Structure Report for: 2I78

Pei, Z., Li, X., vonGeldern, T.W., Madar, D.J., L Longenecker, K., Yong, H., Lubben, T.H., Stewart, K.D., Zinker, B.A., Backes, B.J., Judd, A.S., Mulhern, M., Ballaron, S.J., Stashko, M.A., Mika, A.K., Beno, D.W.A., Reinhart, G.A., Fryer, R.M., Preusser, L.C., Kempf-Grote, A.J., Sham, H.L., Trevillyan, J.M. Discovery of Cyclohexene-constrained Phenethylamine ABT-341, a Highly Potent, Selective, Orally Bioavailable, Safe and Potential Next-generation Dipeptidyl Peptidase IV Inhibitor for the Treatment of Type 2 Diabetes To be Published

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


ESTHER: Pei_2006_J.Med.Chem_49_6439
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.