1.
Bioorg Med Chem
; 19(23): 7221-7, 2011 Dec 01.
Article
in English
| MEDLINE
| ID: mdl-22019046
ABSTRACT
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.
Subject(s)
Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Pyrimidines/pharmacology , Animals , Dipeptidyl Peptidase 4/metabolism , Dipeptidyl-Peptidase IV Inhibitors/chemistry , Dipeptidyl-Peptidase IV Inhibitors/pharmacokinetics , Dogs , Humans , Male , Pyrimidines/administration & dosage , Pyrimidines/chemistry , Pyrimidines/pharmacokinetics , Pyrimidines/therapeutic use , Rats , Rats, Sprague-Dawley , Rats, Wistar , Structure-Activity Relationship
2.
Org Med Chem Lett
; 1(1): 7, 2011 Sep 12.
Article
in English
| MEDLINE
| ID: mdl-22373386
ABSTRACT
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.