1.
Bioorg Med Chem
; 19(23): 7221-7, 2011 Dec 01.
Artigo
em Inglês
| MEDLINE
| ID: mdl-22019046
RESUMO
In the course of our program for discovery of novel DPP-IV inhibitors, a series of pyrazolo[1,5-a]pyrimidines were found to be novel DPP-IV inhibitors. We identified N-[2-({2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl}amino)-2-methylpropyl]-2-methylpyrazolo[1,5-a]pyrimidine-6-carboxamide hydrochloride (4a) and described its pharmacological profiles.
Assuntos
Inibidores da Dipeptidil Peptidase IV/farmacologia , Pirimidinas/farmacologia , Animais , Dipeptidil Peptidase 4/metabolismo , Inibidores da Dipeptidil Peptidase IV/química , Inibidores da Dipeptidil Peptidase IV/farmacocinética , Cães , Humanos , Masculino , Pirimidinas/administração & dosagem , Pirimidinas/química , Pirimidinas/farmacocinética , Pirimidinas/uso terapêutico , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Relação Estrutura-Atividade
2.
Org Med Chem Lett
; 1(1): 7, 2011 Sep 12.
Artigo
em Inglês
| MEDLINE
| ID: mdl-22373386
RESUMO
Focused structure-activity relationships of isoindoline class DPP-IV inhibitors have led to the discovery of 4b as a highly selective, potent inhibitor of DPP-IV. In vivo studies in Wistar/ST rats showed that 4b was converted into the strongly active metabolite 4l in high yield, resulting in good in vivo efficacy for antihyperglycemic activity.