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PDBsum entry 2j9m
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References listed in PDB file
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Key reference
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Title
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Macrocyclic aminopyrimidines as multitarget cdk and vegf-R inhibitors with potent antiproliferative activities.
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Authors
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U.Lücking,
G.Siemeister,
M.Schäfer,
H.Briem,
M.Krüger,
P.Lienau,
R.Jautelat.
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Ref.
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Chemmedchem, 2007,
2,
63-77.
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PubMed id
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Abstract
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X-ray structures from CDK2-aminopyrimidine inhibitor complexes led to the idea
to stabilize the active conformation of aminopyrimidine inhibitors by
incorporating the recognition site into a macrocyclic framework. A modular
synthesis approach that relies on a new late-stage macrocyclization protocol
that enables fast and efficient synthesis of macrocyclic aminopyrimidines was
developed. A set of structurally diverse derivatives was prepared. Macrocyclic
aminopyrimidines were shown to be multitarget inhibitors of CDK1/2 and
VEGF-RTKs. In addition, potent antiproliferative activities toward various human
tumor cells and a human tumor xenograft model were demonstrated.
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