Organocatalytic [3 + 2] Cycloaddition Reaction: Synthesis of Fully Decorated Sulfonyl-1,2,3-Triazolyl Pyrimidines as Potent Anticancer and EGFR Inhibitors
Jagan Mohan Reddy Velidandla, Shiva Kumar Koppula
Abstract
A general strategy was developed for the synthesis of new fully decorated sulfonyl1,2,3-triazolyl pyrimidines (6a–6j and 8a–8f) from 2-((6-methyl-2-(methylsulfonyl)pyrimidin-4-yl)sulfonyl)-1-(4-nitrophenyl)ethanone and several azides in the presence of catalytic amounts of organocatalyst. Ramachary OrgAKC reaction of β-ketosulfone (4) acts as an internal alkyne as reported for the synthesis of sulfonyl-1,2,3-triazolyl pyrimidines at 80 °C in good to excellent yields of products in the presence of catalytic amounts of pyrrolidine (10 mol %). In vitro anticancer activity of all these derivatives revealed that six compounds like 6d, 6e, 6g, 6h, 8c, and 8d were active against three human cancer cell lines like breast carcinoma, cervical carcinoma, and alveolar carcinoma. In specific, compounds 6g and 6h showed superior activity against tested cell lines compared to the standard drug erlotinib. Later, the results of inhibitory assay of potent compounds 6d, 6e, 6g, 6h, 8c, and 8d against the tyrosine kinase epidermal growth factor receptor (EGFR) revealed that compounds 6g and 6h showed more potency than the reference drug erlotinib.