SNAr and Palladium-Catalyzed Reactions of Deactivated Thiophene: Application to the Synthesis of Protein Farnesyltransferase Inhibitors

✍ Scribed by Sébastien Lethu; Joëlle Dubois

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 525 KB
• Volume: 2011
• Category: Article
• ISSN: 1434-193X
• DOI: 10.1002/ejoc.201100215

✦ Synopsis

Abstract

To investigate the influence of the 5‐thioether moiety of our previously identified hit thiophene compound upon protein farnesyltransferase inhibition, we synthesized a new library of 3‐(4‐chlorophenyl)‐4‐cyanothiophene‐2‐carboxylic derivatives through the application of aromatic nucleophilic substitutions benefiting from a sulfone‐based leaving group and by direct palladium‐catalyzed reactions on a thioalkylthiophene. This small library of ester derivatives and their corresponding acids was then evaluated for protein farnesyltransferase inhibitory activity; some library members exhibited promising submicromolar activities.