Xie_2012_Eur.J.Med.Chem_52_205

Reference

Title : Novel pyrrolopyrimidine analogues as potent dipeptidyl peptidase IV inhibitors based on pharmacokinetic property-driven optimization - Xie_2012_Eur.J.Med.Chem_52_205
Author(s) : Xie H , Zeng L , Zeng S , Lu X , Zhang G , Zhao X , Cheng N , Tu Z , Li Z , Xu H , Yang L , Zhang X , Huang M , Zhao J , Hu W
Ref : Eur Journal of Medicinal Chemistry , 52 :205 , 2012
Abstract : We previously reported a highly potent DPP-IV inhibitor 6 with low in vivo efficacy. While trying to maintain consistent in vitro and in vivo biological activity, we initiated a pharmacokinetic property-driven optimization to improve the metabolic stability and permeability of inhibitor 6. A simple scaffold replacement of thienopyrimidine with pyrrolopyrimidine (21a) led to significantly improved metabolic stability (4% vs. 65% remaining). Further modification of the pyrrolopyrimidine scaffold to produce compound 21j resulted in much better oral bioavailability than 6. Importantly, compound 21j exhibits greater in vivo efficacy than does 6 and Alogliptin and is worthy of further development.
ESTHER : Xie_2012_Eur.J.Med.Chem_52_205
PubMedSearch : Xie_2012_Eur.J.Med.Chem_52_205
PubMedID: 22475866

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Citations formats

Xie H, Zeng L, Zeng S, Lu X, Zhang G, Zhao X, Cheng N, Tu Z, Li Z, Xu H, Yang L, Zhang X, Huang M, Zhao J, Hu W (2012)
Novel pyrrolopyrimidine analogues as potent dipeptidyl peptidase IV inhibitors based on pharmacokinetic property-driven optimization
Eur Journal of Medicinal Chemistry 52 :205

Xie H, Zeng L, Zeng S, Lu X, Zhang G, Zhao X, Cheng N, Tu Z, Li Z, Xu H, Yang L, Zhang X, Huang M, Zhao J, Hu W (2012)
Eur Journal of Medicinal Chemistry 52 :205