Synthesis of novel 3′-spirocyclic-oxindole derivatives and assessment of their cytostatic activities

Abstract

The synthesis of some novel 3′-spirocyclic-oxindole compounds, based on the spiro[indole-3,5′-isoxazolidin]-2(1 H)-one, the 2′ H-spiro[indole-3,6′-[1,3]oxazinane]-2,2′(1 H)-dione and the 2′ H-spiro[indoline-3,3′-pyrrolo[1,2- c][1,3′]oxazine]-1′,2(1 H)-dione heterocyclic structures, is described. These compounds were prepared from methyl α-(2-nitrophenyl)acrylate via [1,3]-dipolar cycloaddition reactions with two acyclic nitrones and one cyclic nitrone followed by reduction of the cycloadducts and then treatment with triphosgene. Two of these compounds showed significant cytostatic activity on three cancer cell lines with GI 50 values of 2.6–4.1 μM on the human breast cancer cell line, MCF-7.