Synthesis and kinase inhibitory activity of 3'-(S)-epi-K-252a

The 3'-epi diastereomer of K-252a was synthesized with the goal of evaluating the stereochemical requirements of the 3'-sugar alcohol on kinase inhibitory activity. Inverting the 3'-alcohol resulted in a 20 nM inhibitor of VEGFR2 and a 1 nM inhibitor of TrkA tyrosine kinase.

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Bibliographic Details
Published inBioorganic & medicinal chemistry letters Vol. 12; no. 20; pp. 2829 - 2831
Main Authors GINGRICH, Diane E, HUDKINS, Robert L
Format Journal Article
LanguageEnglish
Published Oxford Elsevier 21.10.2002
Subjects
Alcohols - chemical synthesis
Alcohols - chemistry
Alcohols - pharmacology
Antineoplastic agents
Biological and medical sciences
Carbazoles - chemical synthesis
Carbazoles - pharmacology
Chromatography, High Pressure Liquid
Enzyme Inhibitors - chemical synthesis
Enzyme Inhibitors - pharmacology
General aspects
Indole Alkaloids
Magnetic Resonance Spectroscopy
Medical sciences
Models, Molecular
Pharmacology. Drug treatments
Phosphotransferases - antagonists & inhibitors
Receptor, trkA - antagonists & inhibitors
Stereoisomerism
Vascular Endothelial Growth Factor Receptor-2 - antagonists & inhibitors
Protein kinase C
Enzyme
Transferases
Epimer
Lactam
Enzyme inhibitor
Polycyclic compound
In vitro
Biological activity
Myosin-light-chain kinase
Alkaloid
Growth factor receptor
Vascular endothelium growth factor
Protein kinase
S configuration
Aromatic compound
Inhibition
Chemical synthesis
Oxygen nitrogen heterocycle
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Summary:The 3'-epi diastereomer of K-252a was synthesized with the goal of evaluating the stereochemical requirements of the 3'-sugar alcohol on kinase inhibitory activity. Inverting the 3'-alcohol resulted in a 20 nM inhibitor of VEGFR2 and a 1 nM inhibitor of TrkA tyrosine kinase.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:0960-894X
1464-3405
DOI:10.1016/S0960-894X(02)00638-8