tert-butyl 6-fluoro-3-iodo-1H-indazole-1-carboxylate | 944904-46-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: tert-butyl 6-fluoro-3-iodo-1H-indazole-1-carboxylate
• 英文别名: tert-butyl 6-fluoro-3-iodoindazole-1-carboxylate
• CAS: 944904-46-5
• 化学式: C₁₂H₁₂FIN₂O₂
• 分子量: 362.142
• InChiKey: OZDYRULATLBCAP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 6-fluoro-3-iodo-1H-indazole-1-carboxylate 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 palladium on activated charcoal 、 水 、 氢气 、 sodium carbonate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 为溶剂， 120.0 ℃ 、101.33 kPa 条件下， 反应 1.25h， 生成 N-(2-(6-fluoro-1H-indazol-3-yl)phenyl)acrylamide
  参考文献：
  名称：

  Rational Design, Optimization, and Biological Evaluation of Novel MEK4 Inhibitors against Pancreatic Adenocarcinoma

  摘要：

  DOI：

  10.1021/acsmedchemlett.1c00376
• 作为产物：
  描述：

  6-氟(1H)吲唑 在 4-二甲氨基吡啶 、 碘 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 40.0h， 生成 tert-butyl 6-fluoro-3-iodo-1H-indazole-1-carboxylate
  参考文献：
  名称：

  3-芳基吲唑类化合物作为选择性MEK4抑制剂的合成与生物学评估。

  摘要：

  在这里，我们报告发现了一系列新型的高效和选择性促分裂原活化蛋白激酶激酶4（MEK4）抑制剂。MEK4是MAPK信号通路中的上游激酶，可响应促有丝分裂和细胞应激反应而使p38 MAPK和JNK磷酸化。MEK4过度表达，并在晚期前列腺癌病变中诱导转移。然而，由于尚未开发出靶向MEK4的选择性化学探针，因此MEK4作为肿瘤靶标的价值尚未得到药理学验证。通过结构-活性关系和分子建模对该系列的优化导致鉴定了化合物6 ff（4-（6-氟-2H-吲唑-3-基）苯甲酸），这是一种高效且选择性的MEK4抑制剂。

  DOI：

  10.1002/cmdc.201900019

文献信息

• 3-ARYLINDAZOLES AS SELECTIVE MEK4 INHIBITORS
  申请人：NORTHWESTERN UNIVERSITY

  公开号：US20200399241A1

  公开（公告）日：2020-12-24

  Disclosed are indazole compounds and derivatives thereof for use as modulators of the activity of mitogen-activated protein kinase 4 (MEK4). The disclosed compounds include 3-Arylindazoles which may be formulated in pharmaceutical composition for treating cell proliferative diseases and disorders associated with MEK4 activity, including cancer.

  本发明涉及用作有丝分裂原活化蛋白激酶4 (MEK4) 活性调节剂的吲唑化合物及其衍生物。所披露的化合物包括3-芳基吲唑，可以制成药物组合物，用于治疗与MEK4活性相关的细胞增殖性疾病和紊乱，包括癌症。
• 3-arylindazoles as selective MEK4 inhibitors
  申请人：NORTHWESTERN UNIVERSITY

  公开号：US11370770B2

  公开（公告）日：2022-06-28

  Disclosed are indazole compounds and derivatives thereof for use as modulators of the activity of mitogen-activated protein kinase 4 (MEK4). The disclosed compounds include 3-Arylindazoles which may be formulated in pharmaceutical composition for treating cell proliferative diseases and disorders associated with MEK4 activity, including cancer.

  本发明公开了用作丝裂原活化蛋白激酶 4（MEK4）活性调节剂的吲唑化合物及其衍生物。所公开的化合物包括3-芳基吲唑，可配制成药物组合物，用于治疗与MEK4活性相关的细胞增殖性疾病和紊乱，包括癌症。
• Identification of potent ITK inhibitors through focused compound library design including structural information
  作者：Matthias Herdemann、Isabelle Heit、Frank-Uwe Bosch、Gianluca Quintini、Claudia Scheipers、Alexander Weber

  DOI：10.1016/j.bmcl.2010.09.119

  日期：2010.12

  A series of novel compound libraries inhibiting interleukin-2 inducible T cell kinase (ITK) were designed, synthesized and evaluated. In the first design cycle two library scaffolds were identified showing low micromolar inhibition of ITK. Further iterative design cycles including crystal structure information of ITK and structurally related kinases led to the identification of indolylindazole and indolylpyrazolopyridine compounds with low nanomolar ITK inhibition. (C) 2010 Elsevier Ltd. All rights reserved.
• RATIONAL DESIGN, OPTIMIZATION, AND BIOLOGICAL EVALUATION OF NOVEL MEK4 INHIBITORS AGAINST PANCREATIC ADENOCARCINOMA
  申请人：NORTHWESTERN UNIVERSITY

  公开号：US20240116875A1

  公开（公告）日：2024-04-11

  Disclosed are indazole compounds and derivatives thereof for use as modulators of the activity of mitogen-activated protein kinase 4 (MEK4). The disclosed compounds include 3-arylindazoles and 3-amino-indazoles which may be formulated in pharmaceutical composition for treating cell proliferative diseases and disorders associated with MEK4 activity, including cancer.