Synthesis,Crystal Structure and Anticancer Activities of Tetrahydropyrido[4,3‐d]dihydropyrimidine‐2‐thiones

A new series of tetrahydropyrido4,3‐d]dihydropyrimidine‐2‐thiones ( 3a–3x ) were designed and synthesized. Their structures were confirmed by ¹H NMR, IR, MS and elemental analysis, and the conformation of compound 3j was confirmed by X‐ray diffraction. Preliminary bioassays indicated that most of the target compounds presented good antiproliferative activities against leukemic K562 cells, ovarian cancer HO‐8910 cells and liver cancer SMMC‐7721 cells in vitro. Among them the compounds 3i and 3m afford the best activity, the IC₅₀ of them were 3.22 and 3.65 µg/mL against leukemic K562 cells, respectively, which were lower than the anticancer drug of clinical practice 5‐FU (IC₅₀=8.56 µg/mL). Preliminary mechanism of action studies revealed that compound 3i caused DNA fragmentation and activated caspase‐3/7 in leukemic K562 cells.