Synthesis and evaluation of pyrazolo[3,4-b] pyridines and its structural analogues as TNF-α and IL-6 inhibitors

被引：104

作者：

Bharate, Sandip B. ^{[1
]}

Mahajan, Tushar R. ^{[1
]}

Gole, Yogesh R. ^{[1
]}

Nambiar, Mahesh ^{[2
]}

Matan, T. T. ^{[2
]}

Kulkarni-Almeida, Asha ^{[2
]}

Balachandran, Sarala ^{[1
]}

Junjappa, H. ^{[1
]}

Balakrishnan, Arun ^{[2
]}

Vishwakarma, Ram A. ^{[1
]}

机构：

[1] Piramal Life Sci Ltd, Dept Med Chem, Mumbai 400063, Maharashtra, India

[2] Piramal Life Sci Ltd, Dept Screening & Biotechnol, Mumbai 400063, Maharashtra, India

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 15期

关键词：

pyrazolo[3,4-b]pyridines; anti-inflammatory; TNF-alpha; IL-6;

D O I：

10.1016/j.bmc.2008.06.042

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：

In the present article, we have synthesized three different series of pyrazolo[3,4-b] pyridines and their structural analogues using novel synthetic strategy involving one-pot condensation of 5,6-dihydro-4H-pyran-3-carbaldehyde/2-formyl-3,4,6-tri-O-methyl-D-glucal/chromone-3-carbaldehyde with heteroaromatic amines. All synthesized compounds were evaluated for their anti-inflammatory activity against TNF-alpha and IL-6. Out of 28 compounds screened, 40, 51, 52 and 56 exhibited promising activity against IL-6 with 60-65% inhibition at 10 mu M concentration. Amongst these, 51, 52 and 56 showed potent IL-6 inhibitory activity with IC50's of 0.2, 0.3 and 0.16 mu M, respectively. Compound 56 was not cytotoxic in CCK-8 cells up to the concentration of > 100 mu M. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：7167 / 7176

页数：10

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