Abstract
A convergent synthesis of alpha-ketoamide inhibitors of Pin1 is described. An alpha-hydroxyorthothioester derivative of Ser was reacted directly with an amine synthon. The reaction was catalyzed by HgO and HgCl(2) to form alpha-hydroxyamide. Thus, hydrolysis and coupling were combined in one step with 80% yield. Two diastereomers of a phospho-Ser-Pro alpha-ketoamide analogue were synthesized. The IC(50) values of 100 and 200 microM were surprisingly weak for Pin1 peptidyl prolyl isomerase.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Amides / chemical synthesis*
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Amides / chemistry
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Amides / pharmacology
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Inhibitory Concentration 50
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Ketones / chemical synthesis*
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Ketones / chemistry
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Ketones / pharmacology*
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Molecular Structure
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NIMA-Interacting Peptidylprolyl Isomerase
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Peptidylprolyl Isomerase / antagonists & inhibitors*
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Stereoisomerism
Substances
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Amides
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Enzyme Inhibitors
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Ketones
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NIMA-Interacting Peptidylprolyl Isomerase
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Peptidylprolyl Isomerase