2016-2015
首页  科学研究  发表论文  2016-2015

A Facile and Efficient Synthesis of Hexahydro-1H-pyrido[2,3-b]indol-2-one Scaffolds via a Sequential Michael Addition/Amidation/Reductive Cyclization Process (Tetrahedron 2015, 71, 9483-9495)

Graphic Abstract

 

ABSTRACT

A new methodology was developed for the synthesis of hexahydro-1H-pyrido[2,3-b]indol-2-one scaffoldsviaa sequential Michael addition/amidation/reductive cyclization process.A wide variety ofproducts bearing ahexahydro-1H-pyrido[2,3-b]indol-2-one core with varying degrees of substitution around it, which is a key structural skeletonfound in a large number of biologically active natural products and pharmaceutical compounds, were obtained smoothlywith high efficiency (up to overall yield of 67%).Furthermore, their biological activities have been preliminarily demonstrated byin vitroevaluationagainsthumanprostate cancer cells PC-3, human lung cancer cells A549 andhuman leukemia cellsK562by the MTT-based assays, usingthe commercially available standard drugCisplatin as a positive control. These results suggested there is a trend that lipophilic groups improve the potency, and also suggested acarbonyl moiety located in the hexahydro-1H-pyrido[2,3-b]indol-2-one scaffolds isbeneficial for the activity.The results also demonstrated thatmost of the compounds showed considerable cytotoxicities to these three cell linesK562,A549 and PC-3, and thathexahydro-1H-pyrido[2,3-b]indol-2-one scaffoldsmay be potential leads for furtherantitumor activity screenings.