Identification of novel urea derivatives as PTP1B inhibitors: synthesis, biological evaluation and structure-activity relationships

被引：10

作者：

Gupta, Swati ^{[1
]}

Varshney, Kanika ^{[1
]}

Srivastava, Rohit ^{[2
]}

Rahuja, Neha ^{[2
]}

Rawat, Arun K. ^{[2
]}

Srivastava, Arvind K. ^{[2
]}

Saxena, Anil K. ^{[1
]}

机构：

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

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

来源：

MEDCHEMCOMM | 2013年 / 4卷 / 10期

关键词：

TYROSINE-PHOSPHATASE; 1B; INSULIN SENSITIVITY; RESISTANCE; OBESITY; DISCOVERY; DESIGN;

D O I：

10.1039/c3md00138e

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：

The protein tyrosine phosphatase 1B (PTP1B) is an attractive target for the treatment of type 2 diabetes. A series of substituted 1,3-benzyl urea has been synthesized and evaluated for PTP1B inhibitory, antidiabetic and antidyslipidemic activities. The most active compound of the series 5b showed 79.4% PTP1B inhibition and 20.7% blood glucose lowering in the STZ model. It also lowered the serum cholesterol level by 16.3% and significantly increased the serum HDL-cholesterol by 46.8%. The high activity of compound 5b has been explained by docking studies.

引用

页码：1382 / 1387

页数：6

共 22 条

[1]

[Anonymous], GOLD VERS 3 1

[2] A novel synthesis of disubstituted ureas using titanium(IV) isopropoxide and sodium borohydride [J].

Armstrong, JD ;

Wolfe, CN ;

Keller, JL ;

Lynch, J ;

Bhupathy, M ;

Volante, RP ;

DeVita, RJ .

TETRAHEDRON LETTERS, 1997, 38 (09) :1531-1532

[3] Recent Advances in the Discovery of Competitive Protein Tyrosine Phosphatase 1B Inhibitors for the Treatment of Diabetes, Obesity, and Cancer [J].

Combs, Andrew P. .

JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (06) :2333-2344

[4] 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

[5] Identification of Novel Amino Acid Derived CCK-2R Antagonists As Potential Antiulcer Agent: Homology Modeling, Design, Synthesis, and Pharmacology [J].

Gupta, Amit K. ;

Varshney, Kanika ;

Singh, Neetu ;

Mishra, Vaibhav ;

Saxena, Mridula ;

Palit, Gautam ;

Saxena, Anil K. .

JOURNAL OF CHEMICAL INFORMATION AND MODELING, 2013, 53 (01) :176-187

[6] Design, synthesis and docking studies on phenoxy-3-piperazin-1-yl-propan-2-ol derivatives as protein tyrosine phosphatase 1B inhibitors [J].

Gupta, Swati ;

Pandey, Gyanendra ;

Rahuja, Neha ;

Srivastava, Arvind K. ;

Saxena, Anil K. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (19) :5732-5734

[7] Highly selective aldose reductase inhibitors .1. 3-(Arylalkyl)-2,4,5-trioxoimidazolidine-1-acetic acids [J].

Ishii, A ;

Kotani, T ;

Nagaki, Y ;

Shibayama, Y ;

Toyomaki, Y ;

Okukado, N ;

Ienaga, K ;

Okamoto, K .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (09) :1924-1927

[8] Protein tyrosine phosphatase 1B inhibitors for diabetes [J].

Johnson, TO ;

Ermolieff, J ;

Jirousek, MR .

NATURE REVIEWS DRUG DISCOVERY, 2002, 1 (09) :696-709

[9]

Kenny SJ., 1995, Diabetes in America, P47

[10] Increased energy expenditure, decreased adiposity, and tissue-specific insulin sensitivity in protein-tyrosine phosphatase 1B-deficient mice [J].

Klaman, LD ;

Boss, O ;

Peroni, OD ;

Kim, JK ;

Martino, JL ;

Zabolotny, JM ;

Moghal, N ;

Lubkin, M ;

Kim, YB ;

Sharpe, AH ;

Stricker-Krongrad, A ;

Shulman, GI ;

Neel, BG ;

Kahn, BB .

MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (15) :5479-5489

← 1 2 3 →