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

• DOI: 10.1016/j.tet.2004.09.072
• Publication Date: 2004-10-12T12:41:28Z
• Authors: Mónica Díaz-Gavilán; Fernando Rodrígue...; José A. Gómez-Vidal; Juan A. Marchal; Antonia Aránega; Miguel Á. Gallo; Antonio Espinosa; Joaquín M. Campos
• Keywords: Synthon; Nitrogen atom; Moiety; Polar effect; Cancer cell lines

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.