Synthesis and anticancer evaluation of some novel N,O,S heterocyclic compounds pendant to 3‐methyl‐5‐cyano‐6‐(3,4‐dimethoxyphenyl)pyrimidine and other related fused pyrimidines

Abstract

The key starting compound 5-cyano-6-(3,4-dimethoxyphenyl)-2-thiouracil (1) was synthesized and allowed to undergo electrophilic substitution with methyl iodide to give the corresponding 6-(3,4-dimethoxyphenyl)-4-oxo-2-thioxo-1,2,3,4-tetrahydro-pyrimidine-5-carbonitrile (2). Nucleophilic substitution on compound 2 with hydrazine hydrate led to the corresponding 2-hyrazinopyrimidone intermediate 3. Compound 3 underwent several substitution and cyclization reactions with β-ketoester, β-ketone, alkyl halides, arylisothiocyanate, or aromatic aldehydes followed by cyclization reactions to give the corresponding N,O,S heterocyclic compounds incorporated into pyrimidine moiety and/or the related S-triazino [3,4-b]pyrimidine derivatives 4-18. Anticancer evaluation of some representative examples of newly synthesized compounds was carried out against MCF-7, HCT116 cell lines. Some of the newly synthesized compounds showed significant activity.

Design, Synthesis and Antibacterial Activity of Novel Pyrimidine‐Containing 4H‐Chromen‐4‐One Derivatives**

“…Intermediates 1 were prepared according to the reported methods. [26,41,42] General synthesis procedure for intermediate 1.…”

“…Based on the previous reported method [41,42], the ethyl cyanoacetate (5 mmol), substituted aromatic aldehyde (5 mmol), thiourea (5 mmol) and anhydrous K 2 CO 3 (7.5 mmol) were added in ethanol (50 mL) then re uxed for about 4-6 h, after the reaction was completed (monitoring the reaction by TLC), mixture was cooled to room temperature and diluted with ice water, a large amount of solids precipitated as the pH was adjusted with glacial acetic acid to weak acidity, solids were ltered and dried with suction, recrystallized with absolute ethanol to After the solution had been stirred at room temperature for 0.5-1 h, the different dibromoalkane (2 mmol) was added and reaction system continued at room temperature for 10 h. Mixture was dispersed in 50 mL ice water when reaction was completed (reaction was monitored by TLC) so a white solid was precipitated, sample was passed through a suction lter to remove the liquid, solid was continuously stirred in a mixed solution of 30 mL petroleum ether and ethyl acetate for 3-4 hours, then ltered and dried under reduced pressure to obtain Intermediate 3.…”

“…Pyrimidine is an important class of heterocyclic compounds with wide applications in medicine and pesticides research due to their remarkable biological and pharmacological properties, such as antibacterial [23][24][25], antiviral [26,27], insecticide [28,29], anticancer [30,31], antimalaria [32], herbicida [33] and other biological activities [34]. In 2019, Zhang reported a series of derivatives containing pyrimidine ethers were synthesized, which have a good control effect on cucumber downy mildew [35].…”

Design, Synthesis and Antibacterial Activity of Novel Pyrimidine-Containing 4H-Chromen-4-one Derivatives

“…Based on the previous reported method [41,42], the ethyl cyanoacetate (5 mmol), substituted aromatic aldehyde (5 mmol), thiourea (5 mmol) and anhydrous K 2 CO 3 (7.5 mmol) were added in ethanol (50 mL) then re uxed for about 4-6 h, after the reaction was completed (monitoring the reaction by TLC), mixture was cooled to room temperature and diluted with ice water, a large amount of solids precipitated as the pH was adjusted with glacial acetic acid to weak acidity, solids were ltered and dried with suction, recrystallized with absolute ethanol to…”