Synthesis Of Non - Cloth And Its Analogues And Inhibition Of Xanthine Oxidase Activity

The pathogenesis of gout and action mechanisms of drugs for its treatment are introduced briefly, and the recent advances of xanthine oxidase inhibitors(XOIs) are described in detail in this paper.Based on the interaction modes of Febuxostat and Y-700 as potent XOIs at the active site of xanthine oxidase and their structure-activity relationships, a series of 5-phenyl-3-isoxazole carboxylic acid derivatives were designed through replacing the corresponding five-membered heterocyclic rings with isoxazole, together with the essential carboxylic group at its 3-position, at the same time, cyano, nitro, iodine and alkoxyl groups were also introduced at the meta and para positions of phenyl ring respectively, and with the effort to find new XOIs with better activities.Starting from 4-hydroxyacetophenone, five compounds with nitro group and one compound with iodine group were synthesized via a series of reactions like nitration or iodination, alkylation, condensation, cyclization and hydrolysis, and six cyano substituted compounds were obtained through a 6-step procedure including iodination, alkylation, cyanidation, condensation, cyclization and hydrolysis. The 12 synthesized compounds had not been reported in literature, and their structures were confirmed by’H-NMR and IR spectra, and one compound(CJR-001) was also characterized by 13C-NMR、DEPT、HMQC、MS and X-ray single crystal diffraction. The in vitro inhibitory activities were evaluated on xanthine oxidase from bovine,9 compounds showed good inhibitory activities with IC50S ranging from 0.36μM to 12.75μM, CJR-007 exhibited the strongest activity with an IC50 of 0.36μM, nevertheless, they were weaker than Febuxostat with an IC50 of 3nM.At the same time, a novel synthetic route for Febuxostat with advantages like facile raw materials, convenient operations, relatively higher yield, and higher purity of the end product, was also given in this paper.