作者:T Benneche、P Strande、R Oftebro、K Undheim
DOI:10.1016/0223-5234(93)90014-6
日期:1993.1
5-Halo-N(1)-substituted 2(1H)-pyrimidinones have the ability to cause reversible arrest of mitosis during metaphase, Highly active compounds have a heteroatom (O, S or N) in the beta-position of the N(1)-carbon chain which is further substituted by an aryl group. In vitro data have been provided. It is suggested that reversible metaphase inhibitors can be used as synchronizing agents of cell-cycles by applying them in a sequential manner when a phase-specific cytotoxic drug is used in the treatment of diseases caused by uncontrolled rapidly proliferating cells. The active compounds are prepared from 2-pyrimidinones by alkylation reactions. The key reactants are alpha-chloroalkyl ethers, sulfides and amides; methods for their syntheses have been described.