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Lead optimization of isocytosine-derived xanthine oxidase inhibitors |
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| Authors: | 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 VS Nemmani Asha Kulkarni-Almeida Chandrika B-Rao Rajiv Sharma H Sivaramakrishnan |
| Institution: | 1. Department of Medicinal Chemistry, Piramal Healthcare Limited, Goregaon (E), Mumbai 400 063, Maharashtra, India;2. Department of Drug Metabolism and Pharmacokinetics, Piramal Healthcare Limited, Goregaon (E), Mumbai 400 063, Maharashtra, India;3. Discovery Informatics, Piramal Healthcare Limited, Goregaon (E), Mumbai 400 063, Maharashtra, India;4. Department of High Throughput Screening and Biotechnology, Piramal Healthcare Limited, Goregaon (E), Mumbai 400 063, Maharashtra, India;5. Department of Pharmacology, Piramal Healthcare Limited, Goregaon (E), Mumbai 400 063, Maharashtra, India |
| 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. |
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