Beyond the classical chiral resolution: Modern enantioselective synthetic strategies used in the preparation of new chiral kinase inhibitors including drugs for autoimmune diseases and antitumoral drugs

Abstract

Kinase inhibitors is one of the most approved class by FDA in this century. These proteins are versatile targets that have a huge impact in several pharmacotherapy including against cancer, autoimunne and rare diseases. Thus, the number of patents that aim these targets are increasing and is becoming harder to be innovative in this field. Furthermore, the design of ATP-competitive inhibitors is the major strategy used to develop new kinase inhibitors and there are few regions in the ATP cleft or around it, which are generally explored by the commercially available inhibitor drugs. In this way in this review, we focused in the use of modern enantioselective strategies that were carried out in the last years to prepare new chiral kinase inhibitors as an emerging field that resulted in several new potent innovative approved drugs. Also we suggested new trends in this modern relevant topic and analyzed kinase-drug complexes highlighting the interactions that support the importance of the stereochemistry.