Synthesis and Structure−Activity Relationship of 2-Aminobenzophenone Derivatives as Antimitotic Agents

A new type of inhibitor of tubulin polymerization was discovered on the basis of the combretastatin molecular skeleton. The lead compounds in this series, compounds <BO>6</BO> and <BO>7</BO>, strongly inhibited tubulin polymerization in vitro and significantly arrested cells at the G<INF>2</INF>/M phase. Compounds <BO>6</BO> and <BO>7</BO> yielded 50- to 100-fold lower IC<INF>50</INF> values than did combretastatin A-4 against Colo 205, NUGC3, and HA22T human cancer cell lines as well as similar or greater growth inhibitory activities than did combretastain A-4 against DLD-1, HR, MCF-7, DU145, HONE-1, and MES-SA/DX5 human cancer cell lines. Structure−activity relationship information revealed that introduction of an amino group at the ortho position of the benzophenone ring plays an integral role for increased growth inhibition.