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Synthesis and structure-activity relationships of potent 4-fluoro-2-cyanopyrrolidine dipeptidyl peptidase IV inhibitors.

Abstract：

:Dipeptidyl peptidase IV (DPP-IV) inhibitors are promising antidiabetic drugs, and several drugs are in the developmental stage. We previously reported that the introduction of fluorine to the 4-position of 2-cyanopyrrolidine enhanced the DPP-IV inhibitory effect. In the present report, we examined the structure-activity relationship (SAR) of 2-cyano-4-fluoropyrrolidine with N-substituted glycine at the 1-position. We report the identification of a potent and stable DPP-IV inhibitor (TS-021) with a long-term persistent plasma drug concentration and a potent antihyperglycemic activity.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Fukushima H,Hiratate A,Takahashi M,Mikami A,Saito-Hori M,Munetomo E,Kitano K,Chonan S,Saito H,Suzuki A,Takaoka Y,Yamamoto K

doi

10.1016/j.bmc.2008.01.016

subject

Has Abstract

pub_date

2008-04-01 00:00:00

pages

4093-106

issue

7

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(08)00033-3

journal_volume

16

pub_type

杂志文章

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