Synthesis and Biological Evaluation of Furo[2,3-d]pyrimidines as EGFR Tyrosine Kinase Inhibitors

Abstract

The work performed in this master s thesis has contributed to a larger ongoing study on the development of new epidermal growth factor (EGFR) tyrosine kinase inhibitors, intended for use in cancer chemotherapy.

The primary goal of this thesis has been the synthesis of new 4-amino-6-aryl substituted furo[2,3-d]pyrimidines and the biological evaluation of their potency as EGFR tyrosine kinase inhibitors. The effect of substitutions in the 4-amino fragment has been the focal point of the study. In total 10 target compounds have been synthesized and tested for enzymatic activity, and several compounds were shown to be highly potent.

Due to considerable challenges associated with furan synthesis, three synthetic routes have been employed and evaluated in this thesis. Key problems in the classical literature procedure have been identified and attempts at improvement of problematic steps have been made. A new synthetic strategy, based on the Sonogashira cross-coupling reaction has also been investigated.