4-fluoro-2-methyl-6-(4-morpholinyl)-1-(1-naphthalenylmethyl)-1H-benzimidazole | 1372539-98-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 4-fluoro-2-methyl-6-(4-morpholinyl)-1-(1-naphthalenylmethyl)-1H-benzimidazole
• 英文别名: US10660898, Example 15；4-[7-fluoro-2-methyl-3-(naphthalen-1-ylmethyl)benzimidazol-5-yl]morpholine
• CAS: 1372539-98-4
• 化学式: C₂₃H₂₂FN₃O
• 分子量: 375.446
• InChiKey: GDRAKNDUKWAGIF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  30.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-溴-3-硝基-1,2-苯二胺 在 tris-(dibenzylideneacetone)dipalladium(0) 、 2-二环己基磷-2,4,6-三异丙基联苯 pyridine hydrofluoride 、 水 、 铁粉 、 potassium carbonate 、 caesium carbonate 、 iron(II) sulfate 、 sodium nitrite 作用下， 以 1,4-二氧六环 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.5h， 生成 4-fluoro-2-methyl-6-(4-morpholinyl)-1-(1-naphthalenylmethyl)-1H-benzimidazole
  参考文献：
  名称：

  BENZIMIDAZOLE DERIVATIVES AS PI3 KINASE INHIBITORS

  摘要：

  这项发明涉及苯并咪唑衍生物在调节磷脂酰肌醇3′ OH激酶家族（以下简称PI3激酶）的活性或功能，特别是抑制其活性或功能方面的用途。适当地，本发明涉及苯并咪唑在治疗以下一种或多种疾病状态中的用途：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。更适当地，本发明涉及选择性作用于PI3Kβ的苯并咪唑化合物用于治疗癌症。

  公开号：

  US20120088767A1

文献信息

• Benzimidazole Derivatives As PI3 Kinase Inhibitors
  申请人：GlaxoSmithKline LLC

  公开号：US20140378456A1

  公开（公告）日：2014-12-25

  This invention relates to the use of benzimidazole derivatives for the modulation, notably the inhibition of the activity or function of the phosphoinositide 3′ OH kinase family (hereinafter PI3 kinases), suitably, PI3Kα, PI3Kδ, PI3Kβ, and/or PI3Kγ. Suitably, the present invention relates to the use of benzimidazoles in the treatment of 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. More suitably, the present invention relates to PI3Kβ selective benzimidazoles compounds for treating cancer.

  本发明涉及苯并咪唑衍生物的使用，用于调节磷脂酰肌醇3′ OH激酶家族（以下简称PI3激酶）的活性或功能，特别是抑制其活性或功能，适当地，PI3Kα、PI3Kδ、PI3Kβ和/或PI3Kγ。适当地，本发明涉及苯并咪唑在治疗以下一种或多种疾病状态中的使用：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、移植物排斥和肺部损伤。更适当地，本发明涉及PI3Kβ选择性苯并咪唑化合物用于治疗癌症。
• [EN] BENZIMIDAZOLE DERIVATIVES AS PI3 KINASE INHIBITORS<br/>[FR] DÉRIVÉS DE BENZIMIDAZOLE UTILISÉS COMME INHIBITEURS DE PI3 KINASE
  申请人：GLAXOSMITHKLINE LLC

  公开号：WO2012047538A1

  公开（公告）日：2012-04-12

  This invention relates to the use of benzimidazole derivatives for the modulation, notably the inhibition of the activity or function of the phosphoinositide 3' OH kinase family (hereinafter PI3 kinases), suitably, PI3Kα, PI3Kδ, PI3Kβ, and/or PI3Kγ. Suitably, the present invention relates to the use of benzimidazoles in the treatment of 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. More suitably, the present invention relates to PI3Kβ selective benzimidazoles compounds for treating cancer.

  本发明涉及苯并咪唑衍生物在调节磷脂酰肌醇3' OH激酶家族（以下简称PI3激酶），特别是抑制其活性或功能方面的应用，适当地，是PI3Kα、PI3Kδ、PI3Kβ和/或PI3Kγ。适当地，本发明涉及在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、移植物排斥和肺部损伤等一种或多种疾病状态中的苯并咪唑的应用。更适当地，本发明涉及PI3Kβ选择性苯并咪唑化合物用于治疗癌症。
• Benzimidazole derivatives as PI3 kinase inhibitors
  申请人：GLAXOSMITHKLINE LLC

  公开号：US10314845B2

  公开（公告）日：2019-06-11

  This invention relates to the use of benzimidazole derivatives for the modulation, notably the inhibition of the activity or function of the phosphoinositide 3′ OH kinase family (hereinafter PI3 kinases), suitably, PI3Kα, PI3Kδ, PI3Kβ, and/or PI3Kγ. Suitably, the present invention relates to the use of benzimidazoles in the treatment of 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. More suitably, the present invention relates to PI3Kβ selective benzimidazoles compounds for treating cancer.

  本发明涉及苯并咪唑衍生物用于调节，特别是抑制磷酸肌醇 3′ OH 激酶家族（以下简称 PI3 激酶），尤其是 PI3Kα、PI3Kδ、PI3Kβ 和/或 PI3Kγ 的活性或功能。适当地，本发明涉及苯并咪唑在治疗一种或多种疾病状态中的用途，这些疾病状态选自：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、精子活力、移植排斥、移植物排斥和肺损伤。更合适的是，本发明涉及用于治疗癌症的 PI3Kβ 选择性苯并咪唑类化合物。
• Benzimidazole Derivatives as PI3 Kinase Inhibitors
  申请人：GLAXOSMITHKLINE LLC

  公开号：US20180263994A1

  公开（公告）日：2018-09-20

  This invention relates to the use of benzimidazole derivatives for the modulation, notably the inhibition of the activity or function of the phosphoinositide 3′ OH kinase family (hereinafter PI3 kinases), suitably, PI3Kα, PI3Kδ, PI3Kβ, and/or PI3Kγ. Suitably, the present invention relates to the use of benzimidazoles in the treatment of 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. More suitably, the present invention relates to PI3Kβ selective benzimidazoles compounds for treating cancer.
• US8435988B2
  申请人：——

  公开号：US8435988B2

  公开（公告）日：2013-05-07