Synthesis and Biological Evaluation of Thienopyrrolizines, a New Family of CDK/GSK-3 Inhibitors

Abstract

Fifteen new thieno[2,3-b]- and thieno[3,4-b]pyrrolizines were synthesized and tested against two protein kinases, CDK1/cyclin B and GSK-3. Among these compounds, 3-(3-hydroxy-4-methoxyphenyl)-8H-thieno[2,3-b]pyrrolizin-8-one 4g was identified as a moderate inhibitor of these kinases. Its molecular modeling study brought to the fore the pivotal role of the 2-methoxyphenol grouping and the interest in replacing it by bioisosteric moieties in future pharmacomodulations.

Keywords: :

• Thieno[2,3-b]pyrrolizines
• Thieno[3,4-b]pyrrolizines
• Protein kinases
• CDK1/cyclin B
• GSK-3
• Phosphorylation