Paper Report for: Pei_2006_J.Med.Chem_49_6439 Reference
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
Pei Z , Li X , von Geldern TW , Madar DJ , Longenecker K , Yong H , Lubben TH , Stewart KD , Zinker BA and Trevillyan JM <12 more author(s)>
Pei Z , Li X , von Geldern TW , Madar DJ , Longenecker K , Yong H , Lubben TH , Stewart KD , Zinker BA , Backes BJ , Judd AS , Mulhern M , Ballaron SJ , Stashko MA , Mika AK , Beno DW , Reinhart GA , Fryer RM , Preusser LC , Kempf-Grote AJ , Sham HL , Trevillyan JM (- 12)
Ref: Journal of Medicinal Chemistry,
49 :6439, 2006 :
PubMed Abstract PubMedSearch: Pei 2006 J.Med.Chem 49 6439 PubMedID: 17064063 Gene_locus related to this paper: human-DPP4 Inhibitor(s) related to this paper: ABT-341 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.
        
Related information
Structure in RCSB-PDB | 2I78
Structure in ESTHER | 2I78
Citations formats
Pei Z, Li X, von Geldern TW, Madar DJ, Longenecker K, Yong H, Lubben TH, Stewart KD, Zinker BA, Backes BJ, Judd AS, Mulhern M, Ballaron SJ, Stashko MA, Mika AK, Beno DW, Reinhart GA, Fryer RM, Preusser LC, Kempf-Grote AJ, Sham HL, Trevillyan JM (2006) 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 diabetesJournal of Medicinal Chemistry 49 : 6439-42 Pei Z, Li X, von Geldern TW, Madar DJ, Longenecker K, Yong H, Lubben TH, Stewart KD, Zinker BA, Backes BJ, Judd AS, Mulhern M, Ballaron SJ, Stashko MA, Mika AK, Beno DW, Reinhart GA, Fryer RM, Preusser LC, Kempf-Grote AJ, Sham HL, Trevillyan JM (2006) Journal of Medicinal Chemistry 49 : 6439-42