Synthesis and biological evaluation of sulfonamide analogues of the phosphatidylinositol 3-kinase inhibitor ZSTK474

Synthesis and biological evaluation of sulfonamide analogues of the phosphatidylinositol 3-kinase inhibitor ZSTK474

[Display omitted] Replacement of one of the morpholine groups of the phosphatidylinositol 3-kinase (PI3K) inhibitor ZSTK474 (1) with sulfonamide containing substituents produced a new class of active and potent PI3Kα inhibitors. Solubility issues prevented all but the 6-amino derivative 17 from bein...

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Veröffentlicht in:Bioorganic & medicinal chemistry 2017-10, Vol.25 (20), p.5859-5874
Hauptverfasser: Gamage, Swarna A., Giddens, Anna C., Tsang, Kit Y., Flanagan, Jack U., Kendall, Jackie D., Lee, Woo-Jeong, Baguley, Bruce C., Buchanan, Christina M., Jamieson, Stephen M.F., Shepherd, Peter R., Denny, William A., Rewcastle, Gordon W.
Format: Artikel
Sprache:eng
Schlagworte:
Cell Line, Tumor
Enzyme Activation - drug effects
Humans
Molecular Structure
p110α
Phosphatidylinositol 3-kinase
Phosphatidylinositol 3-Kinases - antagonists & inhibitors
PI3K
Solubility
Sulfonamides - chemical synthesis
Sulfonamides - chemistry
Sulfonamides - pharmacology
Triazines - chemistry
Triazines - pharmacology
ZSTK474
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Zusammenfassung:[Display omitted] Replacement of one of the morpholine groups of the phosphatidylinositol 3-kinase (PI3K) inhibitor ZSTK474 (1) with sulfonamide containing substituents produced a new class of active and potent PI3Kα inhibitors. Solubility issues prevented all but the 6-amino derivative 17 from being evaluated in vivo, but the clear activity of this compound demonstrated that this class of PI3K inhibitor shows great promise.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2017.09.025