Bioorganic and Medicinal Chemistry Letters p. 731 - 736 (2014)
Update date:2022-09-26
Topics:
Namoto, Kenji
Sirockin, Finton
Ostermann, Nils
Gessier, Francois
Flohr, Stefanie
Sedrani, Richard
Gerhartz, Bernd
Trappe, J?rg
Hassiepen, Ulrich
Duttaroy, Alokesh
Ferreira, Suzie
Sutton, Jon M.
Clark, David E.
Fenton, Garry
Beswick, Mandy
Baeschlin, Daniel K.
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. 2014 Elsevier Ltd. All rights reserved.
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