Design, synthesis and biological evaluation of 7-nitro-1H-indole-2-carboxylic acid derivatives as allosteric inhibitors of fructose-1,6-bisphosphatase

被引：27

作者：

Bie, Jianbo

Liu, Shuainan

Zhou, Jie

Xu, Bailing ^{[1
]}

Shen, Zhufang

机构：

[1] Chinese Acad Med Sci, Inst Mat Med, Beijing Key Lab Act Substance Discovery & Druggab, Beijing 100050, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2014年 / 22卷 / 06期

基金：

北京市自然科学基金;

关键词：

Fructose-1; 6-Bisphosphatase inhibitor; Allosteric inhibitor; Indole; Diabetes; HUMAN LIVER FRUCTOSE-1,6-BISPHOSPHATASE; FRUCTOSE 1,6-BISPHOSPHATASE INHIBITORS; AMP MIMICS; GLUCOSE-PRODUCTION; RAT-LIVER; DISCOVERY; BINDING; SERIES; HYPERGLYCEMIA; PRODRUGS;

D O I：

10.1016/j.bmc.2014.01.047

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 novel indole derivatives was synthesized as inhibitors of fructose-1,6-bisphosphatase (FBPase). Extensive structure-activity relationships were conducted and led to a potent FBPase inhibitor 3.9 with an IC50 of 0.99 mu M. The binding mode of this series of indoles was predicted using CDOCKER algorithm. The results of this research will shed light on the further design and optimization of novel small molecules as FBPase inhibitors. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：1850 / 1862

页数：13

共 29 条

[1]

BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3

[2]

Dang Q., 2007, United States Patent, Patent No. [US0225259, 0225259, 225259 Al [P], 225259]

[3] Discovery of phosphonic diamide prodrugs and their use for the oral delivery of a series of fructose 1,6-bisphosphatase inhibitors [J].

Dang, Qun ;

Kasibhatla, Srinivas Rao ;

Jiang, Tao ;

Fan, Kevin ;

Liu, Yan ;

Taplin, Frank ;

Schulz, William ;

Cashion, Daniel K. ;

Reddy, K. Raja ;

van Poelje, Paul D. ;

Fujitaki, James M. ;

Potter, Scott C. ;

Erion, Mark D. .

JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (14) :4331-4339

[4] Discovery of potent and specific fructose-1,6-bisphosphatase inhibitors and a series of orally-bioavailable phosphoramidase-sensitive prodrugs for the treatment of type 2 diabetes [J].

Dang, Qun ;

Kasibhatla, Srinivas Rao ;

Reddy, K. Raja ;

Jiang, Tao ;

Reddy, M. Rami ;

Potter, Scott C. ;

Fujitaki, James M. ;

van Poelje, Paul D. ;

Huang, Jingwei ;

Lipscomb, William N. ;

Erion, Mark D. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2007, 129 (50) :15491-15502

[5] Discovery of a Series of Phosphonic Acid-Containing Thiazoles and Orally Bioavailable Diamide Prodrugs That Lower Glucose in Diabetic Animals Through Inhibition of Fructose-1,6-Bisphosphatase [J].

Dang, Qun ;

Liu, Yan ;

Cashion, Daniel K. ;

Kasibhatla, Srinivas Rao ;

Jiang, Tao ;

Taplin, Frank ;

Jacintho, Jason D. ;

Li, Haiqing ;

Sun, Zhili ;

Fan, Yi ;

DaRe, Jay ;

Tian, Feng ;

Li, Wenyu ;

Gibson, Tony ;

Lemus, Robert ;

van Poelje, Paul D. ;

Potter, Scott C. ;

Erion, Mark D. .

JOURNAL OF MEDICINAL CHEMISTRY, 2011, 54 (01) :153-165

[6] Fructose-1,6-bisphosphatase Inhibitors. 2. Design, Synthesis, and Structure-Activity Relationship of a Series of Phosphonic Acid Containing Benzimidazoles that Function as 5′-Adenosinemonophosphate (AMP) Mimics [J].

Dang, Qun ;

Kasibhatla, Srinivas Rao ;

Xiao, Wei ;

Liu, Yan ;

DaRe, Jay ;

Taplin, Frank ;

Reddy, K. Raja ;

Scarlato, Gerard R. ;

Gibson, Tony ;

van Poelje, Paul D. ;

Potter, Scott C. ;

Erion, Mark D. .

JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (01) :441-451

[7] Fructose-1,6-bisphosphatase Inhibitors. 1. Purine Phosphonic Acids as Novel AMP Mimics [J].

Dang, Qun ;

Brown, Brian S. ;

Liu, Yan ;

Rydzewski, Robert M. ;

Robinson, Edward D. ;

van Poelje, Paul D. ;

Reddy, M. Rami ;

Erion, Mark D. .

JOURNAL OF MEDICINAL CHEMISTRY, 2009, 52 (09) :2880-2898

[8]

ELMAGHRABI MR, 1993, J BIOL CHEM, V268, P9466

[9] Structure-guided design of AMP mimics that inhibit fructose-1,6-bisphosphatase with high affinity and specificity [J].

Erion, Mark D. ;

Dang, Qun ;

Reddy, M. Rami ;

Kasibhatla, Srinivas Rao ;

Huang, Jingwei ;

Lipscomb, William N'. ;

van Poelje, Paul D. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2007, 129 (50) :15480-15490

[10] POSTPRANDIAL HYPERGLYCEMIA IN PATIENTS WITH NONINSULIN-DEPENDENT DIABETES-MELLITUS - ROLE OF HEPATIC AND EXTRAHEPATIC TISSUES [J].

FIRTH, RG ;

BELL, PM ;

MARSH, HM ;

HANSEN, I ;

RIZZA, RA .

JOURNAL OF CLINICAL INVESTIGATION, 1986, 77 (05) :1525-1532

← 1 2 3 →