2-氯-1-(5-甲氧基-1H-吲哚-3-基)-乙酮 | 30030-91-2

• 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
• 中文名称: 2-氯-1-(5-甲氧基-1H-吲哚-3-基)-乙酮
• 英文名称: 2-chloro-1-(5-methoxy-1H-indol-3-yl)ethanone
• 英文别名: 5-Methoxy-3-chloracetyl-indol
• CAS: 30030-91-2
• 化学式: C₁₁H₁₀ClNO₂
• mdl: MFCD03289190
• 分子量: 223.659
• InChiKey: QBFUNASXZRQFBJ-UHFFFAOYSA-N

物化性质

• 熔点：
  130 °C
• 沸点：
  413.8±30.0 °C(Predicted)
• 密度：
  1.325±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  42.1
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  2-氯-1-(5-甲氧基-1H-吲哚-3-基)-乙酮 在 palladium on activated charcoal sodium hydroxide 、 sodium azide 、 氢气 、 三乙胺 、 [双(2-甲氧基乙基)胺]三氟化硫 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 1,2-二氯乙烷 、 丙酮 为溶剂， 反应 4.0h， 生成 tert-butyl 3-(2-acetylamino-1,1-difluoro-ethyl)-5-methoxy-indole-1-carboxylate
  参考文献：
  名称：

  Syntheses of β,β-Difluorotryptamines

  摘要：

  Tryptamines disubstituted at the beta-position with fluorine have been synthesized as part of our research program to study the effects of fluorine substitution on the biological activities of neuroactive amines. Treatment of N-Boc-3-azidoacetyl indoles, prepared from readily available 2-chloracetylindoles, with dimethoxyethylamino sulfurtrifluoride produced the corresponding 3-(2-azido-1,1-difluoroethyl)indoles. Reduction of the azide to amine with hydrogen over Pd-C and careful removal of the N-Boc protecting group produced beta,beta-difluorotryptamines.

  DOI：

  10.1021/jo020731c
• 作为产物：
  描述：

  5-甲氧基吲哚 、 氯乙酰氯 在 吡啶 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 生成 2-氯-1-(5-甲氧基-1H-吲哚-3-基)-乙酮
  参考文献：
  名称：

  3-取代-1 H-吲哚衍生物作为NR2B / NMDA受体拮抗剂的开发

  摘要：

  以前基于配体和基于结构的组合方法使我们能够鉴定出含有吲哚支架的NR2B / NMDA受体拮抗剂。为了进一步探索这类衍生物的主要结构活性关系，我们在此报告了新类似物的设计，合成和生物学评估。一些衍生物被证明具有显着的抗惊厥特性和NMDA拮抗作用。其中最活跃的（3d）与ifenprodil的NR2B结合亲和力相等。这些结果也得到了计算研究的证实。

  DOI：

  10.1016/j.bmc.2008.12.058

文献信息

• Development of 3-substituted-1H-indole derivatives as NR2B/NMDA receptor antagonists
  作者：Rosaria Gitto、Laura De Luca、Stefania Ferro、Rita Citraro、Giovambattista De Sarro、Lara Costa、Lucia Ciranna、Alba Chimirri

  DOI：10.1016/j.bmc.2008.12.058

  日期：2009.2

  previously allowed us to identify NR2B/NMDA receptor antagonists containing indole scaffold. In order to further explore the main structure activity relationships of this class of derivatives we herein report the design, synthesis and biological evaluation of new analogues. Some derivatives demonstrated to produce significant anticonvulsant properties and NMDA antagonism. The most active of them (3d)

  以前基于配体和基于结构的组合方法使我们能够鉴定出含有吲哚支架的NR2B / NMDA受体拮抗剂。为了进一步探索这类衍生物的主要结构活性关系，我们在此报告了新类似物的设计，合成和生物学评估。一些衍生物被证明具有显着的抗惊厥特性和NMDA拮抗作用。其中最活跃的（3d）与ifenprodil的NR2B结合亲和力相等。这些结果也得到了计算研究的证实。
• 3-Indolylpiperidine
  申请人：MERCK PATENT GmbH

  公开号：EP0683166A1

  公开（公告）日：1995-11-22

  3-Indolylpiperidine der Formel I worin R¹, R², R³ und R⁴jeweils unabhängig voneinander H, A, OH, OA, F, Cl, Br, I, CN, CF₃, COOH, CONH₂, CONHA, CONA₂ oder COOA, oder R¹ und R² sowie R³ und R⁴ jeweils zusammen auch Methylendioxy, R⁵H oder OH, R⁶H oder R⁵ und R⁶auch gemeinsam eine Bindung, AAlkyl mit 1 bis 6 C-Atomen n2, 3, 4, 5 oder 6 bedeuten, sowie deren physiologisch unbedenkliche Salze zeigen Wirkung auf das Zentralnervensystem, insbesondere Dopamin-agonistische oder Dopamin-antagonistische Wirkung.

  式 I 的 3-吲哚基哌啶类化合物 其中 R¹、R²、R³ 和 R⁴ 各自独立地为 H、A、OH、OA、F、Cl、Br、I、CN、CF₃、COOH、CONH₂、CONHA、CONA₂ 或 COOA，或 R¹ 和 R² 以及 R³ 和 R⁴ 同时也是亚甲基二氧基、 R⁵H 或 OH、 R⁶H或 R⁵和 R⁶也共同形成一个键、 具有 1 至 6 个 C 原子的烷基 n2、3、4、5 或 6 表示、 以及它们对人体无害的盐类对中枢神经系统有影响，特别是多巴胺拮抗作用或多巴胺拮抗作用。
• Synthesis, modelling and biological characterization of 3-substituted-1H-indoles as ligands of GluN2B-containing N-methyl-d-aspartate receptors
  作者：Rosaria Gitto、Laura De Luca、Stefania Ferro、Emilio Russo、Giovambattista De Sarro、Mariangela Chisari、Lucia Ciranna、Julio Alvarez-Builla、Ramon Alajarin、Maria Rosa Buemi、Alba Chimirri

  DOI：10.1016/j.bmc.2013.12.040

  日期：2014.2

  A three-step synthetic pathway has been employed to synthesize a small library of 2-(4-arylpiperidin-1-yl)-1-(1H-indol-3-yl)ethanone and 2-(4-arylpiperidin-1-yl)-1-(1H-indol-3-yl) ethane-1,2-dione derivatives that have been screened in [H-3]ifenprodil competition binding assay. Some compounds exhibited significant binding affinity at nanomolar concentration, the most active being ligand 35 (IC50 = 5.5 nM). Docking experiments suggested the main interactions between 35 and GluN2B-containing NMDA receptors. Notably, the compound 35 reduced NMDA-mediated excitatory post-synaptic currents recorded in mouse hippocampal slices indicating antagonistic effects (50 nM). Moreover, the compound 35 has shown antioxidant effects in a preliminary screening, thus suggesting that it might be considered prototype for future drug development of novel 'dual target' neuroprotective agents. (C) 2013 Elsevier Ltd. All rights reserved.
• Synthesis and Biological Characterization of 3-Substituted-1<i>H</i>-indoles as Ligands of GluN2B-Containing <i>N</i>-Methyl-<scp>d</scp>-aspartate Receptors
  作者：Rosaria Gitto、Laura De Luca、Stefania Ferro、Maria Rosa Buemi、Emilio Russo、Giovambattista De Sarro、Lara Costa、Lucia Ciranna、Orazio Prezzavento、Emanuela Arena、Simone Ronsisvalle、Giuseppe Bruno、Alba Chimirri

  DOI：10.1021/jm2008002

  日期：2011.12.22

  As an extension of our studies, novel indole derivatives were rationally designed and synthesized as ligands targeted to GluN2B/NMDA receptors. The 2-(4-benzylpiperidin-1-yl)-1-(6-hydroxy-1H-indol-3-yl)ethanone (4i) and 1-(4-benzylpiperidin-l-yl)-2-(6-hydroxy-1H-indol-3-yl)ethane-1,2-dione (6i) showed high binding affinity in [H-3]ifenprodil displacement assay. By computational studies, we suggested the hypothetical interactions playing a significant role during the binding process. However, in functional and in vivo studies the most potent compound 4i did not show any activity whereas it displayed relevant affinity toward the sigma(2) receptor.
• Antiulcer agents. 4-Substituted 2-guanidinothiazoles: reversible, competitive, and selective inhibitors of gastric H+,K+-ATPase
  作者：John L. LaMattina、Peter A. McCarthy、Lawrence A. Reiter、William F. Holt、Li An Yeh

  DOI：10.1021/jm00164a012

  日期：1990.2

  A series of 4-substituted 2-guanidinothiazoles has been found to inhibit the gastric proton-pump enzyme H+,K(+)-ATPase. In general, these compounds were reversible inhibitors of canine gastric H+,K(+)-ATPase, competitive at the K+ site, and selective relative to canine renal Na+,K(+)-ATPase. Structure-activity relationship (SAR) studies on this series revealed no general replacement for the guanidinothiazole. On the other hand, use of pyrrolyl, phenyl, and indolyl groups as the C-4 substituent yielded active compounds. Extensive studies of substitution patterns on these 4-aryl groups led to more active compounds, but no consistent SAR became apparent. Monosubstitution of the guanidine and substitution of the thiazole at C-5 both often led to increased activity, but combining these changes generated compounds less active than the parents. Despite 100-fold improvement in in vitro inhibitory potency, only a 3-fold increase in gastric antisecretory activity in rats was observed for these agents.