Design and synthesis of new potent dipeptidyl peptidase IV inhibitors with enhanced ex vivo duration

被引：18

作者：

Kondo, Takashi ^{[1
]}

Nekado, Takahiro ^{[1
]}

Sugimoto, Isamu ^{[1
]}

Ochi, Kenya ^{[1
]}

Takai, Shigeyuki ^{[1
]}

Kinoshita, Atsushi ^{[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, Osaka 6188585, Japan

来源：

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

关键词：

DPP-IV inhibitor; protyl-2-cyanopyrrolidine;

D O I：

10.1016/j.bmc.2007.01.041

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of 5 beta-methylprolyl-2-cyanopyrrolidine analogs were synthesized and evaluated as DPP-IV inhibitors, and the duration of their ex vivo activity was assessed. Comparison of their potency and duration of action was done among three different species. The mode of binding was investigated, and the effect on the plasma glucose level was evaluated. Structure-activity relationships are also presented. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：2631 / 2650

页数：20

共 24 条

[1] Design and synthesis of long-acting inhibitors of dipeptidyl peptidase IV
Kondo, Takashi
Sugimoto, Isamu
Nekado, Takahiro
Ochi, Kenya
Ohtani, Tazumi
Tajima, Yohei
Yamamoto, Susumu
Kawabata, Kazuhito
Nakai, Hisao
Toda, Masaaki
BIOORGANIC & MEDICINAL CHEMISTRY, 2007, 15 (07) : 2715 - 2735
[2] Discovery of potent dipeptidyl peptidase IV inhibitors through pharmacophore hybridization and hit-to-lead optimization
Zeng, Shaogao
Xie, Hui
Zeng, Li-li
Lu, Xin
Zhao, Xin
Zhang, Gui-cheng
Tu, Zheng-chao
Xu, Hong-jiang
Yang, Ling
Zhang, Xi-quan
Hu, Wenhui
BIOORGANIC & MEDICINAL CHEMISTRY, 2013, 21 (07) : 1749 - 1755
[3] Novel pyrrolopyrimidine analogues as potent dipeptidyl peptidase IV inhibitors based on pharmacokinetic property-driven optimization
Xie, Hui
Zeng, Lili
Zeng, Shaogao
Lu, Xin
Zhang, Guicheng
Zhao, Xin
Cheng, Na
Tu, Zhengchao
Li, Zhiyuan
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Yang, Ling
Zhang, Xiquan
Huang, Min
Zhao, Junling
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EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2012, 52 : 205 - 212
[4] Highly potent dipeptidyl peptidase IV inhibitors derived from Alogliptin through pharmacophore hybridization and lead optimization
Xie, Hui
Zeng, Lili
Zeng, Shaogao
Lu, Xin
Zhao, Xin
Zhang, Guicheng
Tu, Zhengchao
Xu, Hongjiang
Yang, Ling
Zhang, Xiquan
Wang, Shanchun
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EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2013, 68 : 312 - 320
[5] The therapeutic potential of inhibitors of dipeptidyl peptidase IV (DPP IV) and related proline-specific dipeptidyl aminopeptidases
Augustyns, K
Van der Veken, P
Senten, K
Haemers, A
CURRENT MEDICINAL CHEMISTRY, 2005, 12 (08) : 971 - 998
[6] 6-Imino-2-thioxo-pyrimidinones as a new class of dipeptidyl peptidase IV inhibitors
Dubravko Jelić
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Višnja Stepanić
Krunoslav Kovačević
Donatella Verbanac
Medicinal Chemistry Research, 2011, 20 : 339 - 345
[7] 6-Imino-2-thioxo-pyrimidinones as a new class of dipeptidyl peptidase IV inhibitors
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Nujic, Krunoslav
Stepanic, Visnja
Kovacevic, Krunoslav
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MEDICINAL CHEMISTRY RESEARCH, 2011, 20 (03) : 339 - 345
[8] The highly potent and selective dipeptidyl peptidase IV inhibitors bearing a thienopyrimidine scaffold effectively treat type 2 diabetes
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Peng, Li
Zhang, Guicheng
Lan, Xiaobing
Li, Chufang
Chen, Fuxin
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Lin, Zuoxian
Chen, Ling
Dai, Renke
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Yang, Ling
Zhang, Xiquan
Hu, Wenhui
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2011, 46 (01) : 71 - 76
[9] A new screening method based on yeast-expressed human dipeptidyl peptidase IV and discovery of novel inhibitors
Chen-Xi Hu
Hui Huang
Li Zhang
You Huang
Zhu-Fang Shen
Ke-Di Cheng
Guan-Hua Du
Ping Zhu
Biotechnology Letters, 2009, 31 : 979 - 984
[10] A new screening method based on yeast-expressed human dipeptidyl peptidase IV and discovery of novel inhibitors
Hu, Chen-Xi
Huang, Hui
Zhang, Li
Huang, You
Shen, Zhu-Fang
Cheng, Ke-Di
Du, Guan-Hua
Zhu, Ping
BIOTECHNOLOGY LETTERS, 2009, 31 (07) : 979 - 984

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