1415309-81-7Relevant articles and documents
Isocytosine-based inhibitors of xanthine oxidase: Design, synthesis, SAR, PK and in vivo efficacy in rat model of hyperuricemia
Khanna, Smriti,Burudkar, Sandeep,Bajaj, Komal,Shah, Pranay,Keche, Ashish,Ghosh, Usha,Desai, Avani,Srivastava, Ankita,Kulkarni-Almeida, Asha,Deshmukh, Nitin J.,Dixit, Amol,Brahma, Manoja K.,Bahirat, Umakant,Doshi, Lalit,Nemmani, Kumar V.S.,Tannu, Prashant,Damre, Anagha,B-Rao, Chandrika,Sharma, Rajiv,Sivaramakrishnan
, p. 7543 - 7546 (2013/02/22)
Structure-activity relationship studies were carried out for lead generation following structure-guided design approach from an isocytosine scaffold identified earlier for xanthine oxidase inhibition. A 470-fold improvement in in vitro IC50 was obtained in the process. Five most potent compounds with nanomolar IC50 values were selected for pharmacokinetics and in vivo experiments. The best compound showed good in vivo activity when administered intraperitoneally but was not active by oral route. The results suggest that improvement in oral exposure could improve the in vivo efficacy of this series.
