Download MendeleyDiscovery of C-(1-aryl-cyclohexyl)-methylamines as selective, orally available inhibitors of dipeptidyl peptidase IV.
Namoto, K., Sirockin, F., Ostermann, N., Gessier, F., Flohr, S., Sedrani, R., Gerhartz, B., Trappe, J., Hassiepen, U., Duttaroy, A., Ferreira, S., Sutton, J.M., Clark, D.E., Fenton, G., Beswick, M., Baeschlin, D.K.(2014) Bioorg Med Chem Lett 24: 731-736
- PubMed: 24439847
- DOI: https://doi.org/10.1016/j.bmcl.2013.12.118
- Primary Citation of Related Structures:
4N8D, 4N8E - PubMed Abstract:
The successful launches of dipeptidyl peptidase IV (DPP IV) inhibitors as oral anti-diabetics warrant and spur the further quest for additional chemical entities in this promising class of therapeutics. Numerous pharmaceutical companies have pursued their proprietary candidates towards the clinic, resulting in a large body of published chemical structures associated with DPP IV. Herein, we report the discovery of a novel chemotype for DPP IV inhibition based on the C-(1-aryl-cyclohexyl)-methylamine scaffold and its optimization to compounds which selectively inhibit DPP IV at low-nM potency and exhibit an excellent oral pharmacokinetic profile in the rat.
Organizational Affiliation:
Novartis Institutes for BioMedical Research, Novartis Campus, CH-4002 Basel, Switzerland. Electronic address: kenji.namoto@novartis.com.
