Optimization of 1,4-diazepan-2-one containing dipeptidyl peptidase IV inhibitors for the treatment of type 2 diabetes.

@article{Liang2007OptimizationO1,
  title={Optimization of 1,4-diazepan-2-one containing dipeptidyl peptidase IV inhibitors for the treatment of type 2 diabetes.},
  author={Gui Bai Liang and Xiaoxia Qian and Dennis Feng and Tesfaye Biftu and George J. Eiermann and Huaibing He and Barbara Leiting and Kathy Lyons and Aleksandr Petrov and Ranabir Sinha-Roy and Bei B. Zhang and Joseph K. Wu and Xiaoping Zhang and Nancy Ann Thornberry and Ann E. Weber},
  journal={Bioorganic \& medicinal chemistry letters},
  year={2007},
  volume={17 7},
  pages={
          1903-7
        }
}
  • G. Liang, X. Qian, A. Weber
  • Published 1 April 2007
  • Chemistry, Biology
  • Bioorganic & medicinal chemistry letters
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(2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine: a potent, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes.
TLDR
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Assessment of selectivity of potential clinical candidates may be important to an optimal safety profile for this new class of antihyperglycemic agents, according to the results of toxicity and tolerability studies.
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Kinetic investigation of human dipeptidyl peptidase II (DPPII)-mediated hydrolysis of dipeptide derivatives and its identification as quiescent cell proline dipeptidase (QPP)/dipeptidyl peptidase 7 (DPP7).
TLDR
P pH profiles of both kcat and kcat/K(m) clearly demonstrated that DPPII/QPP possesses an acidic and not a neutral optimum as was reported for QPP, explaining many discrepancies in the literature.
Dipeptidyl peptidase IV inhibition potentiates the insulinotropic effect of glucagon-like peptide 1 in the anesthetized pig.
TLDR
By reducing GLP-1 degradation, DPP IV inhibition potentiates the insulinotropic effect of GLP1 and may, therefore, be a viable approach to the management of diabetes.
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