tert-butyl 3-iodo-6-methyl-1H-indazole-1-carboxylate | 1259851-84-7

• 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 3-iodo-6-methyl-1H-indazole-1-carboxylate
• 英文别名: tert-butyl 3-iodo-6-methylindazole-1-carboxylate
• CAS: 1259851-84-7
• 化学式: C₁₃H₁₅IN₂O₂
• 分子量: 358.179
• InChiKey: WGCQNTNGEYZORY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-iodo-6-methyl-1H-indazole-1-carboxylate 在 四(三苯基膦)钯 、 sodium carbonate 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 、 丙酮 为溶剂， 反应 1.0h， 生成 Methyl 2-(6-methyl-3-phenylindazol-1-yl)acetate
  参考文献：
  名称：

  ML212: A small-molecule probe for investigating fluconazole resistance mechanisms in Candida albicans

  摘要：

  国家卫生研究院分子图书馆和探针生产中心网络（NIH-MLPCN）筛选了超过300,000种化合物，以评估它们恢复对耐药念珠菌的氟康唑敏感性的能力。还加入了额外的对照筛选，以去除对哺乳动物或真菌细胞有毒的物质。选择了具有所需生物活性特征的取代吲唑化合物进行进一步开发，并初步研究结构-活性关系导致了ML212的发现。

  DOI：

  10.3762/bjoc.9.171
• 作为产物：
  描述：

  6-甲基吲唑 在 4-二甲氨基吡啶 、 碘 、 potassium carbonate 、 三乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 tert-butyl 3-iodo-6-methyl-1H-indazole-1-carboxylate
  参考文献：
  名称：

  Design, synthesis and structure–activity relationship of indolylindazoles as potent and selective covalent inhibitors of interleukin-2 inducible T-cell kinase (ITK)

  摘要：

  Interleukin-2 inducible T-cell kinase (ITK), a member of the Tec family of tyrosine kinases, plays an important role in T cell signaling downstream of the T-cell receptor (TCR). Herein we report the discovery of a series of indolylindazole based covalent ITK inhibitors with nanomolar inhibitory potency against ITK, good kinase selectivity and potent inhibition of the phosphorylation of PLC gamma l and ERK1/2 in living cells. A computational study provided insight into the interactions between inhibitors and Phe437 at the ATP binding pocket of ITK, suggesting that both edge-to-face pi-pi interaction and the dihedral torsion angle contribute to inhibitors' potency. Compounds 43 and 55 stood out as selective covalent inhibitors with potent cellular activity, which could be used as chemical tools for further study of ITK functions. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111918

文献信息

• Rational Design, Optimization, and Biological Evaluation of Novel MEK4 Inhibitors against Pancreatic Adenocarcinoma
  作者：Ada J. Kwong、Thao N. D. Pham、Hannah E. Oelschlager、Hidayatullah G. Munshi、Karl A. Scheidt

  DOI：10.1021/acsmedchemlett.1c00376

  日期：2021.10.14
• 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.