Tert-butyl 5-ethynylindoline-1-carboxylate | 1073191-24-8

• 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: Tert-butyl 5-ethynylindoline-1-carboxylate
• 英文别名: tert-butyl 5-ethynyl-2,3-dihydroindole-1-carboxylate
• CAS: 1073191-24-8
• 化学式: C₁₅H₁₇NO₂
• 分子量: 243.305
• InChiKey: VUKVJTRSPIJTKC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(2-(2-(4-iodophenoxy)ethoxy)ethoxy)ethan-1-ol 、 Tert-butyl 5-ethynylindoline-1-carboxylate 在 copper(l) iodide 、 四(三苯基膦)钯 、 三乙胺 作用下， 以 乙腈 为溶剂， 反应 1.5h， 生成
  参考文献：
  名称：

  Synthesis and evaluation of indolinyl- and indolylphenylacetylenes as PET imaging agents for β-amyloid plaques

  摘要：

  Two new phenylacetylene derivatives, 5-((4-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)phenyl)ethynyl)indoline 8 and 5-((4-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)phenyl)ethynyl)-1H-indole 14, targeting beta-amyloid ( Ab) plaques have been prepared. In vitro binding carried out in tissue homogenates prepared from postmortem AD brains with [(125)[] IMPY (6-iodo-2-(40-dimethylamino-phenyl-imidazo[1,2-a]pyridine) as the radioligand indicated good binding affinities (K-i = 4.0 and 1.5 nM for 8 and 14, respectively). Brain penetration of the corresponding radiofluorinated ligands, evaluated in the normal mice, showed good initial brain penetration (4.50 and 2.43% ID/g (injected dose/gram) for [F-18]8 and [F-18]14 at 2 min after injection) with moderate to low washout rates from the brain (1.71% ID/g at 2h and 2.10% ID/g at 3 h, respectively). Autoradiography and homogenate binding studies demonstrated the high specific binding of [F-18]14 to the Ab plaques; however, [F-18]8 showed low specific binding. These preliminary results identified that indolylphenylacetylene, 14, may be a good lead for further structural modi. cation to develop a useful Ab plaque imaging agent. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.07.077
• 作为产物：
  描述：

  在 氢氧化钾 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 0.5h， 生成 Tert-butyl 5-ethynylindoline-1-carboxylate
  参考文献：
  名称：

  Synthesis and evaluation of indolinyl- and indolylphenylacetylenes as PET imaging agents for β-amyloid plaques

  摘要：

  Two new phenylacetylene derivatives, 5-((4-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)phenyl)ethynyl)indoline 8 and 5-((4-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)phenyl)ethynyl)-1H-indole 14, targeting beta-amyloid ( Ab) plaques have been prepared. In vitro binding carried out in tissue homogenates prepared from postmortem AD brains with [(125)[] IMPY (6-iodo-2-(40-dimethylamino-phenyl-imidazo[1,2-a]pyridine) as the radioligand indicated good binding affinities (K-i = 4.0 and 1.5 nM for 8 and 14, respectively). Brain penetration of the corresponding radiofluorinated ligands, evaluated in the normal mice, showed good initial brain penetration (4.50 and 2.43% ID/g (injected dose/gram) for [F-18]8 and [F-18]14 at 2 min after injection) with moderate to low washout rates from the brain (1.71% ID/g at 2h and 2.10% ID/g at 3 h, respectively). Autoradiography and homogenate binding studies demonstrated the high specific binding of [F-18]14 to the Ab plaques; however, [F-18]8 showed low specific binding. These preliminary results identified that indolylphenylacetylene, 14, may be a good lead for further structural modi. cation to develop a useful Ab plaque imaging agent. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.07.077

文献信息

• Design and synthesis of potent substrate-based inhibitors of the Trypanosoma cruzi dihydroorotate dehydrogenase
  作者：Daniel Ken Inaoka、Maiko Iida、Satoshi Hashimoto、Toshiyuki Tabuchi、Takefumi Kuranaga、Emmanuel Oluwadare Balogun、Teruki Honma、Akiko Tanaka、Shigeharu Harada、Takeshi Nara、Kiyoshi Kita、Masayuki Inoue

  DOI：10.1016/j.bmc.2017.01.009

  日期：2017.2

  Chagas disease, caused by the parasitic protozoan Trypanosoma cruzi, is the leading cause of heart disease in Latin America. T. cruzi dihydroorotate dehydrogenase (DHODH), which catalyzes the production of orotate, was demonstrated to be essential for T. cruzi survival, and thus has been considered as a potential drug target to combat Chagas disease. Here we report the design and synthesis of 75 compounds based on the orotate structure. A comprehensive structure-activity relationship (SAR) study revealed two 5-substituted orotate analogues (5u and 5v) that exhibit nPP values of several ten nanomolar level and a selectivity of more than 30,000-fold over human DHODH. The information presented here will be invaluable in the search for next-generation drug leads for Chagas disease. (C) 2017 Elsevier Ltd. All rights reserved.
• Synthesis and evaluation of indolinyl- and indolylphenylacetylenes as PET imaging agents for β-amyloid plaques
  作者：Wenchao Qu、Seok-Rye Choi、Catherine Hou、Zhiping Zhuang、Shunichi Oya、Wei Zhang、Mei-Ping Kung、Rajesh Manchandra、Daniel M. Skovronsky、Hank F. Kung

  DOI：10.1016/j.bmcl.2008.07.077

  日期：2008.9

  Two new phenylacetylene derivatives, 5-((4-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)phenyl)ethynyl)indoline 8 and 5-((4-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)phenyl)ethynyl)-1H-indole 14, targeting beta-amyloid ( Ab) plaques have been prepared. In vitro binding carried out in tissue homogenates prepared from postmortem AD brains with [(125)[] IMPY (6-iodo-2-(40-dimethylamino-phenyl-imidazo[1,2-a]pyridine) as the radioligand indicated good binding affinities (K-i = 4.0 and 1.5 nM for 8 and 14, respectively). Brain penetration of the corresponding radiofluorinated ligands, evaluated in the normal mice, showed good initial brain penetration (4.50 and 2.43% ID/g (injected dose/gram) for [F-18]8 and [F-18]14 at 2 min after injection) with moderate to low washout rates from the brain (1.71% ID/g at 2h and 2.10% ID/g at 3 h, respectively). Autoradiography and homogenate binding studies demonstrated the high specific binding of [F-18]14 to the Ab plaques; however, [F-18]8 showed low specific binding. These preliminary results identified that indolylphenylacetylene, 14, may be a good lead for further structural modi. cation to develop a useful Ab plaque imaging agent. (C) 2008 Elsevier Ltd. All rights reserved.