Abstract
Racemic 5-substituted 7-aminobenzocyclohepten-6-one were synthesized and evaluated for their ability to inhibit metalloaminopeptidase activities. Unexpectedly, 5-thio substituted compounds showed enhanced inhibition potency with K(i) values in the nanomolar range against the 'one zinc' aminopeptidases from the M1 family, while most of them were rather poor inhibitors of the 'two zincs' enzymes from the M17 family. This interesting selectivity profile may guide the design of new, specific inhibitors of target mammalian aminopeptidases with one active site zinc.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aminopeptidases / antagonists & inhibitors*
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Aminopeptidases / metabolism
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Animals
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Anisoles / chemical synthesis
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Anisoles / chemistry
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Anisoles / pharmacology*
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Cycloheptanes / chemical synthesis
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Cycloheptanes / chemistry
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Cycloheptanes / pharmacology*
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Dose-Response Relationship, Drug
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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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Kidney / enzymology
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Molecular Structure
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Stereoisomerism
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Structure-Activity Relationship
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Swine
Substances
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Anisoles
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Cycloheptanes
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Enzyme Inhibitors
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amino-benzosuberone
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Aminopeptidases