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.

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Chen P, Caldwell CG, Ashton W, Wu JK, He H, Lyons KA, Thornberry NA, Weber AE

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.

Bioorg Med Chem Lett. 2011 Mar 15;21(6):1880-6. doi: 10.1016/j.bmcl.2010.12.060. Epub 2011 Jan 15.

PubMed ID

21320777 [ View in PubMed

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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.

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Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Sitagliptin	Dipeptidyl peptidase 4	IC 50 (nM)	18	N/A	N/A	Details