| Title : 4-aminophenylalanine and 4-aminocyclohexylalanine derivatives as potent, selective, and orally bioavailable inhibitors of dipeptidyl peptidase IV - Duffy_2007_Bioorg.Med.Chem.Lett_17_2879 |
| Author(s) : Duffy JL , Kirk BA , Wang L , Eiermann GJ , He H , Leiting B , Lyons KA , Patel RA , Patel SB , Petrov A , Scapin G , Wu JK , Thornberry NA , Weber AE |
| Ref : Bioorganic & Medicinal Chemistry Lett , 17 :2879 , 2007 |
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Abstract :
A novel series of 4-aminophenylalanine and 4-aminocyclohexylalanine derivatives were designed and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-4). The phenylalanine series afforded compounds such as 10 that were potent and selective (DPP-4, IC(50)=28nM), but exhibited limited oral bioavailability. The corresponding cyclohexylalanine derivatives such as 25 afforded improved PK exposure and efficacy in a murine OGTT experiment. The X-ray crystal structure of 25 bound to the DPP-4 active site is presented. |
| PubMedSearch : Duffy_2007_Bioorg.Med.Chem.Lett_17_2879 |
| PubMedID: 17350841 |
| Gene_locus related to this paper: human-DPP4 |
| Inhibitor | 4-aminocyclohexylalanine-derivative-25 |
| Gene_locus | 4-aminocyclohexylalanine-derivative-25 human-DPP4 |
| Structure | 4-aminocyclohexylalanine-derivative-25 human-DPP4 2OPH |
Duffy JL, Kirk BA, Wang L, Eiermann GJ, He H, Leiting B, Lyons KA, Patel RA, Patel SB, Petrov A, Scapin G, Wu JK, Thornberry NA, Weber AE (2007)
4-aminophenylalanine and 4-aminocyclohexylalanine derivatives as potent, selective, and orally bioavailable inhibitors of dipeptidyl peptidase IV
Bioorganic & Medicinal Chemistry Lett
17 :2879
Duffy JL, Kirk BA, Wang L, Eiermann GJ, He H, Leiting B, Lyons KA, Patel RA, Patel SB, Petrov A, Scapin G, Wu JK, Thornberry NA, Weber AE (2007)
Bioorganic & Medicinal Chemistry Lett
17 :2879