1.
Bioorg Med Chem Lett
; 22(17): 5545-9, 2012 Sep 01.
Article
in English
| MEDLINE
| ID: mdl-22850208
ABSTRACT
Inhibitors of dipeptidyl peptidase-4 (DPP4) have been shown to be effective treatments for type 2 diabetes. Several series of ß-amino amide containing piperazine derivatives have been prepared and evaluated as a inhibitor of DPP4. Finally compound 5m was selected for further evaluation.
Subject(s)
Amides/chemistry , Amides/pharmacology , Diabetes Mellitus, Type 2/enzymology , Dipeptidyl Peptidase 4/metabolism , Dipeptidyl-Peptidase IV Inhibitors/chemistry , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Amides/chemical synthesis , Animals , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/drug therapy , Dipeptidyl-Peptidase IV Inhibitors/chemical synthesis , Dogs , Glucose Tolerance Test , Humans , Mice , Mice, Inbred C57BL , Models, Molecular , Piperazines/chemical synthesis , Piperazines/chemistry , Piperazines/pharmacology , Rats , Rats, Sprague-Dawley
2.
Bioorg Med Chem Lett
; 21(12): 3809-12, 2011 Jun 15.
Article
in English
| MEDLINE
| ID: mdl-21570283
ABSTRACT
A series of ß-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.
