The Heck reaction for synthesis of novel kinase inhibitors.

Abstract

Reaction conditions were investigated and developed for coupling of acrylates with different properties. A total of seven acrylic thienopyrimidines were synthesized, five of which were synthesized directly with the Heck reaction. Testing of in vitro enzymatic inhibition activity indicated that the acrylic moieties has potential as very selective inhibitors, but due cis-trans isomerization problems, they are unsuitable for pharmaceutical use. Computer calculations indicate that the bioavailability properties of the acrylic moiety are improved, compared to the aryl moiety. Several acrylates were tested as a result of the project and the thesis postulates some new and stable, potential candidates with similar biological interactions.