Synthesis of novel benzofuran isoxazolines as protein tyrosine phosphatase 1B inhibitors

被引：41

作者：

Ahmad, G

Mishra, PK

Gupta, P

Yadav, PP

Tiwari, P

Tamrakar, AK

Srivastava, AK

Maurya, R ^{[1
]}

机构：

[1] Cent Drug Res Inst, Med & Proc Chem Div, Lucknow 226001, Uttar Pradesh, India

[2] Cent Drug Res Inst, Div Biochem, Lucknow 226001, Uttar Pradesh, India

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 08期

关键词：

protein tyrosine phosphatases 1B inhibitors; isoxazolines; karanjic acid;

D O I：

10.1016/j.bmcl.2006.01.062

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

PTPases are considered to be involved in the etiology of diabetes mellitus and neural diseases, such as Alzheimer's disease and Parkinson's disease. Therefore, PTPase inhibitors should be useful tools to Study the role of PTPases in these diseases and other biological phenomena, and which can be developed into chemotherapeutic agents. In the present study, we have synthesized novel benzofuran isoxazolines 13-21 via 1,3-dipolar cycloaddition reaction using karanjin (1) and kanjone (2), isolated from Pongamia pinnata fruits. All the synthesized compounds were evaluated against PTPase enzyme. Compounds 19 and 20 displayed significant inhibitory activity with IC50 values 76 and 81 mu M, respectively. (C) 2006 Published by Elsevier Ltd.

引用

页码：2139 / 2143

页数：5

共 14 条

[1] Inhibition of dipeptidyl peptidase IV improves metabolic control over a 4-week study period in type 2 diabetes [J].

Ahrén, B ;

Simonsson, E ;

Larsson, H ;

Landin-Olsson, M ;

Torgeirsson, H ;

Jansson, PA ;

Sandqvist, M ;

Båvenholm, P ;

Efendic, S ;

Eriksson, JW ;

Dickinson, S ;

Holmes, D .

DIABETES CARE, 2002, 25 (05) :869-875

[2]

Blaskovich MA, 2002, EXPERT OPIN THER PAT, V12, P871

[3] Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene [J].

Elchebly, M ;

Payette, P ;

Michaliszyn, E ;

Cromlish, W ;

Collins, S ;

Loy, AL ;

Normandin, D ;

Cheng, A ;

Himms-Hagen, J ;

Chan, CC ;

Ramachandran, C ;

Gresser, MJ ;

Tremblay, ML ;

Kennedy, BP .

SCIENCE, 1999, 283 (5407) :1544-1548

[4] Tyrosine dephosphorylation and deactivation of insulin receptor substrate-1 by protein-tyrosine phosphatase 1B - Possible facilitation by the formation of a ternary complex with the GRB2 adaptor protein [J].

Goldstein, BJ ;

Bittner-Kowalczyk, A ;

White, MF ;

Harbeck, M .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (06) :4283-4289

[5] Investigation of potential bioisosteric replacements for the carboxyl groups of peptidomimetic inhibitors of protein tyrosine phosphatase 1B: Identification of a tetrazole-containing inhibitor with cellular activity [J].

Liljebris, C ;

Larsen, SD ;

Ogg, D ;

Palazuk, BJ ;

Bleasdale, JE .

JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (09) :1785-1798

[6] Fragment screening and assembly: A highly efficient approach to a selective and cell active protein tyrosine phosphatase 1B inhibitor [J].

Liu, G ;

Xin, ZL ;

Pei, ZG ;

Hajduk, PJ ;

Abad-Zapatero, C ;

Hutchins, CW ;

Zhao, HY ;

Lubben, TH ;

Ballaron, SJ ;

Haasch, DL ;

Kaszubska, W ;

Rondinone, CM ;

Trevillyan, JM ;

Jirousek, MR .

JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (20) :4232-4235

[7] Addition of nitrile oxides to germyl-substituted ethylenes [J].

Lukevics, E ;

Arsenyan, P ;

Belyakov, S ;

Popelis, J .

JOURNAL OF ORGANOMETALLIC CHEMISTRY, 1998, 558 (1-2) :155-161

[8]

MANDAL B, 1987, INDIAN ACTA PHYSL PH, V12, P42

[9]

MCCORMACK JC, 2000, CURR OPIN DRUG DISC, V3, P527

[10]

MUKERJEE SK, 1955, J CHEM SOC, P2048

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