| 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, OrallyEfficacious, and Safe Dipeptidyl Peptidase IVInhibitor for the Treatment of Type 2 Diabetes
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| Abstract
| - Dipeptidyl peptidase IV (DPP4) deactivates glucose-regulating hormones such as GLP-1 and GIP, thus, DPP4 inhibitionhas become a useful therapy for type 2 diabetes. Optimization of thehigh-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 excursionin ZDF rats. Amide 25 is safe in a battery of in vitro and in vivo testsand may represent a new therapeutic agent for the treatment of type 2diabetes.
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