5-(2-(4-(2-(二甲基氨基)乙氧基)苯基)-5-(吡啶-4-基)-1H-咪唑-4-基)-2,3-二氢-1H-茚-1-酮 | 405554-54-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 5-(2-(4-(2-(二甲基氨基)乙氧基)苯基)-5-(吡啶-4-基)-1H-咪唑-4-基)-2,3-二氢-1H-茚-1-酮
• 英文名称: {2-[4-[4-(5-indanyl-1-one)-5-(pyridin-4-yl)-1H-imidazol-2-yl]-phenoxy]-ethyl}-dimethylamine
• 英文别名: 5-{2-[4(2-Dimethylamino-ethoxy)-phenyl]-5-pyridin-4-yl-1H-imidazol-4-yl}-1-indanone；5-(2-(4-(2-(Dimethylamino)ethoxy)phenyl)-5-(pyridin-4-yl)-1H-imidazol-4-yl)-2,3-dihydro-1H-inden-1-one；5-[2-[4-[2-(dimethylamino)ethoxy]phenyl]-5-pyridin-4-yl-1H-imidazol-4-yl]-2,3-dihydroinden-1-one
• CAS: 405554-54-3
• 化学式: C₂₇H₂₆N₄O₂
• 分子量: 438.529
• InChiKey: ZDPSJASIRJASEV-UHFFFAOYSA-N

物化性质

• 沸点：
  665.6±55.0 °C(Predicted)
• 密度：
  1.230±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  71.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(2-(4-(2-(二甲基氨基)乙氧基)苯基)-5-(吡啶-4-基)-1H-咪唑-4-基)-2,3-二氢-1H-茚-1-酮 在 盐酸 、 亚硝酸特丁酯 、 一水合肼 、 potassium hydroxide 作用下， 以 甲乙醚 、 水 、 乙二醇 为溶剂， 反应 2.0h， 以1.9 mg的产率得到(2-{4-[5-(3,8-dihydroindeno[1,2-d] [1,2,3]triazol-6-yl)-4-(pyridin-4-yl)-1H-imidazol-2-yl]-phenoxy}-ethyl)-dimethylamine
  参考文献：
  名称：

  Novel tricyclic pyrazole BRAF inhibitors with imidazole or furan central scaffolds

  摘要：

  V-RAF murine sarcoma viral oncogene homolog B1 (BRAF) is a serine/threonine-specific protein kinase that is mutated with high frequency in cutaneous melanoma, and many other cancers. Inhibition of mutant BRAF is an attractive therapeutic approach for the treatment of melanoma. A triarylimidazole BRAF inhibitor bearing a phenylpyrazole group (dimethyl-[2-(4-{5-[4-(1H-pyrazol-3-yl)-phenyl]-4-pyridin- 4-yl-1H-imidazol-2-yl}-phenoxy)-ethyl]-amine, 1a) was identified as an active BRAF inhibitor. Based on this starting point, we synthesized a series of analogues leading to the discovery of 6-{2-[4-(4-methylpiperazin- 1-yl)-phenyl]-5-pyridin-4-yl-3H-imidazol-4-yl}-2,4-dihydro-indeno[1,2-c]pyrazole (1j), with nanomolar activity in three assays: inhibition of purified mutant BRAF activity in vitro; inhibition of oncogenic BRAF-driven extracellular regulated kinase (ERK) activation in BRAF mutant melanoma cell lines; and inhibition of proliferation in these cells. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.06.031
• 作为产物：
  描述：

  5-{2-[4-(2-dimethylaminoethoxy)-phenyl]-5-(pyridin-4-yl)-1H-imidazol-4-yl}-indan-1-one O-methyloxime 在 盐酸 、 水 作用下， 以 1,4-二氧六环 为溶剂， 以23%的产率得到5-(2-(4-(2-(二甲基氨基)乙氧基)苯基)-5-(吡啶-4-基)-1H-咪唑-4-基)-2,3-二氢-1H-茚-1-酮
  参考文献：
  名称：

  Novel tricyclic pyrazole BRAF inhibitors with imidazole or furan central scaffolds

  摘要：

  V-RAF murine sarcoma viral oncogene homolog B1 (BRAF) is a serine/threonine-specific protein kinase that is mutated with high frequency in cutaneous melanoma, and many other cancers. Inhibition of mutant BRAF is an attractive therapeutic approach for the treatment of melanoma. A triarylimidazole BRAF inhibitor bearing a phenylpyrazole group (dimethyl-[2-(4-{5-[4-(1H-pyrazol-3-yl)-phenyl]-4-pyridin- 4-yl-1H-imidazol-2-yl}-phenoxy)-ethyl]-amine, 1a) was identified as an active BRAF inhibitor. Based on this starting point, we synthesized a series of analogues leading to the discovery of 6-{2-[4-(4-methylpiperazin- 1-yl)-phenyl]-5-pyridin-4-yl-3H-imidazol-4-yl}-2,4-dihydro-indeno[1,2-c]pyrazole (1j), with nanomolar activity in three assays: inhibition of purified mutant BRAF activity in vitro; inhibition of oncogenic BRAF-driven extracellular regulated kinase (ERK) activation in BRAF mutant melanoma cell lines; and inhibition of proliferation in these cells. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.06.031

文献信息

• Imidazole derivatives as raf kinase inhibitors
  申请人：——

  公开号：US20040038964A1

  公开（公告）日：2004-02-26

  Novel compounds (I) and their use as pharmaceuticals particularly as Raf kinase inhibitors for the treatment of neurotraumatic diseases, cancer, chronic neurodegeneration, pain, migraine and cardiac hypertrophy wherein Ar is a group of formula a) or b).

  小说化合物（I）及其作为药物的用途，特别是作为Raf激酶抑制剂用于治疗神经创伤性疾病，癌症，慢性神经退行性疾病，疼痛，偏头痛和心脏肥大，其中Ar是a）或b）公式的一组。
• Cancer treatment method comprising administering an erb-family inhibitor and a raf and/or ras inhibitor
  申请人：Spector Lee Neil

  公开号：US20050176740A1

  公开（公告）日：2005-08-11

  The present invention relates to a method of treating cancer in a mammal and to pharmaceutical combinations useful in such treatment. In particular, the method relates to a cancer treatment method that includes administering an erb family inhibitor and a Raf and/or ras inhibitor to a mammal suffering from a cancer.

  本发明涉及一种治疗哺乳动物癌症的方法和在这种治疗中有用的药物组合。具体来说，该方法涉及一种癌症治疗方法，包括向患有癌症的哺乳动物施用erb家族抑制剂和Raf和/或ras抑制剂。
• IMIDAZOLE DERIVATIVES AS RAF KINASE INHIBITORS
  申请人：DEAN Kenneth David

  公开号：US20070135433A1

  公开（公告）日：2007-06-14

  Novel compounds and their use as pharmaceuticals particularly as Raf kinase inhibitors for the treatment of neurotraumatic diseases, cancer, chronic neurodegeneration, pain, migraine and cardiac hypertrophy.

  小说化合物及其作为药物的使用，特别是作为Raf激酶抑制剂，用于治疗神经创伤性疾病、癌症、慢性神经退化、疼痛、偏头痛和心脏肥大。
• CANCER TREATMENT METHOD COMPRISING ADMINISTRATION OF AN ERB-FAMILY INHIBITOR AND A RAF AND/OR RAS INHIBITOR
  申请人：SmithKline Beecham Corporation

  公开号：EP1492568A1

  公开（公告）日：2005-01-05
• COMPOSITIONS AND METHODS FOR T CELL ENGINEERING
  申请人：Gracell Biotechnologies (Shanghai) Co., Ltd.

  公开号：US20210332101A1

  公开（公告）日：2021-10-28

  The present disclosure relates to an engineered immune cell and use thereof. The present disclosure provides an engineered immune cell comprising a CAR or engineered TCR, which CAR or engineered TCR can comprise a first antigen binding domain and a second antigen binding domain. The engineered immune cells of the present disclosure, when administered into a subject, can inhibit the host immune cells such as T cells and/or NK cells and enhance the survival and persistence of the engineered immune cells in vivo, thereby exhibiting more effective tumor killing activity.