Namoto, Kenji, Sirockin, Finton, Ostermann, Nils, Gessier, Francois, Flohr, Stefanie, Sedrani, Richard, Gerhartz, Bernd, Trappe, Joerg, Hassiepen, Ulrich, Duttaroy, Alokesh, Ferreira, Suzie, Sutton, Jon M., Clark, David E., Fenton, Gary, Beswick, Mandy and Baeschlin, Daniel (2014) Discovery of C-(1-aryl-cyclohexyl)-methylamines as selective, orally available inhibitors of dipeptidyl peptidase IV. Bioorganic & Medicinal Chemistry Letters, 24 (3). pp. 731-736.

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 DPPIV 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 phamacokinetic profile in the rat.

Item Type:	Article
Keywords:	protease inhibition, dipeptidyl peptidase IV, structure-based drug design, selectivity, pharmacokinetics
Date Deposited:	04 May 2016 23:45
Last Modified:	04 May 2016 23:45
URI:	https://oak.novartis.com/id/eprint/10024