Design and synthesis of two cytotoxic analogs of the novel pyrrolo[1′,2′:1,2][1,4]diazepin [7,6-b]indol-5(6h)-one nucleus

Tsotinis, A., Vlachou, M., Kiakos, K., Hartley, J.A. and Thurston, D.E. (2003) Design and synthesis of two cytotoxic analogs of the novel pyrrolo[1′,2′:1,2][1,4]diazepin [7,6-b]indol-5(6h)-one nucleus. Chemistry Letters, 32 (6). pp. 512-513. 10.1246/cl.2003.512.

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DOI: 10.1246/cl.2003.512

Abstract

The design and synthesis of the two cytotoxic derivatives 15 and 16 of the novel pyrrolo[1′,2′:1,2][1,4]diazepin[7,6-b]indol-5(6H)-one nucleus is described. Readily available methyl 2-indolecarboxylates 5 and 6 are nitrosated with NaNO2 in AcOH to give the analogs 7 and 8, which are then oxidized with KMnO4 in aq. NaOH to provide the 3-NO2 acids 9 and 10. These, in turn, are subjected to amidation with (2S)-pyrrolidine-2-carboxaldehyde diethyl thioacetal in the presence of EDCI and HOBt and then to a 7-exo-trig cyclization reaction to give the target molecules 15 and 16. The new analogs were evaluated in the human leukemic K 562 cell line and were shown to have micromolar potency.

Item Type:Article
Departments, units and centres:Department of Pharmaceutical and Biological Chemistry > Department of Pharmaceutical and Biological Chemistry
ID Code:2918
Journal or Publication Title:Chemistry Letters
Deposited By:Library Staff
Deposited On:08 Mar 2012 16:32
Last Modified:08 Mar 2012 16:32

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