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Design, synthesis, and pharmacological evaluation of quinazoline derivatives as novel and potent pan-JAK inhibitors.
Xiang, Jinbao; Wang, Yuji; Wang, Wanhe; Yu, Jianxin; Zheng, Lianyou; Hong, Yuan; Shi, Lingling; Zhang, Chunling; Chen, Na; Xu, Jia; Gong, Xuelian; Zhang, Zhuoqi; Cui, Hongming; Zhou, Qian; Zhang, Dapeng; Liu, Yanjun; Ke, Ying; Shen, Jingkang; Xia, Guangxin; Bai, Xu.
Afiliação
  • Xiang J; The Center for Combinatorial Chemistry and Drug Discovery of Jilin University, The School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130021, PR China.
  • Wang Y; Central Research Institute, National Key Laboratory of Innovative Immunotherapy, Shanghai Pharmaceuticals Holding Co., Ltd., Shanghai 201203, PR China.
  • Wang W; The Center for Combinatorial Chemistry and Drug Discovery of Jilin University, The School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130021, PR China.
  • Yu J; Central Research Institute, National Key Laboratory of Innovative Immunotherapy, Shanghai Pharmaceuticals Holding Co., Ltd., Shanghai 201203, PR China.
  • Zheng L; The Center for Combinatorial Chemistry and Drug Discovery of Jilin University, The School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130021, PR China.
  • Hong Y; Central Research Institute, National Key Laboratory of Innovative Immunotherapy, Shanghai Pharmaceuticals Holding Co., Ltd., Shanghai 201203, PR China.
  • Shi L; The Center for Combinatorial Chemistry and Drug Discovery of Jilin University, The School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130021, PR China.
  • Zhang C; The Center for Combinatorial Chemistry and Drug Discovery of Jilin University, The School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130021, PR China.
  • Chen N; Central Research Institute, National Key Laboratory of Innovative Immunotherapy, Shanghai Pharmaceuticals Holding Co., Ltd., Shanghai 201203, PR China.
  • Xu J; Central Research Institute, National Key Laboratory of Innovative Immunotherapy, Shanghai Pharmaceuticals Holding Co., Ltd., Shanghai 201203, PR China.
  • Gong X; Central Research Institute, National Key Laboratory of Innovative Immunotherapy, Shanghai Pharmaceuticals Holding Co., Ltd., Shanghai 201203, PR China.
  • Zhang Z; The Center for Combinatorial Chemistry and Drug Discovery of Jilin University, The School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130021, PR China.
  • Cui H; The Center for Combinatorial Chemistry and Drug Discovery of Jilin University, The School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130021, PR China.
  • Zhou Q; The Center for Combinatorial Chemistry and Drug Discovery of Jilin University, The School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130021, PR China.
  • Zhang D; The Center for Combinatorial Chemistry and Drug Discovery of Jilin University, The School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130021, PR China.
  • Liu Y; Central Research Institute, National Key Laboratory of Innovative Immunotherapy, Shanghai Pharmaceuticals Holding Co., Ltd., Shanghai 201203, PR China.
  • Ke Y; Central Research Institute, National Key Laboratory of Innovative Immunotherapy, Shanghai Pharmaceuticals Holding Co., Ltd., Shanghai 201203, PR China.
  • Shen J; Central Research Institute, National Key Laboratory of Innovative Immunotherapy, Shanghai Pharmaceuticals Holding Co., Ltd., Shanghai 201203, PR China.
  • Xia G; Central Research Institute, National Key Laboratory of Innovative Immunotherapy, Shanghai Pharmaceuticals Holding Co., Ltd., Shanghai 201203, PR China. Electronic address: xiagx@sphchina.com.
  • Bai X; The Center for Combinatorial Chemistry and Drug Discovery of Jilin University, The School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130021, PR China. Electronic address: xbai@jlu.edu.cn.
Bioorg Chem ; 140: 106765, 2023 11.
Article em En | MEDLINE | ID: mdl-37582330
Janus kinases (JAKs) play a critical role in modulating the function and expression of inflammatory cytokines related to rheumatoid arthritis (RA). Herein, we report the design, synthesis, and structure-activity relationships (SARs) of a series of novel quinazoline derivatives as JAK inhibitors. Among these inhibitors, compound 11n showed high potency against JAKs (JAK1/JAK2/JAK3/TYK2, IC50 = 0.40, 0.83, 2.10, 1.95 nM), desirable metabolic characters, and excellent pharmacokinetic properties. In collagen-induced arthritis (CIA) models, compound 11n exhibited significant reduction in joint swelling with good safety, which could be served as a potential therapeutic candidate for the treatment of inflammatory diseases.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Artrite Reumatoide / Inibidores de Janus Quinases Limite: Humans Idioma: En Revista: Bioorg Chem Ano de publicação: 2023 Tipo de documento: Article
Texto completo
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XML
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Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Artrite Reumatoide / Inibidores de Janus Quinases Limite: Humans Idioma: En Revista: Bioorg Chem Ano de publicação: 2023 Tipo de documento: Article