N-(2-chloro-5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)benzenesulfonamide | 1148008-25-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: N-(2-chloro-5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)benzenesulfonamide
• 英文别名: N-[2-chloro-5-(1-methylpyrazol-4-yl)pyridin-3-yl]benzenesulfonamide
• CAS: 1148008-25-6
• 化学式: C₁₅H₁₃ClN₄O₂S
• 分子量: 348.813
• InChiKey: ANBDBTPNGLARRQ-UHFFFAOYSA-N

物化性质

• 沸点：
  558.8±60.0 °C(predicted)
• 密度：
  1.44±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  85.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-氯-3-氨基-5-溴吡啶 在 吡啶 、 四(三苯基膦)钯 、 potassium acetate 作用下， 以 1,4-二氧六环 为溶剂， 反应 13.0h， 生成 N-(2-chloro-5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)benzenesulfonamide
  参考文献：
  名称：

  Discovery of 6′-chloro-N-methyl-5’-(phenylsulfonamido)-[3,3′-bipyridine]-5-carboxamide (CHMFL-PI4K-127) as a novel Plasmodium falciparum PI(4)K inhibitor with potent antimalarial activity against both blood and liver stages of Plasmodium

  摘要：

  Starting from a bipyridine-sulfonamide scaffold, medicinal chemistry optimization leads to the discovery of a novel Plasmodium falciparum PI4K kinase (PfPI4K) inhibitor compound 15g (CHMFL-PI4K-127, IC50: 0.9 nM), which exhibits potent activity against 3D7 Plasmodium falciparum (P. falciparum) (EC50: 25.1 nM). CHMFL-PI4K-127 displays high selectivity against PfPI4K over human lipid and protein kinase. In addition, it exhibits EC50 values of 23-47 nM against a panel of the drug-resistant strains of P. falciparum. In vivo, the inhibitor demonstrates the favorable pharmacokinetic properties in both rats and mice. Furthermore, oral administration of CHMFL-PI4K-127 exhibits the antimalaria efficacy in both blood stage (80 mg/kg) and liver stage (1 mg/kg) of Plasmodium in infected rodent model. The results suggest that CHMFL-PI4K-127 might be a new potential drug candidate for malaria. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.112012

文献信息

• [EN] PYRIDOSULFONAMIDE DERIVATIVES AS PI3 KINASE INHIBITORS<br/>[FR] DÉRIVÉS DE PYRIDOSULFONAMIDE EN TANT QU'INHIBITEURS DE PI3 KINASE
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2009055418A1

  公开（公告）日：2009-04-30

  Invented is a method of inhibiting the activity/function of PB kinases using pyridosulfonamide derivatives. Also invented is a method of treating one or more disease states selected from: autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, allergy, asthma, pancreatitis, multiorgan failure, kidney diseases, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection and lung injuries by the administration of pyridosulfonamide derivatives.

  发明了一种使用吡啶磺酰胺衍生物抑制PB激酶活性/功能的方法。还发明了一种通过给予吡啶磺酰胺衍生物来治疗自身免疫性疾病、炎症性疾病、心血管疾病、神经退行性疾病、过敏、哮喘、胰腺炎、多器官功能衰竭、肾脏疾病、血小板聚集、癌症、精子活动力、移植排斥、移植物排斥和肺部损伤等一种或多种疾病状态的方法。
• PYRIDOSULFONAMIDE DERIVATIVES AS P13 KINASE INHIBITORS
  申请人：Adams Nicholas D.

  公开号：US20100311736A1

  公开（公告）日：2010-12-09

  Invented is a method of inhibiting the activity/function of PI3 kinases using pyridosulfonamide derivatives. Also invented is a method of treating one or more disease states selected from: autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, allergy, asthma, pancreatitis, multiorgan failure, kidney diseases, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection and lung injuries by the administration of pyridosulfonamide derivatives.

  本发明涉及使用吡啶磺酰胺衍生物抑制PI3激酶的活性/功能的方法。本发明还涉及使用吡啶磺酰胺衍生物治疗自身免疫性疾病、炎症性疾病、心血管疾病、神经退行性疾病、过敏、哮喘、胰腺炎、多器官衰竭、肾脏疾病、血小板聚集、癌症、精子运动能力、移植排斥、移植物排斥和肺损伤的方法。
• [EN] NOVEL LIPOSOME KINASE INHIBITOR<br/>[FR] NOUVEL INHIBITEUR DE KINASE LIPOSOME<br/>[ZH] 一种新型的脂质体激酶抑制剂
  申请人：HEFEI INST PHYSICAL SCI CAS

  公开号：WO2020147097A1

  公开（公告）日：2020-07-23

  一种新型的激酶抑制剂，其包括式(I)的化合物或其药学可接受的盐、溶剂化物、酯、酸、代谢物或前药。还提供包括式(I)化合物的药物组合物以及使用这些化合物和组合物用于治疗由PI3K激酶或PfPI4K激酶活化介导的病症，特别是疟疾、癌症和其它的细胞增殖性疾病的用途和方法。
• PYRIDOSULFONAMIDE DERIVATIVES AS PI3 KINASE INHIBITORS
  申请人：GlaxoSmithKline LLC

  公开号：EP2211615A1

  公开（公告）日：2010-08-04
• Discovery of 6′-chloro-N-methyl-5’-(phenylsulfonamido)-[3,3′-bipyridine]-5-carboxamide (CHMFL-PI4K-127) as a novel Plasmodium falciparum PI(4)K inhibitor with potent antimalarial activity against both blood and liver stages of Plasmodium
  作者：Xiaofei Liang、Zongru Jiang、Zhenghui Huang、Feng Li、Cheng Chen、Chen Hu、Wenliang Wang、Zhenquan Hu、Qingwang Liu、Beilei Wang、Li Wang、Ziping Qi、Jing Liu、Lubin Jiang、Qingsong Liu

  DOI：10.1016/j.ejmech.2019.112012

  日期：2020.2

  Starting from a bipyridine-sulfonamide scaffold, medicinal chemistry optimization leads to the discovery of a novel Plasmodium falciparum PI4K kinase (PfPI4K) inhibitor compound 15g (CHMFL-PI4K-127, IC50: 0.9 nM), which exhibits potent activity against 3D7 Plasmodium falciparum (P. falciparum) (EC50: 25.1 nM). CHMFL-PI4K-127 displays high selectivity against PfPI4K over human lipid and protein kinase. In addition, it exhibits EC50 values of 23-47 nM against a panel of the drug-resistant strains of P. falciparum. In vivo, the inhibitor demonstrates the favorable pharmacokinetic properties in both rats and mice. Furthermore, oral administration of CHMFL-PI4K-127 exhibits the antimalaria efficacy in both blood stage (80 mg/kg) and liver stage (1 mg/kg) of Plasmodium in infected rodent model. The results suggest that CHMFL-PI4K-127 might be a new potential drug candidate for malaria. (C) 2019 Elsevier Masson SAS. All rights reserved.