Synthesis and mechanism of action of novel pyrimidinyl pyrazole derivatives possessing antiproliferative activity.
Ohki H, Hirotani K, Naito H, Ohsuki S, Minami M, Ejima A, Koiso Y, Hashimoto Y.
Pyrimidinyl pyrazole derivatives 1-4, prepared as a new scaffold of an anti-tumor agent, showed antiproliferative activity against human lung cancer cell lines and inhibited tubulin polymerization. Furthermore, it was found that compound 2 bound at the colchicine site on tubulin, but the tubulin binding pattern was different from that of colchicine. Here, we describe the synthesis of the derivatives and the differences of the action mechanism on tubulin polymerization inhibition between compound 2 and colchicine.