| Autor: |
D. Edmondson, Scott, Mastracchio, Anthony, J. Mathvink, Robert, He, Jiafang, Harper, Bart, Park, You-Jung, Beconi, Maria, Di Salvo, Jerry, J. Eiermann, George, He, Huaibing, Leiting, Barbara, F. Leone, Joseph, A. Levorse, Dorothy, Lyons, Kathryn, A. Patel, Reshma, B. Patel, Sangita, Petrov, Aleksandr, Scapin, Giovanna, Shang, Jackie, Sinha Roy, Ranabir, Smith, Aaron, K. Wu, Joseph, Xu, Shiyao, Zhu, Bing, A. Thornberry, Nancy, E. Weber, Ann |
| Zdroj: |
Journal of Medicinal Chemistry; June 2006, Vol. 49 Issue: 12 p3614-3627, 14p |
| Abstrakt: |
A series of β-substituted biarylphenylalanine amides were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-4) for the treatment of type 2 diabetes. Optimization of the metabolic profile of early analogues led to the discovery of (2S,3S)-3-amino-4-(3,3-difluoropyrrolidin-1-yl)-N,N-dimethyl-4-oxo-2-(4-[1,2,4]triazolo[1,5-a]pyridin-6-ylphenyl)butanamide (6), a potent, orally active DPP-4 inhibitor (IC50 = 6.3 nM) with excellent selectivity, oral bioavailability in preclinical species, and in vivo efficacy in animal models. Compound 6 was selected for further characterization as a potential new treatment for type 2 diabetes. |
| Databáze: |
Supplemental Index |
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