Abstract
A novel family of peptidomimetics incorporating fluoroalkyl groups, mainly a trifluoromethyl, in alpha-position to a zinc(II)-binding thiol function, was synthesized in solution as well as in solid-phase. These compounds showed inhibitory potency in the nanomolar range against both angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP), whereas no inhibition of endothelin-converting enzyme-1 (ECE-1) was observed. The trifluoromethyl-derivatives were more potent than the parent unfluorinated analogues in the case of ACE, and less potent in the case of NEP.
MeSH terms
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Angiotensin-Converting Enzyme Inhibitors / chemical synthesis*
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Angiotensin-Converting Enzyme Inhibitors / chemistry
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Angiotensin-Converting Enzyme Inhibitors / pharmacology
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Fluorine / chemistry*
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Humans
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Neprilysin / antagonists & inhibitors*
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Neprilysin / metabolism
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Peptides / chemistry
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Peptidyl-Dipeptidase A / chemistry*
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Peptidyl-Dipeptidase A / metabolism
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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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Sulfhydryl Compounds / chemical synthesis*
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Sulfhydryl Compounds / chemistry
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Sulfhydryl Compounds / pharmacology
Substances
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Angiotensin-Converting Enzyme Inhibitors
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Peptides
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Protease Inhibitors
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Sulfhydryl Compounds
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Fluorine
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Peptidyl-Dipeptidase A
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Neprilysin