Abstract
We have systematically explored the structure-activity relationship (SAR) for a series of compounds 2 as inhibitors of tripeptidyl-peptidase II (TPP II), a serine protease responsible for the degradation of cholecystokinin-8 (CCK-8). This SAR evaluation of the core structure 2 suggest a fairly restrictive pharmacophore for such related structures, but has yielded a limited set of compounds (2b, 2c, 2d, 2s, and 2t) with potent TPP II inhibitory activity (IC(50) 4-11 nM).
MeSH terms
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Aminopeptidases
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Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
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Imidazoles / chemistry
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Imidazoles / pharmacology
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Indoles / chemical synthesis*
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Indoles / chemistry
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Indoles / pharmacology*
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Kinetics
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Models, Molecular
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Molecular Structure
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Protease Inhibitors / chemical synthesis*
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Protease Inhibitors / chemistry
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Protease Inhibitors / pharmacology*
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Serine Endopeptidases / metabolism*
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Structure-Activity Relationship
Substances
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Imidazoles
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Indoles
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Protease Inhibitors
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Aminopeptidases
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Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
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tripeptidyl-peptidase 2
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Serine Endopeptidases