Synthesis of Novel DPPH-Free Radical Scavenger Se-Containing Fused Chalcogenophenes: 2-Alkyl-7-Cyano-4-Imino-3-Phenyl-6-(pyrrolidin-1-yl)-3,4-Dihydroselenopheno[3,2-d]Pyrimidines

A straightforward and effective strategy for the synthesis of novel 7-cyano-4-imino-3-phenyl-6-(pyrrolidin-1-yl)-2-substituted-3,4-dihydroselenopheno[3,2-d]pyrimidines have been accomplished through a base-promoted cascade addition/cyclization sequence employing phenyl isothiocyanate followed by the S-alkylation of the obtained fused Se-containing heterocyclic framework with various alkyl halides. Free radical scavenging activity of the synthesized selenium-containing structures was studied against DPPH, as well. Antioxidant activities as IC50 values were ranged from 12.19 to 91.08 mu M. Unfused 3-amino-2,4-dicyano-5-(pyrrolidin-1-yl)selenophene was much more powerful antioxidant agent than ascorbic acid. Moreover, the promising antioxidant potentials were observed with selenopheno[3,2-d]pyrimidines. Taking into account the best antioxidant activity of S-benzylated derivative amongst pyrimidine-fused heterocycles and significant relationship between antioxidant activity of compounds and many of their biological potencies, using benzyl halides bearing electron donating groups on phenyl ring can probably improve their antioxidant capacities to make them more effective anti-cancer, anti-diabetic, anti-inflammatory and anti-neurodegenerative agents.

Automated summary

A series of novel selenium-containing compounds, 7-cyano-4-imino-3-phenyl-6-(pyrrolidin-1-yl)-2-substituted-3,4-dihydroselenopheno[3,2-d]pyrimidines, were successfully synthesized through a base-promoted cascade addition/cyclization sequence. The synthesized compounds showed promising antioxidant activity, with IC50 values ranging from 12.19 to 91.08 μM. Among the compounds, the unfused 3-amino-2,4-dicyano-5-(pyrrolidin-1-yl)selenophene exhibited higher antioxidant activity than ascorbic acid. The benzylated derivative of the pyrimidine-fused heterocycles showed the best antioxidant activity, suggesting the potential for these compounds to be used as effective anti-cancer, anti-diabetic, anti-inflammatory, and anti-neurodegenerative agents.