A new four-component reaction involving the Michael addition and the Gewald reaction, leading to diverse biologically active 2-aminothiophenes

作者：Thomas Joice; Jana Sampad; Sonawane Mahendra; Fiey Bert; Balzarini Jan; Liekens Sandra^*; Dehaen Wim^*

来源：Organic and Biomolecular Chemistry, 2017, 15(18): 3892-3900.

DOI：10.1039/c7ob00707h

The Gewald three-component reaction yielding highly substituted 2-aminothiophene heterocycles has been known for a long time and holds an extraordinary potential in the pharmaceutical industry. Herein, we describe a four-component reaction initiated by the conjugate addition of different indole derivatives to alpha,beta-unsaturated carbonyl compounds. This is followed by an in situ Gewald three-component reaction which results in the formation of a compound containing an indole and a 2-aminothiophene moiety separated by a methylene spacer. We also examined the impact of the use of other nucleophilic components such as pyrrole derivatives on this MG-4CR (Michael-Gewald four component reaction). All these synthesized compounds were tested for anti-proliferative activity and three of them showed activity in the nanomolar range.

• 出版日期2017-5-14
• 单位河北医科大学