| Title : 4-arylcyclohexylalanine analogs as potent, selective, and orally active inhibitors of dipeptidyl peptidase IV - Kaelin_2007_Bioorg.Med.Chem.Lett_17_5806 |
| Author(s) : Kaelin DE , Smenton AL , Eiermann GJ , He H , Leiting B , Lyons KA , Patel RA , Patel SB , Petrov A , Scapin G , Wu JK , Thornberry NA , Weber AE , Duffy JL |
| Ref : Bioorganic & Medicinal Chemistry Lett , 17 :5806 , 2007 |
|
Abstract :
A novel series of 4-arylcyclohexylalanine DPP-4 inhibitors was synthesized and tested for inhibitory activity as well as selectivity over the related proline-specific enzymes DPP-8 and DPP-9. Optimization of this series led to 28 (DPP-4 IC(50)=4.8 nM), which showed an excellent pharmacokinetic profile across several preclinical species. Evaluation of 28 in an oral glucose tolerance test demonstrated that this compound effectively reduced glucose excursion in lean mice. |
| PubMedSearch : Kaelin_2007_Bioorg.Med.Chem.Lett_17_5806 |
| PubMedID: 17851076 |
| Gene_locus related to this paper: human-DPP4 |
| Inhibitor | 4-aryl-cyclohexylalanine-inhibitor-1 4-aryl-cyclohexylalanine-inhibitor-2 |
| Gene_locus | human-DPP4 |
| Structure | 2QTB 2QT9 |
Kaelin DE, Smenton AL, Eiermann GJ, He H, Leiting B, Lyons KA, Patel RA, Patel SB, Petrov A, Scapin G, Wu JK, Thornberry NA, Weber AE, Duffy JL (2007)
4-arylcyclohexylalanine analogs as potent, selective, and orally active inhibitors of dipeptidyl peptidase IV
Bioorganic & Medicinal Chemistry Lett
17 :5806
Kaelin DE, Smenton AL, Eiermann GJ, He H, Leiting B, Lyons KA, Patel RA, Patel SB, Petrov A, Scapin G, Wu JK, Thornberry NA, Weber AE, Duffy JL (2007)
Bioorganic & Medicinal Chemistry Lett
17 :5806