Abstract
Phosphatidylinositol-3-kinase alpha (PI3Kα) is an important target in cancer due to the deregulation of the PI3K/AKT signaling pathway in many tumors. In this study, we designed [3,5-d]-7-azaindole analogs as PI3Kα inhibitors through the fragment-growing strategy. By varying groups at the 3,5-positions of azaindole, we developed the SAR (Structure-activity relationship) and identified a series of potent PI3Kα inhibitors. Representative azaindole derivatives showed activity in a cellular proliferation and apoptosis assays. Moreover, B3 exhibited strong antiangiogenic effects on cancer cells.
Copyright © 2010 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiogenesis Inhibitors / chemical synthesis
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Angiogenesis Inhibitors / chemistry*
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Angiogenesis Inhibitors / therapeutic use
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Apoptosis*
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Breast Neoplasms / drug therapy
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Cell Line, Tumor
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Cell Movement
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Drug Evaluation, Preclinical
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / therapeutic use
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Female
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Humans
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Indoles / chemical synthesis
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Indoles / chemistry*
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Indoles / therapeutic use
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphoinositide-3 Kinase Inhibitors*
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Structure-Activity Relationship
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Sulfonamides / chemical synthesis
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Sulfonamides / chemistry*
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Sulfonamides / therapeutic use
Substances
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7-azaindole dimer
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Angiogenesis Inhibitors
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Enzyme Inhibitors
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Indoles
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Phosphoinositide-3 Kinase Inhibitors
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Sulfonamides