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PDBsum entry 4rg0
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Transferase/transferase inhibitor
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PDB id
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4rg0
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References listed in PDB file
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Key reference
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Title
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Finding the perfect spot for fluorine: improving potency up to 40-Fold during a rational fluorine scan of a bruton'S tyrosine kinase (btk) inhibitor scaffold.
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Authors
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Y.Lou,
Z.K.Sweeney,
A.Kuglstatter,
D.Davis,
D.M.Goldstein,
X.Han,
J.Hong,
B.Kocer,
R.K.Kondru,
R.Litman,
J.Mcintosh,
K.Sarma,
J.Suh,
J.Taygerly,
T.D.Owens.
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Ref.
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Bioorg Med Chem Lett, 2015,
25,
367-371.
[DOI no: ]
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PubMed id
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Abstract
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A rational fluorine scan based on co-crystal structures was explored to increase
the potency of a series of selective BTK inhibitors. While fluorine substitution
on a saturated bicyclic ring system yields no apparent benefit, the same
operation on an unsaturated bicyclic ring can increase HWB activity by up to
40-fold. Comparison of co-crystal structures of parent molecules and fluorinated
counterparts revealed the importance of placing fluorine at the optimal position
to achieve favorable interactions with protein side chains.
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