for the various nucleophilic residues of alcohols and amines and for iodide, and cyano and thiocyanato groups.The 3-cyano-2(1H)-pyridinethiones were used in the synthesis of 3-aminothienopyridines through the isolated 2-Z-methylthio-3-cyanopyridines.

SYNTHESIS AND SOME REACTIONS OF 3-CYANOPYRIDINE-2-THIONES

New method for the synthesis of 3-cyanopyridine-2-thiones by the reaction of δ-keto nitroles with sulfur and by condensation of chalcones or benzylideneacetone with cyanothioacetamide are given.The compounds obtained were used in various reactions for the preparation of alkylated products, disulfides, and condensed heterocycles, viz., thienopyridines and pyridothienopyrimidines.