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PDBsum entry 2w17
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References listed in PDB file
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Key reference
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Title
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The discovery of azd5597, A potent imidazole pyrimidine amide cdk inhibitor suitable for intravenous dosing.
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Authors
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C.D.Jones,
D.M.Andrews,
A.J.Barker,
K.Blades,
P.Daunt,
S.East,
C.Geh,
M.A.Graham,
K.M.Johnson,
S.A.Loddick,
H.M.Mcfarland,
A.Mcgregor,
L.Moss,
D.A.Rudge,
P.B.Simpson,
M.L.Swain,
K.Y.Tam,
J.A.Tucker,
M.Walker.
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Ref.
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Bioorg Med Chem Lett, 2008,
18,
6369-6373.
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PubMed id
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Abstract
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The development of a novel series of imidazole pyrimidine amides as
cyclin-dependent kinase (CDK) inhibitors is described. Optimisation of
inhibitory potency against multiple CDK's (1, 2 and 9) resulted in imidazole
pyrimidine amides with potent in vitro anti-proliferative effects against a
range of cancer cell lines. Excellent physiochemical properties and large
margins against inhibition of CYP isoforms and the hERG ion channel were
achieved by modification of lipophilicity and amine basicity. A candidate with
disease model activity in human cancer cell line xenografts and with suitable
physiochemical and pharmacokinetic profiles for intravenous (i.v.) dosing was
selected for further development as AZD5597.
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