Synthesis of C-5 benzoyl and azido functionalized 2,2′-dithiobis-and 2,2′-diselenobis(1H-indoles) |
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Authors: | Li Sun J Ronald Rubin Alan J Kraker H D Hollis Showalter |
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Abstract: | Novel methods for the synthesis of C-5 benzoyl and azido analogues of 2,2′-dithiobis(1H-indole), 1, and 2,2′-diselenobis(1H-indole), 2, are described to further explore the structure activity relationships in this region of the molecule. Analogues 3-i displayed inhibitory activity (IC50 = 0.45-2.03 μ) toward the catalytic domain of the epidermal growth factor receptor tyrosine kinase that was equivalent to or better than that of unsubstituted compounds 1 and 2. The regiochemistry of Friedel-Crafts benzoylation onto 1 was determined by X-ray crystallography. To test the potential for compounds of this class to interact with the epidermal growth factor receptor tyrosine kinase via a sulfhydryl exchange mechanism, reaction of a 2,2′-dithiobis(1H-indole) with glutathione was carried out and the product characterized. |
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