4-arylcyclohexylalanine analogs as potent, selective, and orally active inhibitors of dipeptidyl peptidase IV.
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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
4-arylcyclohexylalanine analogs as potent, selective, and orally active inhibitors of dipeptidyl peptidase IV.
Bioorg Med Chem Lett. 2007 Nov 1;17(21):5806-11. Epub 2007 Aug 26.
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- 17851076 [ View in PubMed]
- 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.
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