doi: 10.1016/j.bmcl.2010.03.046.
Epub 2010 Mar 12.
Identification of GNE-477, a potent and efficacious dual PI3K/mTOR inhibitor
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- PMID: 20346656
- DOI: 10.1016/j.bmcl.2010.03.046
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Identification of GNE-477, a potent and efficacious dual PI3K/mTOR inhibitor
Bioorg Med Chem Lett.
.
Abstract
Efforts to identify potent small molecule inhibitors of PI3 kinase and mTOR led to the discovery of the exceptionally potent 6-aryl morpholino thienopyrimidine 6. In an effort to reduce the melting point in analogs of 6, the thienopyrimidine was modified by the addition of a methyl group to disrupt planarity. This modification resulted in a general improvement in in vivo clearance. This discovery led to the identification of GNE-477 (8), a potent and efficacious dual PI3K/mTOR inhibitor.
Copyright 2010 Elsevier Ltd. All rights reserved.
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