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Synthesis of C‐5 benzoyl and azido functionalized 2,2′‐dithiobis‐and 2,2′‐diselenobis(1 H ‐indoles)
Author(s) -
Sun Li,
Rubin J. Ronald,
Kraker Alan J.,
Showalter H. D. Hollis
Publication year - 1997
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570340505
Subject(s) - chemistry , indole test , stereochemistry , regioselectivity , molecule , combinatorial chemistry , catalysis , organic chemistry
Novel methods for the synthesis of C‐5 benzoyl and azido analogues of 2,2′‐dithiobis(1 H ‐indole), 1, and 2,2′‐diselenobis(1 H ‐indole), 2, are described to further explore the structure activity relationships in this region of the molecule. Analogues 3‐i displayed inhibitory activity (IC 50 = 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(1 H ‐indole) with glutathione was carried out and the product characterized.