Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8993384 | Il Farmaco | 2005 | 6 Pages |
Abstract
A convenient synthesis of novel 8-sulfonyl-1,3-dioxo-4-methyl-2,3-dihydro-1H-pyrrolo[3,4-c]quinolines is described. As key steps to assemble the target molecular scaffold, our method features (a) Pfitzinger reaction of isatin-5-sulfonate 1 with methyl 3-oxo-3-phenylpropanoate, (b) formation of 1-(1H-pyrazol-4-yl)-1H-pyrrole-2,5-dione intermediate 5, and (c) reaction of sulfinic acid 9 with acrylate or methylacrylate leading to the corresponding sulfonyl propionates. Two compounds, ester 11 and morpholide 13, have been identified as potent inhibitors of caspase-3 with IC50Â =Â 6Â nM. Our primary data suggest noncompetitive and reversible character of caspase-3 inhibition.
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Authors
Dmitri V. Kravchenko, Volodymyr M. Kysil, Sergey E. Tkachenko, Sergey Maliarchouk, Ilya M. Okun, Alexandre V. Ivachtchenko,