A spirocyclic oxindole analogue: Synthesis and antitumor activities

A new synthesis of spirocyclic oxindole analogue spiro[piperidine-4,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one 1 is described. The key steps involve dialkylation of arylacetonitrile and cyclization of the azaoxindole ring by an intramolecular Buchwald Hartwig amidation of carboxylic amide and aryl chloride. A small library was obtained by reductive amination of 1 with various aldehydes and was screened against human lung cancer cell A549, human liver cancer cell BEL7402, and human colon cancer cell HCT-8. The results show that most of the library compounds 2 have some inhibitory activities. 2-(Trifluoromethoxy) benzylic substituted spirocyclic azaoxindole 2e was identified as a nanomolar inhibitor against human lung cancer cell A-549 (IC50 = 50 nmol/L). (C) 2011 Da Wei Teng. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.