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PDBsum entry 4ztn
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Transferase/transferase inhibitor
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PDB id
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4ztn
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References listed in PDB file
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Key reference
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Title
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Discovery and structure enabled synthesis of 2,6-Diaminopyrimidin-4-One irak4 inhibitors.
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Authors
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W.M.Seganish,
T.O.Fischmann,
B.Sherborne,
J.Matasi,
B.Lavey,
W.T.Mcelroy,
D.Tulshian,
J.Tata,
C.Sondey,
C.G.Garlisi,
K.Devito,
J.Fossetta,
D.Lundell,
X.Niu.
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Ref.
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Acs Med Chem Lett, 2015,
6,
942-947.
[DOI no: ]
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PubMed id
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Abstract
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We report the identification and synthesis of a series of aminopyrimidin-4-one
IRAK4 inhibitors. Through high throughput screening, an aminopyrimidine hit was
identified and modified via structure enabled design to generate a new, potent,
and kinase selective pyrimidin-4-one chemotype. This chemotype is exemplified by
compound 16, which has potent IRAK4 inhibition activity (IC50 = 27 nM) and
excellent kinase selectivity (>100-fold against 99% of 111 tested kinases),
and compound 31, which displays potent IRAK4 activity (IC50 = 93 nM) and good
rat bioavailability (F = 42%).
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