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Herein, a rapid and highly efficient method for the synthesis of a new series of pyrimidine derivatives was demonstrated. The strategy was emanated from the reaction of hydrazinyl pyrimidine derivative (1) with different electrophilic species such as ethyl acetoacetate, ethyl 4,4,4‐trifluoro acetoacetate, and phenyl isothiocyanate following cyclocondensation mechanism to afford the corresponding derivatives (2‐6). Furthermore, condensation of hydrazine derivative (1) with different carbonyl compounds via conventional heating and microwave irradiation conditions was employed as a source of Schiff base derivatives bearing pyrimidine moiety (7‐12). The structural features of all newly synthesized compounds were characterized by elemental and spectroscopic evidences. Some of the synthesized compounds were evaluated for in vitro cytotoxicity. The preliminary screening results showed that most of the tested compounds have moderate cytotoxic activity against HepG2 and HCT‐116 cell lines. Finally, a molecular docking study was conducted to reveal the probable interaction with the thymidylate synthase enzyme. [ABSTRACT FROM AUTHOR]

A new series of 6-aryl-5-cyano thiouracil derivatives were synthesized. Cyanouracil1was condensed with monochloroacetic acid and different aldehydes to give thiazolopyrimidine2. On the other hand, treatment of cyanouracil1with 2-chloro-N-substituted-phenylac etamide afforded4. Hydrazinolysis of6afforded the hydrazino derivatives7which upon reaction with different electrophilic reagents such as acetic anhydride, benzoyl chloride, and carbon disulfide yielded pyrimidine derivatives8–15. Some of the new derivatives were explored for their antimicrobial activities. Compounds7and9have a promising activity, relatively equipotent to the reference drug. All of the new synthesized compounds were testedin vitrofor their antiproliferative activities against HePG-2 and MCF-7 cell lines. Compounds7,9, and2ddisplayed potent growth inhibitory effect toward the two cell lines more than the standard drug 5-FU. Furthermore, a docking study of the most active compounds was performed with thymidylate synthase enzyme. [ABSTRACT FROM AUTHOR]