Bioorganic & Medicinal Chemistry Letters 2013-02-01

Lead optimization of isocytosine-derived xanthine oxidase inhibitors.

Komal Bajaj, Sandeep Burudkar, Pranay Shah, Ashish Keche, Usha Ghosh, Prashant Tannu, Smriti Khanna, Ankita Srivastava, Nitin J Deshmukh, Amol Dixit, Yogesh Ahire, Anagha Damre, Kumar V S Nemmani, Asha Kulkarni-Almeida, Chandrika B-Rao, Rajiv Sharma, H Sivaramakrishnan

Index: Bioorg. Med. Chem. Lett. 23(3) , 834-8, (2013)

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Abstract

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.Copyright © 2012 Elsevier Ltd. All rights reserved.