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Discovery of novel 1,2,4-triazole derivatives as xanthine oxidoreductase inhibitors with hypouricemic effects.
Yang, Yajun; Yan, Dingan; Cheng, Hanzeng; Nan, Guanglei; Hou, Xianxin; Ren, Long; Yang, Ying; Li, Xuechen; Tian, Jinying; Ye, Fei; Xiao, Zhiyan.
Afiliação
  • Yang Y; Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
  • Yan D; Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
  • Cheng H; Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
  • Nan G; Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
  • Hou X; Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
  • Ren L; Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
  • Yang Y; Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
  • Li X; Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
  • Tian J; Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
  • Ye F; Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address: yefei@imm.ac.cn.
  • Xiao Z; Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address: xiaoz@imm.ac.cn.
Bioorg Chem ; 129: 106162, 2022 Dec.
Article em En | MEDLINE | ID: mdl-36183564
ABSTRACT
Xanthine oxidoreductase (XOR) is a clinically validated target for the treatment of hyperuricemia and gout. A series of novel 1,2,4-triazoles were identified as potent XO inhibitors via a fused-pharmacophore strategy based on the interaction modes of febuxostat and topiroxostat. Among them, compound 7i showed an IC50 value of 0.20 nM against XOR, which was superior to febuxostat and topiroxostat. Furthermore, 7i exhibited significant hypouricemic and serum XOR inhibitory effects in potassium oxonate induced hyperuricemia mouse models. A single-dose toxicity assessment of 7i showed no noticeable toxicity at the dose of 50 mg/kg. These results demonstrated that 7i could be a promising lead compound for the treatment of hyperuricemia and gout.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Hiperuricemia / Gota Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
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PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Hiperuricemia / Gota Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article