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Literature DB >> 17064063

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.

Zhonghua Pei¹, Xiaofeng Li, Thomas W von Geldern, David J Madar, Kenton Longenecker, Hong Yong, Thomas H Lubben, Kent D Stewart, Bradley A Zinker, Bradley J Backes, Andrew S Judd, Mathew Mulhern, Stephen J Ballaron, Michael A Stashko, Amanda K Mika, David W A Beno, Glenn A Reinhart, Ryan M Fryer, Lee C Preusser, Anita J Kempf-Grote, Hing L Sham, James M Trevillyan.

Abstract

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 agent for the treatment of type 2 diabetes.

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Year: 2006 PMID： 17064063 DOI： 10.1021/jm060955d

Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446

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Cited

5 in total

1. Hit clustering can improve virtual fragment screening: CDK2 and PARP1 case studies.

Authors: Alexey A Zeifman; Victor S Stroylov; Fedor N Novikov; Oleg V Stroganov; Alexandra L Zakharenko; Svetlana N Khodyreva; Olga I Lavrik; Ghermes G Chilov
Journal: J Mol Model Date: 2011-11-09 Impact factor: 1.810

2. Synthesis and evaluation of novologues as C-terminal Hsp90 inhibitors with cytoprotective activity against sensory neuron glucotoxicity.

Authors: Bhaskar Reddy Kusuma; Liang Zhang; Teather Sundstrom; Laura B Peterson; Rick T Dobrowsky; Brian S J Blagg
Journal: J Med Chem Date: 2012-06-15 Impact factor: 7.446

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.

1. Hit clustering can improve virtual fragment screening: CDK2 and PARP1 case studies.

2. Synthesis and evaluation of novologues as C-terminal Hsp90 inhibitors with cytoprotective activity against sensory neuron glucotoxicity.

3. Rapid Access to Multisubstituted Acrylamides from Cyclic Ketones via Palladium/Norbornene Cooperative Catalysis.

4. Comprehensive analysis of the Co-structures of dipeptidyl peptidase IV and its inhibitor.

5. Pot economy and one-pot synthesis.