4,6-二氯-3-甲酰基-1H-吲哚-2-甲酸乙酯 | 153435-96-2

• 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: 4,6-二氯-3-甲酰基-1H-吲哚-2-甲酸乙酯
• 中文别名: 4,6-二氯-3-甲酰基-1H-吲哚-2-羧酸乙酯
• 英文名称: ethyl 4,6-dichloro-3-formyl-1H-indole-2-carboxylate
• 英文别名: ethyl-3-formyl-4,6-dichloro-indole-2-carboxylate
• CAS: 153435-96-2
• 化学式: C₁₂H₉Cl₂NO₃
• 分子量: 286.114
• InChiKey: NFILHPVBZNKVNP-UHFFFAOYSA-N

物化性质

• 熔点：
  213 °C

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  59.2
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险品标志：
  Xi
• 危险类别码：
  R36/37/38
• 海关编码：
  2933990090
• 安全说明：
  S26,S37/39
• 储存条件：
  应存于室温、避光且处于惰性气氛中保存。

SDS

Name:	Ethyl 4,6-dichloro-3-formyl-1h-indole-2-carboxylate, 97% Material Safety Data Sheet
Synonym:
CAS:	153435-96-2

Section 1 - Chemical Product MSDS Name: Ethyl 4,6-dichloro-3-formyl-1h-indole-2-carboxylate, 97% Material Safety Data Sheet
Synonym:

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SECTION 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
153435-96-2	Ethyl 4,6-dichloro-3-formyl-1H-indole-	97%	unlisted

Hazard Symbols: XI
Risk Phrases: 36/37/38

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SECTION 3 - HAZARDS IDENTIFICATION EMERGENCY OVERVIEW Irritating to eyes, respiratory system and skin. Potential Health Effects
Eye:
Causes eye irritation.
Skin:
Causes skin irritation. May be harmful if absorbed through the skin.
Ingestion:
May cause irritation of the digestive tract. May be harmful if swallowed.
Inhalation:
Causes respiratory tract irritation. May be harmful if inhaled.
Chronic:
Not available.

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SECTION 4 - FIRST AID MEASURES
Eyes:
Flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid.
Skin:
Get medical aid. Flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes.
Ingestion:
Get medical aid. Wash mouth out with water.
Inhalation:
Remove from exposure and move to fresh air immediately. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medical aid.
Notes to Physician:
Treat symptomatically and supportively.

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SECTION 5 - FIRE FIGHTING MEASURES
General Information:
As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear.
Extinguishing Media:
Use water spray, dry chemical, carbon dioxide, or chemical foam.

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SECTION 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Vacuum or sweep up material and place into a suitable disposal container.

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SECTION 7 - HANDLING and STORAGE
Handling:
Avoid breathing dust, vapor, mist, or gas. Avoid contact with skin and eyes.
Storage:
Store in a cool, dry place. Store in a tightly closed container. Store under an inert atmosphere.

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SECTION 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION
Engineering Controls:
Facilities storing or utilizing this material should be equipped with an eyewash facility and a safety shower. Use adequate ventilation to keep airborne concentrations low. Exposure Limits CAS# 153435-96-2: Personal Protective Equipment
Eyes:
Not available.
Skin:
Wear appropriate protective gloves to prevent skin exposure.
Clothing:
Wear appropriate protective clothing to prevent skin exposure.
Respirators:
Follow the OSHA respirator regulations found in 29 CFR 1910.134 or European Standard EN 149. Use a NIOSH/MSHA or European Standard EN 149 approved respirator if exposure limits are exceeded or if irritation or other symptoms are experienced.

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SECTION 9 - PHYSICAL AND CHEMICAL PROPERTIES
Physical State: Solid
Color: Not available.
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 214 - 217 deg C
Autoignition Temperature: Not available.
Flash Point: Not available.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water:
Specific Gravity/Density:
Molecular Formula: C12H9Cl2NO3
Molecular Weight: 286

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SECTION 10 - STABILITY AND REACTIVITY
Chemical Stability:
Not available.
Conditions to Avoid:
Incompatible materials.
Incompatibilities with Other Materials:
Strong oxidizing agents.
Hazardous Decomposition Products:
Hydrogen chloride, nitrogen oxides, carbon monoxide, carbon dioxide, acrid smoke and fumes.
Hazardous Polymerization: Not available.

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SECTION 11 - TOXICOLOGICAL INFORMATION RTECS#: CAS# 153435-96-2 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
Ethyl 4,6-dichloro-3-formyl-1H-indole-2-carboxylate - Not listed by ACGIH, IARC, or NTP.

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SECTION 12 - ECOLOGICAL INFORMATION

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SECTION 13 - DISPOSAL CONSIDERATIONS Dispose of in a manner consistent with federal, state, and local regulations.

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SECTION 14 - TRANSPORT INFORMATION IATA No information available. IMO No information available. RID/ADR No information available.

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SECTION 15 - REGULATORY INFORMATION European/International Regulations European Labeling in Accordance with EC Directives
Hazard Symbols: XI
Risk Phrases:
R 36/37/38 Irritating to eyes, respiratory system and skin.
Safety Phrases:
S 26 In case of contact with eyes, rinse immediately with plenty of water and seek medical advice. S 37/39 Wear suitable gloves and eye/face protection. WGK (Water Danger/Protection) CAS# 153435-96-2: No information available. Canada None of the chemicals in this product are listed on the DSL/NDSL list. CAS# 153435-96-2 is not listed on Canada's Ingredient Disclosure List. US FEDERAL TSCA CAS# 153435-96-2 is not listed on the TSCA inventory. It is for research and development use only.

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SECTION 16 - ADDITIONAL INFORMATION
MSDS Creation Date: 6/10/2003 Revision #0 Date: Original. The information above is believed to be accurate and represents the best information currently available to us. However, we make no warranty of merchantability or any other warranty, express or implied, with respect to such information, and we assume no liability resulting from its use. Users should make their own investigations to determine the suitability of the information for their particular purposes. In no way shall the company be liable for any claims, losses, or damages of any third party or for lost profits or any special, indirect, incidental, consequential or exemplary damages, howsoever arising, even if the company has been advised of the possibility of such damages.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  4,6-二氯-3-甲酰基-1H-吲哚-2-甲酸乙酯 在 甲酸 、 三苯基膦 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙腈 为溶剂， 反应 13.5h， 生成 3-<2-(noradamantyl-3-aminocarbonyl)ethenyl>-4,6-dichloroindole-2-carboxylic acid ethyl ester
  参考文献：
  名称：

  Cycloalkyl Indole-2-Carboxylates as Useful Tools for Mapping the "North-Eastern" Region of the Glycine Binding Site Associated with the NMDA Receptor

  摘要：

  A novel series of indole-2-carboxylate analogues of GV 150526 (1) in-which the terminal phenyl ring belonging to the side chain present in the position C-3 has been replaced with a bridged cycloalkyl group was synthesized and evaluated for its pharmacological profile. Modelling studies on this class of novel glycine antagonist allowed us to identify an asymmetric lipophilic pocket present in the "North-Eastern" region of the pharmacophoric model of the glycine binding site associated to the NMDA receptor. Among the derivatives prepared, 3-[2-(1-adamantylaminocarbonyl)ethenyl]-4,6-dichloroindole-2-carboxylic acid 6b and 3-[2(norbornylaminocarbonyl)ethenyl]-4,6-dichloroindole-2-carboxylic acid 61 were found to be antagonists acting at the strychnine-insensitive glycine binding site, showing nanomolar affinity for the glycine binding site (K-i = 63 and 19 nM, respectively), coupled with high glutamate receptor selectivity (IC50 > 10(-5) M at the NMDA, AMPA, KA binding sites) and high in vivo potency after :systemic administration by inhibition of convulsion induced by NMDA in mice.

  DOI：

  10.1002/(sici)1521-4184(19993)332:3<73::aid-ardp73>3.0.co;2-5
• 作为产物：
  描述：

  (3,5-dichlorophenyl)hydrazine hydrochloride 在 三氯氧磷 作用下， 以 乙醇 、 1,2-二氯乙烷 、 甲苯 为溶剂， 反应 5.0h， 生成 4,6-二氯-3-甲酰基-1H-吲哚-2-甲酸乙酯
  参考文献：
  名称：

  MDL 103371 的化学开发：用于治疗中风的 N-甲基-d-天冬氨酸型甘氨酸受体拮抗剂

  摘要：

  MDL 103371 是一种 N-甲基-d-天冬氨酸 (NMDA) 型甘氨酸受体拮抗剂，可用于治疗中风。对五种不同的合成路线（包括 Stille、Suzuki、烯醇醚、Knoevenagel 和 Mukaiyama 偶联反应）的评估表明，Knoevenagel 方法在制备大量用于评估的原料药方面具有优势。整个过程使用了一些经典化学。Fischer 吲哚环化，然后是 Vilsmeier-Haack 甲酰化和 Knoevenagel 缩合，可以立即进入目标分子的适当碳框架。用于硝基还原的独特氢化催化剂和溶剂系统，然后是腈的两步酸碱水解，得到粗产物。

  DOI：

  10.1021/op000286s

文献信息

• Discovery of 3-Substituted 1<i>H</i>-Indole-2-carboxylic Acid Derivatives as a Novel Class of CysLT₁Selective Antagonists
  作者：Huayan Chen、Hui Yang、Zhilong Wang、Xin Xie、Fajun Nan

  DOI：10.1021/acsmedchemlett.5b00482

  日期：2016.3.10

  The indole derivative, 3-((E)-3-((3-((E)-2-(7-chloroquinolin-2yl)vinyl)phenyl)amino)-3-oxoprop-1-en-1-yl )-7-methoxy-1H-indole-2-carboxylic acid (17k), was identified as a novel and highly potent and selective CysLT1 antagonist with IC50 values of 0.0059 +/- 0.0011 and 15 +/- 4 muM for CysLT1 and CysLT2, respectively.

  吲哚衍生物3-（（E）-3-（（3-（（E）-2-（7-氯喹啉-2基）乙烯基）苯基）氨基）-3-氧代丙-1-烯-1-基） -7-甲氧基-1H-吲哚-2-羧酸（17k）被确定为一种新型且高效的选择性CysLT1拮抗剂，CysLT1和CysLT2的IC50值为0.0059 +/- 0.0011和15 +/- 4μM，分别。
• Synthesis, labelling and evaluation of hydantoin-substituted indole carboxylic acids as potential ligands for positron emission tomography imaging of the glycine binding site of the N-methyl-d-aspartate receptor
  作者：A. Bauman、M. Piel、S. Höhnemann、A. Krauss、M. Jansen、C. Solbach、G. Dannhardt、F. Rösch

  DOI：10.1002/jlcr.1901

  日期：2011.8

  hydroxy moiety to obtain the radiolabelled ligands through an alkylation reaction. Radiosynthesis was achieved by labelling the precursor ethyl 4,6-dichloro-3-((3-(4-hydroxyphenyl)-2,4-dioxoimidazolidin-1-yl)methyl)-indole-2-carboxylate with 2-[18F]fluoroethyl tosylate or [11C]methyl iodide and subsequent cleavage of the ethyl ester moiety. This gave the final products in overall decay-corrected radiochemical

  N-甲基-d-天冬氨酸（NMDA）受体作为一种离子型谷氨酸能受体对于生理过程如学习、记忆和突触可塑性是必不可少的。谷氨酸诱导的这些受体过度激活，伴随着细胞内钙浓度的增加，会导致细胞损伤并导致大量急性或慢性神经系统疾病，如中风、外伤、帕金森病和阿尔茨海默病。为了用正电子发射断层扫描可视化体内谷氨酸能神经传递，合成了基于乙内酰脲取代的吲哚-2-羧酸的先导结构的新型氟乙氧基和甲氧基取代的参考化合物。NMDA 受体对甘氨酸结合位点的亲和力显示 Ki 值介于 322 和 11 nM 之间，亲脂性的 logD 值介于 1.51 到 2.53 之间。在这些结果的基础上，合成了含有酚羟基部分的前体化合物，以通过烷基化反应获得放射性标记的配体。通过用 2-[18F] 标记前体 4,6-二氯-3-((3-(4-羟基苯基)-2,4-dioxoimidazolidin-1-yl)methyl)-indole-2-carboxylate
• Substituted Indole-2-carboxylates as <i>in Vivo</i> Potent Antagonists Acting as the Strychnine-Insensitive Glycine Binding Site
  作者：Romano Di Fabio、Anna M. Capelli、Nadia Conti、Alfredo Cugola、Daniele Donati、Aldo Feriani、Paola Gastaldi、Giovanni Gaviraghi、Cheryl T. Hewkin、Fabrizio Micheli、Andrea Missio、Manolo Mugnaini、Angelo Pecunioso、Anna M. Quaglia、Emiliangelo Ratti、Luciana Rossi、Giovanna Tedesco、David G. Trist、Angelo Reggiani

  DOI：10.1021/jm960644a

  日期：1997.3.1

  strychnine-insensitive glycine binding site (noncompetitive inhibition of the binding of [3H]TCP, pA2 = 8.1) displaying nanomolar affinity for the glycine binding site (pKi = 8.5), coupled with high glutamate receptor selectivity (> 1000-fold relative to the affinity at the NMDA, AMPA, and kainate binding sites). This indole derivative inhibited convulsions induced by NMDA in mice, when administered by both

  合成了一系列在吲哚核的C-3位置带有合适链的吲哚-2-羧酸盐，并使用[3H]甘氨酸结合测定对体外亲和力进行了评估，并通过抑制N-诱导的惊厥来对体内效力进行了评估。小鼠中的D-天冬氨酸甲酯（NMDA）。3- [2-[（（苯基氨基）羰基]乙烯基] -4,6-二氯吲哚-2-羧酸（8）是对苯丙氨酸不敏感的甘氨酸结合位点的拮抗剂（对[3H] TCP的结合进行非竞争性抑制，pA2 = 8.1），显示出对甘氨酸结合位点的纳摩尔亲和力（pKi = 8.5），并具有高谷氨酸受体选择性（相对于NMDA，AMPA和海藻酸酯结合位点的亲和力> 1000倍）。当通过静脉和口服途径给药时（ED50 = 0.06和6 mg / kg，分别）。研究了取代基对C-3侧链的末端苯环的影响。QSAR分析表明，pKi值随亲脂性和取代基的空间体积而降低，并随存在于末端苯环对位的基团的电子供体共振效应而增加。根据这些结果，C-3侧链
• Synthesis of (E)-3-(2-carboxy-2-pyridyl-vinyl)-4,6-dichloro-1H-indole-2-carboxylic acids, glycine-site NMDA receptor antagonists, utilizing the Knoevenagel condensation reaction
  作者：Robert J Cregge、Robert A Farr、Dirk Friedrich、Jos Hulshof、David A Janowick、Scott Meikrantz、William A Metz

  DOI：10.1016/s0040-4039(00)02270-x

  日期：2001.2

  The Knoevenagel condensation of arylacetonitriles with ethyl 4,6-dichloro-3-formyl-1H-indole-2-carboxylate (2), followed by hydrolysis, provides a convenient entry into a series of analogs of MDL 105,519, 1, a selective glycine site N-methyl-d-aspartate (NMDA) receptor antagonist. Surprisingly, the hydrolysis of the indole arylpropenenitriles terminates at the formation of the corresponding carboxamide

  arylacetonitriles的Knoevenagel缩合用乙酸乙酯4,6-二氯-3-甲酰基-1- ħ -吲哚-2-羧酸甲酯（2），接着进行水解，提供了方便的入口成一系列MDL 105519，类似物的1，选择性甘氨酸位点N-甲基-d-天冬氨酸（NMDA）受体拮抗剂。令人惊讶地，吲哚芳基丙烯腈的水解终止于相应羧酰胺的形成，并且没有进一步进行为所需的二羧酸。然而，当芳基取代基是吡啶时，水解通过该系列独特的氮杂环庚烷吲哚进行，其在进一步水解时平稳地转化为所需的二羧酸类似物。
• NMDA (n-methyl-d-aspartate) antagonists
  申请人：Hoechst Marion Roussell, Inc.

  公开号：US05922752A1

  公开（公告）日：1999-07-13

  The present invention is new excitatory amino acid antagonists (herein referred to as compounds of formula (1)): below: ##STR1## These new antagonists are useful as NMDA (N-methyl-D-aspartate) antagonists.

  本发明是新的兴奋性氨基酸拮抗剂（以下简称为式（1）的化合物）：如下：##STR1## 这些新的拮抗剂可用作NMDA（N-甲基-D-天冬氨酸）拮抗剂。