1.
Bioorg Med Chem Lett
; 22(17): 5545-9, 2012 Sep 01.
Artigo
em Inglês
| MEDLINE
| ID: mdl-22850208
RESUMO
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.
Assuntos
Amidas/química , Amidas/farmacologia , Diabetes Mellitus Tipo 2/enzimologia , Dipeptidil Peptidase 4/metabolismo , Inibidores da Dipeptidil Peptidase IV/química , Inibidores da Dipeptidil Peptidase IV/farmacologia , Amidas/síntese química , Animais , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/síntese química , Cães , Teste de Tolerância a Glucose , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Modelos Moleculares , Piperazinas/síntese química , Piperazinas/química , Piperazinas/farmacologia , Ratos , Ratos Sprague-Dawley
2.
Bioorg Med Chem Lett
; 21(12): 3809-12, 2011 Jun 15.
Artigo
em Inglês
| MEDLINE
| ID: mdl-21570283
RESUMO
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.