Synthesis of 6-Aryl-pyrrolopyrimidines - Effect of ortho Substituents on EGFR Inhibitory Activity

Abstract

The goal of this project was to synthesise new and active epidermal growth factor receptor (EGFR) inhibitors which hopefully can be used in treatment of cancer. Seven new biological active pyrrolopyrimidines have been synthesised and characterised. This was accomplished by synthesising the pyrrolopyrimidine building block 3, followed by thermal amination and Suzuki coupling. The main focus has been on introducing new substituents in the ortho position of the 6-aryl group. In addition, metabolic stability of the target molecules has been attempted improved by introducing substituents like CHF2, CF3 and pyridine.

In general, a good activity towards EGFR-TK inhibition was accomplished. The 6-aryl moieties identified may be used in combination with other potency inducing groups to hopefully enhance the activity.