Abstract
A series of β-amino amide containing substituted piperazine-2-one derivatives was synthesized and evaluated as inhibitors of dipeptidyl pepdidase-4 (DPP-4) for the treatment of type 2 diabetes. As results of intensive SAR study of the series, (R)-4-[(R)-3-amino-4-(2,4,5-trifluorophenyl)-butanoyl]-3-(t-butoxymethyl)-piperazin-2-one (DA-1229) displayed potent DPP-4 inhibition pattern in several animal models, was selected for clinical development.
Copyright © 2011 Elsevier Ltd. All rights reserved.
MeSH terms
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Administration, Oral
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Animals
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Diabetes Mellitus, Type 2 / drug therapy
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Dipeptidyl-Peptidase IV Inhibitors / chemical synthesis*
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Dipeptidyl-Peptidase IV Inhibitors / chemistry
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Dipeptidyl-Peptidase IV Inhibitors / pharmacology
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Disease Models, Animal
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Humans
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Inhibitory Concentration 50
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Piperazines / chemical synthesis*
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Piperazines / chemistry
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Piperazines / pharmacology
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Rats
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Structure-Activity Relationship
Substances
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4-(3-amino-4-(2,4,5-trifluorophenyl)butanoyl)-3-(tert-butoxymethyl)piperazin-2-one
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Dipeptidyl-Peptidase IV Inhibitors
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Piperazines