Design and synthesis of long-acting inhibitors of dipeptidyl peptidase IV

被引：22

作者：

Kondo, Takashi ^{[1
]}

Sugimoto, Isamu ^{[1
]}

Nekado, Takahiro ^{[1
]}

Ochi, Kenya ^{[1
]}

Ohtani, Tazumi ^{[1
]}

Tajima, Yohei ^{[1
]}

Yamamoto, Susumu ^{[1
]}

Kawabata, Kazuhito ^{[1
]}

Nakai, Hisao ^{[1
]}

Toda, Masaaki ^{[1
]}

机构：

[1] Ono Pharmaceut Co Ltd, Minase Res Inst, 3-1-1 Sakurai,Shimamoto Cho, Osaka 6188585, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2007年 / 15卷 / 07期

关键词：

DPP-IV inhibitor; prolylprolinenitriles; glucuronate; GLYCOSIDASE INHIBITORS; POSTPRANDIAL GLUCOSE; HIGHLY POTENT; DRUG-THERAPY; INSULIN; PREVALENCE; DISCOVERY; LIGANDS; LAF237; PERIOD;

D O I：

10.1016/j.bmc.2007.01.033

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

A series of (4-substituted prolyl)prolinenitriles were synthesized and evaluated as inhibitors of dipeptidylpeptidase IV (DPP-IV). Among those tested, the 40-[4-(hydroxyphenyl)prolyl]prolinenitriles showed a potent inhibitory activity with a long duration of action. Metabolic formation of the corresponding phenol glucuronates was found to contribute to their long duration of action. The activity profiles of the synthesized compounds are reported and structure-activity relationships are also presented. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：2715 / 2735

页数：21

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