Lead optimization of isocytosine-derived xanthine oxidase inhibitors

被引：33

作者：

Bajaj, Komal ^{[1
]}

Burudkar, Sandeep ^{[1
]}

Shah, Pranay ^{[1
]}

Keche, Ashish ^{[1
]}

Ghosh, Usha ^{[1
]}

Tannu, Prashant ^{[2
]}

Khanna, Smriti ^{[3
]}

Srivastava, Ankita ^{[4
]}

Deshmukh, Nitin J. ^{[5
]}

Dixit, Amol ^{[5
]}

Ahire, Yogesh ^{[5
]}

Damre, Anagha ^{[2
]}

Nemmani, Kumar V. S. ^{[5
]}

Kulkarni-Almeida, Asha ^{[4
]}

B-Rao, Chandrika ^{[3
]}

Sharma, Rajiv ^{[1
]}

Sivaramakrishnan, H. ^{[1
]}

机构：

[1] Piramal Healthcare Ltd, Dept Med Chem, Bombay 400063, Maharashtra, India

[2] Piramal Healthcare Ltd, Dept Drug Metab & Pharmacokinet, Bombay 400063, Maharashtra, India

[3] Piramal Healthcare Ltd, Discovery Informat, Bombay 400063, Maharashtra, India

[4] Piramal Healthcare Ltd, Dept High Throughput Screening & Biotechnol, Bombay 400063, Maharashtra, India

[5] Piramal Healthcare Ltd, Dept Pharmacol, Bombay 400063, Maharashtra, India

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 03期

关键词：

Xanthine oxidase inhibitors; Isocytosine; Structure-activity relationship; Docking; Pharmacokinetics; GOUT;

D O I：

10.1016/j.bmcl.2012.11.057

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We report our attempts at improving the oral efficacy of low-nanomolar inhibitors of xanthine oxidase from isocytosine series through chemical modifications. Our lead compound had earlier shown good in vivo efficacy when administered intraperitoneally but not orally. Several modifications are reported here which achieved more than twofold improvement in exposure. A compound with significant improvement in oral efficacy was also obtained. (c) 2012 Elsevier Ltd. All rights reserved.

引用

页码：834 / 838

页数：5

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