Synthesis and Biological Activity of C-8 Fluoroaryl Substituted Pyrimidine Linked-Pyrrolobenzodiazepine Conjugates

Synthesis of C-8 fluoroaryl substituted pyrimidine linked-PBD conjugates are described. The compounds are prepared with varying degrees of linker length in order to probe the structural requirements for optimal in vitro antitumour activity. These compounds have been tested against a panel of 60 human cancer cell lines, and it is demonstrated that compound 5b with four carbon spacer exhibited promising in vitro anticancer activity in comparison to the other analogues (5a and 5c).