Bioorganic & Medicinal Chemistry Letters 2011-03-15

Synthesis and evaluation of [(1R)-1-amino-2-(2,5-difluorophenyl)ethyl]cyclohexanes and 4-[(1R)-1-amino-2-(2,5-difluorophenyl)ethyl]piperidines as DPP-4 inhibitors.

Ping Chen, Charles G Caldwell, Wallace Ashton, Joseph K Wu, Huaibing He, Kathryn A Lyons, Nancy A Thornberry, Ann E Weber

Index: Bioorg. Med. Chem. Lett. 21 , 1880-1886, (2011)

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Abstract

A series of 4-amino cyclohexanes and 4-substituted piperidines were prepared and evaluated for inhibition of DPP-4. Analog 20q displayed both good DPP-4 potency and selectivity against other proteases, while derivative 20k displayed long half life and modest oral bioavailability in rat. The most potent analog, 3-(5-aminocarbonylpyridyl piperidine 53j, displayed excellent DPP-4 activity with good selectivity versus other proline enzymes.Published by Elsevier Ltd.