100008-30-8Relevant articles and documents
HTS followed by NMR based counterscreening. Discovery and optimization of pyrimidones as reversible and competitive inhibitors of xanthine oxidase
Even?s, Johan,Edfeldt, Fredrik,Lepist?, Matti,Svitacheva, Naila,Synnergren, Anna,Lundquist, Britta,Gr?nse, Mia,R?nnholm, Anna,Varga, Mikael,Wright, John,Wei, Min,Yue, Sherrie,Wang, Junfeng,Li, Chong,Li, Xuan,Chen, Gang,Liao, Yong,Lv, Gang,Tj?rnebo, Ann,Narjes, Frank
supporting information, p. 1315 - 1321 (2014/03/21)
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.
REGIOSPECIFIC SYNTHESIS OF N-1 AND N-2 SUBSTITUTED PYRIMIDONES EMPLOYING A NOVEL 1,3-OXAZINE PREPARATION
Skulnic, Harvey I.,Wierenga, Wendell
, p. 1685 - 1689 (2007/10/02)
Reaction of ethyl benzoylacetate with methylthiopseudourea resulted in expulsion of methylmercaptan to afford 2-amino-6-phenyl-4H-1,3-oxazin-4-one in good yield.This novel oxazine synthesis was exploited to secure N-1 and N-2 substituted pyrimidinones regiospecifically.
