A variety of N-[(4,6-diaryl-3-pyridinecarbonitrile)-2-yl] amino acid esters 2-4 were synthesized through the reaction of 2-bromo-3-pyridinecarbonitriles 1 with the appropriate alpha-amino acid ester hydrochloride in refluxing dioxane in the presence of triethylamine as dehydrohalogenating agent. Similarly, N'-glycylglycine analogues 5 were obtained through the reaction of 1 with the dipeptide ester. On the other hand, attempts were made towards the construction of amino acid derivatives 7 through the reaction of 1 with aqueous solution alpha-amino acids 6 in refluxing pyridine, but were unsuccessful, and instead the unexpected 2-amino-3-pyridinecarbonitriles 8 were isolated. The fluorescence properties of the newly synthesized pyridines 2-5 were evaluated. Some of the prepared compounds show considerable antibacterial activity.
Various 2-propen-1-ones react with malononitrile under basic catalysis to yield cyclohexanol derivatives. This happens via double Michael reaction of malononitrile with propenone, followed by intramolecular cyclization under basic conditions (1-3). On the other hand, reaction of 1,3-diaryl-2-propen-1-ones with malononitrile in the presence of a sufficient amount of alkoxide anion led to the formation of 2-alkoxy-3-cyanopyridines (1-4). Numerous condensed pyridine carbonitrile systems were obtained under similar conditions by the reaction of malononitrile with various a,b-unsaturated ketones (5-9). In the present work, the reaction of 1-(2-thienyl or furanyl)-3-(2-hydroxyphenyl)-2-propen-1-ones with malononitrile in the presence of a sufficient amount of alkoxide anion was investigated. The hydroxyl group might behave as an active nucleophilic centre, affording condensed 5H-[1]benzopyrano[3,4-c]pyridine derivatives. The synthesis of this condensed heterocyclic system is interesting because of the potential biological activities associated with its structure, such as antipsychotic dopamine D 4 receptor antagonist (10), cancer chemopreventive (11), antibacterial (including anti-tubercular) (12), antirheumatic (13), against Alzheimer disease, Parkinson's disease, anxiety, depression, allergic responses and sedation (14). On the other hand, polysubstituted pyridines, especially the 3,5-pyridinedicarbonitriles, are interesting as antioxidants and NADH co-enzyme In continuation of our search for new substituted pyridine based anti-inflammatories, reaction of 1-(2-thienyl or furanyl)-3-(2-hydroxyphenyl)-2-propen-1-ones (1) with malononitrile in alcoholic KOH solution afforded a mixture of 4-alkoxy-2-(2-thienyl or furanyl)-5H-[1]benzopyrano[3,4-c]pyridine-5-ones (2) and 2-alkoxy-4-amino-6-(2-thienyl or furanyl)-3,5-pyridinedicarbonitriles (3). Some of the synthesized compounds were evaluated for their anti-inflammatory and analgesic activities compared to diclofenac potassium as positive control. Detailed synthesis, spectroscopic and toxicity data are reported.
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