60847-68-9Relevant academic research and scientific papers
Chalcone-inspired rA1/A2A adenosine receptor ligands: Ring closure as an alternative to a reactive substructure
Matthee, Chrisna,Terre’Blanche, Gisella,Janse van Rensburg, Helena D.,Aucamp, Janine,Legoabe, Lesetja J.
, p. 416 - 437 (2021/12/30)
Over the past few years, great progress has been made in the development of high-affinity adenosine A1 and/or A2A receptor antagonists—promising agents for the potential treatment of Parkinson's disease. Unfortunately, many of these compounds raise structure-related concerns. The present study investigated the effect of ring closures on the rA1/A2A affinity of compounds containing a highly reactive α,β-unsaturated carbonyl system, hence providing insight into the potential of heterocycles to address these concerns. A total of 12 heterocyclic compounds were synthesised and evaluated in silico and in vitro. The test compounds performed well upon qualitative assessment of drug-likeness and were generally found to be free from potentially problematic fragments. Most also showed low/weak cytotoxicity. Results from radioligand binding experiments confirm that heterocycles (particularly 2-substituted 3-cyanopyridines) can replace the promiscuous α,β-unsaturated ketone functional group without compromising A1/A2A affinity. Structure–activity relationships highlighted the importance of hydrogen bonds in binding to the receptors of interest. Compounds 3c (rA1Ki?=?16?nM; rA2AKi?=?65?nM) and 8a (rA1Ki?=?102?nM; rA2AKi?=?37?nM), which both act as A1 antagonists, showed significant dual A1/A2A affinity and may, therefore, inspire further investigation into heterocycles as potentially safe and potent adenosine receptor antagonists.
A Facile Synthesis of 6-Alkoxy-2,4-diaryl-5-cyanopyridine
Al-Arab, Mohammad M.
, p. 1665 - 1673 (2007/10/02)
A new synthesis of substituted pyridine is reported.The base catalyzed reaction of substituted chalcones with malononitrile using sodium ethoxide in ethanol at room temperature afforded 2,4-diaryl-5-cyano-6-ethoxypyridine.Similarly, 2,4-diaryl-5-cyano-6-methoxypyridine have been prepared in presence of sodium methoxide in methanol as a catalyst.
A NOVEL SYNTHETIC ROUTE TO PHENYL-SUBSTITUTED PYRIDINES; SYNTHESIS OF BENZOPYRANOPYRIDINES, BENZOTHIOPYRANOPYRIDINES AND PYRIDOBENZOTHIAZINES(1-AZAPHENOTHIAZINES)
Tyndall, D. V.,Al Nakib, T.,Meegan, M. J.
, p. 2703 - 2706 (2007/10/02)
Reaction of 1,3-diphenylpropenone with malononitrile in base affords 1,4-diphenyl-2-methoxypyridine-3-carbonitrile.This reaction has been applied to a general synthesis of phenyl-substituted benzopyranopyridines, benzothiopyranopyridines and pyridobenzothiazines(1-azaphenothiazines).
CYCLIZATION OF NITRILES. IX. SYNTHESES BASED ON 2-ARYL-3-AROYL-1,1-DICYANOPROPANES
Shestopalov, A. M.,Promonenkov, V. K.,Sharanin, Yu. A.,Rodinovskaya, L. A.,Sharanin, S. Yu.
, p. 1382 - 1401 (2007/10/02)
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.
