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Bioorg Med Chem Lett. 2005 May 16;15(10):2441-5.

1-((S)-gamma-substituted prolyl)-(S)-2-cyanopyrrolidine as a novel series of highly potent DPP-IV inhibitors.

Author information

1
Pharmaceuticals Research Unit, Research & Development Division, Mitsubishi Pharma Corporation, 1000, Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan.

Abstract

1-(Gamma-substituted prolyl)-(S)-2-cyanopyrrolidines were designed based on the predicted binding mode of the known DPP-IV inhibitor NVP-DPP728 and evaluated for their inhibitory activity. In structure-activity relationship study at the gamma-position of proline, it became clear that compounds bearing (S)-stereochemistry were 20-fold more potent than the antipode. Of these compounds, the (3,4-dicyanophenyl)amino- and (3-chloro-4-cyanophenyl)amino-derivatives showed the highest inhibitory activity.

PMID:
15863294
DOI:
10.1016/j.bmcl.2005.03.077
[Indexed for MEDLINE]

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