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PDBsum entry 4i5c
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References listed in PDB file
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Key reference
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Title
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Novel triazolo-Pyrrolopyridines as inhibitors of janus kinase 1.
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Authors
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C.A.Hurley,
W.S.Blair,
R.J.Bull,
C.Chang,
P.H.Crackett,
G.Deshmukh,
H.J.Dyke,
R.Fong,
N.Ghilardi,
P.Gibbons,
P.R.Hewitt,
A.Johnson,
T.Johnson,
J.R.Kenny,
P.B.Kohli,
J.J.Kulagowski,
M.Liimatta,
P.J.Lupardus,
R.J.Maxey,
R.Mendonca,
R.Narukulla,
R.Pulk,
S.Ubhayakar,
A.Van abbema,
S.I.Ward,
B.Waszkowycz,
M.Zak.
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Ref.
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Bioorg Med Chem Lett, 2013,
23,
3592-3598.
[DOI no: ]
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PubMed id
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Abstract
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The identification of a novel fused triazolo-pyrrolopyridine scaffold, optimized
derivatives of which display nanomolar inhibition of Janus kinase 1, is
described. Prototypical example 3 demonstrated lower cell potency shift, better
permeability in cells and higher oral exposure in rat than the corresponding,
previously reported, imidazo-pyrrolopyridine analogue 2. Examples 6, 7 and 18
were subsequently identified from an optimization campaign and demonstrated
modest selectivity over JAK2, moderate to good oral bioavailability in rat with
overall pharmacokinetic profiles comparable to that reported for an approved
pan-JAK inhibitor (tofacitinib).
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