| Title : The discovery of novel 5,6,5- and 5,5,6-tricyclic pyrrolidines as potent and selective DPP-4 inhibitors - Cox_2016_Bioorg.Med.Chem.Lett_26_2622 |
| Author(s) : Cox JM , Chu HD , Kuethe JT , Gao YD , Scapin G , Eiermann G , He H , Li X , Lyons KA , Metzger J , Petrov A , Wu JK , Xu S , Sinha-Roy R , Weber AE , Biftu T |
| Ref : Bioorganic & Medicinal Chemistry Lett , 26 :2622 , 2016 |
|
Abstract :
Novel potent and selective 5,6,5- and 5,5,6-tricyclic pyrrolidine dipeptidyl peptidase IV (DPP-4) inhibitors were identified. Structure-activity relationship (SAR) efforts focused on improving the intrinsic DPP-4 inhibition potency, increasing protease selectivity, and demonstrating clean ion channel and cytochrome P450 profiles while trying to achieve a pharmacokinetic profile suitable for once weekly dosing in humans. |
| PubMedSearch : Cox_2016_Bioorg.Med.Chem.Lett_26_2622 |
| PubMedID: 27106708 |
| Gene_locus related to this paper: human-DPP4 |
| Inhibitor | 5ISM-6DG |
| Gene_locus | human-DPP4 |
| Structure | 5ISM |
Cox JM, Chu HD, Kuethe JT, Gao YD, Scapin G, Eiermann G, He H, Li X, Lyons KA, Metzger J, Petrov A, Wu JK, Xu S, Sinha-Roy R, Weber AE, Biftu T (2016)
The discovery of novel 5,6,5- and 5,5,6-tricyclic pyrrolidines as potent and selective DPP-4 inhibitors
Bioorganic & Medicinal Chemistry Lett
26 :2622
Cox JM, Chu HD, Kuethe JT, Gao YD, Scapin G, Eiermann G, He H, Li X, Lyons KA, Metzger J, Petrov A, Wu JK, Xu S, Sinha-Roy R, Weber AE, Biftu T (2016)
Bioorganic & Medicinal Chemistry Lett
26 :2622