ethyl [6-(4,4-dimethyloxazolin-2-yl)-5-methyl]indole-2-carboxylate | 782499-21-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: ethyl [6-(4,4-dimethyloxazolin-2-yl)-5-methyl]indole-2-carboxylate
• 英文别名: ethyl 6-(4,4-dimethyl-5H-1,3-oxazol-2-yl)-5-methyl-1H-indole-2-carboxylate
• CAS: 782499-21-2
• 化学式: C₁₇H₂₀N₂O₃
• 分子量: 300.357
• InChiKey: LYUWLLCCYWBNLC-UHFFFAOYSA-N

物化性质

• 沸点：
  473.9±45.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  63.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl [6-(4,4-dimethyloxazolin-2-yl)-5-methyl]indole-2-carboxylate 在 manganese(IV) oxide 、 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 14.5h， 生成 [6-(4,4-dimethyloxazolin-2-yl)-5-methyl]indole-2-carboxaldehyde
  参考文献：
  名称：

  Rational design of a nonpeptide general chemical scaffold for reversible inhibition of PDZ domain interactions

  摘要：

  Novel small molecules were designed to specifically target the ligand-binding pocket of a PDZ domain. Iterative molecular docking and modeling allowed the design of an indole scaffold 10a as a reversible inhibitor of ligand binding. The 10a scaffold inhibited the interaction between MAGI-3 and PTEN and showed cellular activities that are consistent with the inhibition of NHERF-1 function. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.10.006
• 作为产物：
  描述：

  2-[(3-amino-4-iodo-6-methyl)phenyl]-4,4-dimethyloxazoline 、 丙酮酸乙酯 在 三乙烯二胺 、 palladium diacetate 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 0.83h， 以44%的产率得到ethyl [6-(4,4-dimethyloxazolin-2-yl)-5-methyl]indole-2-carboxylate
  参考文献：
  名称：

  Small molecule inhibition of a PDZ-domain interaction

  摘要：

  已发现的新型化合物可有效抑制PDZ结构域相互作用，特别是MAGIs中的PDZ结构域与肿瘤抑制蛋白PTEN之间的相互作用，以及Dishevelled（Dvl）蛋白中的PDZ结构域与其他蛋白如Frizzled（Fz）蛋白之间的相互作用，其一般公式如下。该发明还包括用这些化合物进行筛选和研究蛋白的组合库、阵列和方法。该发明的化合物已在过度表达Dishevelled蛋白（Dvl）的某些细胞系中诱导细胞凋亡；抑制Wnt信号传导。

  公开号：

  US20050043385A1

文献信息

• US7601750B2
  申请人：——

  公开号：US7601750B2

  公开（公告）日：2009-10-13
• Small molecule inhibition of a PDZ-domain interaction
  申请人：Guy Kiplin R.

  公开号：US20050043385A1

  公开（公告）日：2005-02-24

  Novel compounds that have been found effective in inhibiting PDZ domain interactions, and particularly interactions of PDZ domains in MAGIs with the oncogenic (tumor suppressor) protein PTEN and interactions between the PDZ domain in the Dishevelled (Dvl) protein and other proteins such as the Frizzled (Fz) protein, have the general formula The invention also includes combinatorial libraries, arrays and methods for screening and studying proteins using such compounds. Compounds of the invention have produced apoptosis in certain cell lines that overexpress the Dishevelled protein (Dvl); inhibiting Wnt signaling.

  已发现的新型化合物可有效抑制PDZ结构域相互作用，特别是MAGIs中的PDZ结构域与肿瘤抑制蛋白PTEN之间的相互作用，以及Dishevelled（Dvl）蛋白中的PDZ结构域与其他蛋白如Frizzled（Fz）蛋白之间的相互作用，其一般公式如下。该发明还包括用这些化合物进行筛选和研究蛋白的组合库、阵列和方法。该发明的化合物已在过度表达Dishevelled蛋白（Dvl）的某些细胞系中诱导细胞凋亡；抑制Wnt信号传导。
• Rational design of a nonpeptide general chemical scaffold for reversible inhibition of PDZ domain interactions
  作者：Naoaki Fujii、Jose J. Haresco、Kathleen A.P. Novak、Robert M. Gage、Nicoletta Pedemonte、David Stokoe、Irwin D. Kuntz、R. Kiplin Guy

  DOI：10.1016/j.bmcl.2006.10.006

  日期：2007.1

  Novel small molecules were designed to specifically target the ligand-binding pocket of a PDZ domain. Iterative molecular docking and modeling allowed the design of an indole scaffold 10a as a reversible inhibitor of ligand binding. The 10a scaffold inhibited the interaction between MAGI-3 and PTEN and showed cellular activities that are consistent with the inhibition of NHERF-1 function. (c) 2006 Elsevier Ltd. All rights reserved.