4-Aryleyelohexylaianine analogs as potent, selective, and orally active inhibitors of dipeptidyl peptidase IV

Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.
Bioorganic & Medicinal Chemistry Letters (Impact Factor: 2.42). 12/2007; 17(21):5806-11. DOI: 10.1016/j.bmcl.2007.08.049
Source: PubMed


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 IC50 = 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. (c) 2007 Elsevier Ltd. All rights reserved.

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