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.
Subject(s)
Dipeptidyl-Peptidase IV Inhibitors/chemical synthesis , Piperazines/chemical synthesis , Administration, Oral , Animals , Diabetes Mellitus, Type 2/drug therapy , Dipeptidyl-Peptidase IV Inhibitors/chemistry , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Disease Models, Animal , Humans , Inhibitory Concentration 50 , Piperazines/chemistry , Piperazines/pharmacology , Rats , Structure-Activity RelationshipABSTRACT
Four compounds of a coumarin, a steroid and two flavonoids were isolated from the herba of Artemisia apiacea by open column chromatography. Their structures were elucidated as artemicapin C, apigenin, daucosterol and cacticin by chemical and spectroscopic analysis. This is the first report of the isolation of these compounds from this plant.
