Synthesis of tetrahydrobenzoxazepine acetals with electron-withdrawing groups on the nitrogen atom. Novel scaffolds endowed with anticancer activity against breast cancer cells

Abstract

Synthetic approaches that have led to (RS)-3-methoxy-N-substituded-1,2,3,5- tetrahydro-4,1-benzoxazepines with different electron-withdrawing groups, and (RS)-2-methoxy-N-trifluoroacetyl-2,3,4,5-tetrahydro-1,4-benzoxazepine are described. These novel synthons that were designed to be used as scaffolds for the preparation of new O,N-acetals as anticancer agents, unexpectedly proved to show antiproliferative activity against the MCF-7 breast cancer cell line. It has been found that substituents on the nitrogen atom have an influence on biological activity. In particular, the presence of a trifluoroacetyl moiety on the nitrogen atom leads to amides displaying interesting in vitro antitumour activities. Graphical Abstract. © 2004 Elsevier Ltd. All rights reserved.