Synthesis and structure-activity relationships of potent 1-(2-substituted-aminoacetyl)-4-fluoro-2-cyanopyrrolidine dipeptidyl peptidase IV inhibitors

被引：12

作者：

Fukushima, Hiroshi ^{[1
]}

Hiratate, Akira ^{[1
]}

Takahashi, Masato ^{[1
]}

Saito-Hori, Masako ^{[2
]}

Munetomo, Eiji ^{[2
]}

Kitano, Kiyokazu ^{[2
]}

Saito, Hidetaka ^{[3
]}

Takaoka, Yuji

Yamamoto, Koji ^{[2
]}

机构：

[1] Taisho Pharmaceut Co Ltd, Med Chem Labs, Kita Ku, Saitama 3319530, Japan

[2] Taisho Pharmaceut Co Ltd, Mol Funct & Pharmacol Labs, Kita Ku, Saitama 3319530, Japan

[3] Taisho Pharmaceut Co Ltd, Nonclin Qual Assurance Sect, Kita Ku, Saitama 3319530, Japan

来源：

CHEMICAL & PHARMACEUTICAL BULLETIN | 2008年 / 56卷 / 08期

关键词：

dipeptidyl peptidase IV; inhibitors; fluoropyrrolidine; diabetes;

D O I：

10.1248/cpb.56.1110

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Dipeptidyl peptidase IV (DPP-IV) inhibitors have attracted attention as potential drugs for use in the treatment of type 2 diabetes because they prevent the degradation of glucagon-like peptide-1 (GLP-1) and extend its duration of action. We previously reported that 2-cyano-4-fluoropyrrolidines act as potent DPP-IV inhibitors and have been modifying the 1-position of pyrrolidine to obtain more useful inhibitors. An L-tert-butylglycine derivative was found to be a stable and potent DPP-IV inhibitor that exhibits a glucose lowering effect in vivo. Here, we report the synthesis of and biological data on the aforementioned derivatives.

引用

页码：1110 / 1117

页数：8

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