1.
Eur J Med Chem
; 46(1): 71-6, 2011 Jan.
Artículo
en Inglés
| MEDLINE
| ID: mdl-21106276
RESUMEN
New dipeptidyl peptidase IV inhibitors were designed based on Alogliptin using a scaffold-hopping strategy. All of the compounds constructed on a thienopyrimidine scaffold demonstrated good inhibition and selectivity for DPP-IV. Compound 10d exhibited subnanomolar (IC(50)=0.33nM) DPP-IV inhibitory activity, good in vivo efficacy and an acceptable pharmacokinetic profile. A pharmacokinetic-driven optimization of 10d may lead to a new class of clinical candidate DPP-IV inhibitors.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Dipeptidil Peptidasa 4/metabolismo , Inhibidores de la Dipeptidil-Peptidasa IV/química , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Pirimidinas/química , Pirimidinas/farmacología , Animales , Glucemia/metabolismo , Inhibidores de la Dipeptidil-Peptidasa IV/farmacocinética , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Perros , Descubrimiento de Drogas , Células HEK293 , Humanos , Masculino , Piperidinas/química , Pirimidinas/farmacocinética , Pirimidinas/uso terapéutico , Ratas , Uracilo/análogos & derivados , Uracilo/química
2.
Bioorg Med Chem Lett
; 17(8): 2123-5, 2007 Apr 15.
Artículo
en Inglés
| MEDLINE
| ID: mdl-17317172
RESUMEN
A new class of inhibitors of acetylcholinesterase (methyl 2-(2-(4-formylphenoxy)acetamido)-2-substituted acetate derivatives) is described. Compounds 4b and 4i were found to be more potent than galanthamine in inhibiting acetylcholinesterase.
