| 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_2006_J.Med.Chem_49_6439 |
| 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 |
| Ref : Journal of Medicinal Chemistry , 49 :6439 , 2006 |
|
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. |
| PubMedSearch : Pei_2006_J.Med.Chem_49_6439 |
| PubMedID: 17064063 |
| Gene_locus related to this paper: human-DPP4 |
| Inhibitor | ABT-341 |
| Gene_locus | human-DPP4 |
| Structure | 2I78 |
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 diabetes
Journal of Medicinal Chemistry
49 :6439
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