Palladium-catalyzed synthesis and nucleotide pyrophosphatase inhibition of benzo[4,5]furo[3,2-b]indoles

Abstract

A two-step palladium-catalyzed procedure based on Suzuki–Miyaura cross coupling, followed by a double Buchwald–Hartwig reaction, allows for the synthesis of pharmaceutically relevant benzo[4,5]furo[3,2-b]indoles in moderate to very good yield. The synthesized compounds have been analyzed with regard to their inhibitory activity (IC50) of nucleotide pyrophosphatases h-NPP1 and h-NPP3. The activity lies in the nanomolar range. The results were rationalized based on docking studies.

Keywords

• buchwald–hartwig reaction
• cyclization
• n-heterocycles
• palladium
• suzuki–miyaura reaction