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PDBsum entry 2g9x
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Transferase/cell cycle
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PDB id
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2g9x
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Contents |
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299 a.a.
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262 a.a.
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275 a.a.
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References listed in PDB file
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Key reference
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Title
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Searching for cyclin-Dependent kinase inhibitors using a new variant of the cope elimination.
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Authors
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R.J.Griffin,
A.Henderson,
N.J.Curtin,
A.Echalier,
J.A.Endicott,
I.R.Hardcastle,
D.R.Newell,
M.E.Noble,
L.Z.Wang,
B.T.Golding.
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Ref.
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J Am Chem Soc, 2006,
128,
6012-6013.
[DOI no: ]
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PubMed id
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Abstract
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beta-Piperidinoethylsulfides are oxidized by m-chloroperbenzoic acid to
intermediates containing both N-oxide and sulfone functions. These undergo a
Cope-type elimination to a vinylsulfone that can be captured by amines to afford
beta-aminoethylsulfones. When a beta-aminoethylsulfone group is linked to the
4-position of a phenyl group attached at N-2 of O6-cyclohexylmethylguanine, the
resulting derivatives are inhibitors of the cyclin-dependent kinase CDK2. One of
the most potent inhibitors (IC50 = 45 nM) contained a N-3-hydroxypropyl group on
the aminoethylsulfonyl substituent. The crystal structure of this inhibitor
bound to CDK2/cyclin A was determined and shows an unusual network of hydrogen
bonds. The synthetic methodology developed can be utilized in multiple-parallel
format and has numerous potential applications in medicinal chemistry.
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