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PDBsum entry 4bbf
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References listed in PDB file
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Key reference
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Title
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Sar and in vivo evaluation of 4-Aryl-2-Aminoalkylpyrimidines as potent and selective janus kinase 2 (jak2) inhibitors.
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Authors
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T.Forsyth,
P.C.Kearney,
B.G.Kim,
H.W.Johnson,
N.Aay,
A.Arcalas,
D.S.Brown,
V.Chan,
J.Chen,
H.Du,
S.Epshteyn,
A.A.Galan,
T.P.Huynh,
M.A.Ibrahim,
B.Kane,
E.S.Koltun,
G.Mann,
L.E.Meyr,
M.S.Lee,
G.L.Lewis,
R.T.Noguchi,
M.Pack,
B.H.Ridgway,
X.Shi,
C.S.Takeuchi,
P.Zu,
J.W.Leahy,
J.M.Nuss,
R.Aoyama,
S.Engst,
S.B.Gendreau,
R.Kassees,
J.Li,
S.H.Lin,
J.F.Martini,
T.Stout,
P.Tong,
J.Woolfrey,
W.Zhang,
P.Yu.
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Ref.
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Bioorg Med Chem Lett, 2012,
22,
7653-7658.
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PubMed id
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Abstract
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We report the discovery of a series of 4-aryl-2-aminoalkylpyrimidine derivatives
as potent and selective JAK2 inhibitors. High throughput screening of our
in-house compound library led to the identification of hit 1, from which
optimization resulted in the discovery of highly potent and selective JAK2
inhibitors. Advanced lead 10d demonstrated a significant dose-dependent
pharmacodynamic and antitumor effect in a mouse xenograft model. Based upon the
desirable profile of 10d (XL019) it was advanced into clinical trials.
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