Document Detail

HTS followed by NMR based counterscreening. Discovery and optimization of pyrimidones as reversible and competitive inhibitors of xanthine oxidase.
MedLine Citation:
PMID:  24508129     Owner:  NLM     Status:  Publisher    
The identification of novel, non-purine based inhibitors of xanthine oxidase is described. After a high-throughput screening campaign, an NMR based counterscreen was used to distinguish actives, which interact with XO in a reversible manner, from assay artefacts. This approach identified pyrimidone 1 as a reversible and competitive inhibitor with good lead-like properties. A hit to lead campaign gave compound 41, a nanomolar inhibitor of hXO with efficacy in the hyperuricemic rat model after oral dosing.
Johan Evenäs; Fredrik Edfeldt; Matti Lepistö; Naila Svitacheva; Anna Synnergren; Britta Lundquist; Mia Gränse; Anna Rönnholm; Mikael Varga; John Wright; Min Wei; Sherrie Yue; Junfeng Wang; Chong Li; Xuan Li; Gang Chen; Yong Liao; Gang Lv; Ann Tjörnebo; Frank Narjes
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-1-28
Journal Detail:
Title:  Bioorganic & medicinal chemistry letters     Volume:  -     ISSN:  1464-3405     ISO Abbreviation:  Bioorg. Med. Chem. Lett.     Publication Date:  2014 Jan 
Date Detail:
Created Date:  2014-2-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9107377     Medline TA:  Bioorg Med Chem Lett     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014 Elsevier Ltd. All rights reserved.
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