Monastrol was the first specific but moderate inhibitor of the mitotic kinesin Eg5 to be identified. It proved to be useful for studies of cell division and is thought to have anticancer potential. We have synthesized a small chemical library of monastrol analogues and tested them for Eg5 inhibition in vitro and for arresting mitosis of cultured cells. We found that dimethylenastron (1) is more than 100‐times more potent than monastrol in both cases.

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Human Eg5 is a mitotic kinesin that is essential for bipolar spindle formation and maintenance during mitosis. Recently, the discovery of compounds that inhibit Eg5 and cause mitotic arrest has attracted great interest, due to their potential use as the next generation of antimitotics. Here, we present the synthesis and biological investigation of 3,4-dihydrophenylquinazoline-2(1H)-thiones as selective and potent Eg5 inhibitors.

A paramount role in carcinogenesis is played by the tumour‐suppressor protein p53. In the case of DNA damage, it leads to cell‐cycle arrest or apoptosis. p53 activity is often reduced due to the overexpression of its main regulator, the Mdm2 protein. The discovery of small molecules, such as 1, that are able to inhibit the interaction between p53 and Mdm2 opens up new possibilities for the therapy of malignant diseases.