Discovery of ((4R,5S)-5-amino-4-(2,4,5- trifluorophenyl)cyclohex-1-enyl)-(3- (trifluoromethyl)-5,6-dihydro- [1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methanone (ABT-341), a highly potent, selective, orally efficacious, and safe dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes.

@article{Pei2006DiscoveryO,
  title={Discovery of ((4R,5S)-5-amino-4-(2,4,5- trifluorophenyl)cyclohex-1-enyl)-(3- (trifluoromethyl)-5,6-dihydro- [1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methanone (ABT-341), a highly potent, selective, orally efficacious, and safe dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes.},
  author={Zhonghua Pei and Xiao-Feng Li and Thomas W. von Geldern and David J Madar and Kenton L Longenecker and Hong Chan Yong and Thomas H Lubben and Kent D. Stewart and Bradley A. Zinker and Bradley J. Backes and Andrew S Judd and Mathew M Mulhern and Stephen J Ballaron and Michael A. Stashko and Amanda K Mika and David W A Beno and Glenn A. Reinhart and Ryan M. Fryer and Lee C Preusser and Anita J Kempf-Grote and Hing Leung Sham and James M Trevillyan},
  journal={Journal of medicinal chemistry},
  year={2006},
  volume={49 22},
  pages={6439-42}
}
Dipeptidyl peptidase IV (DPP4) deactivates glucose-regulating hormones such as GLP-1 and GIP, thus, DPP4 inhibition has become a useful therapy for type 2 diabetes. Optimization of the high-throughput screening lead 6 led to the discovery of 25 (ABT-341), a highly potent, selective, and orally bioavailable DPP4 inhibitor. When dosed orally, 25 dose-dependently reduced glucose excursion in ZDF rats. Amide 25 is safe in a battery of in vitro and in vivo tests and may represent a new therapeutic… CONTINUE READING