3-氨基噻吩-4-羧酸甲酯盐酸盐 | 39978-14-8

• 物质功能分类: 医药中间体 - 杂环化合物 - 噻吩类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 中文名称: 3-氨基噻吩-4-羧酸甲酯盐酸盐
• 中文别名: 4-氨基噻吩-3-羧酸甲酯盐酸盐
• 英文名称: methyl 3-amino-4-thiophenecarboxylate hydrochloride
• 英文别名: methyl 4-aminothiophene-3-carboxylate hydrochloride；methyl 3-aminothiophene-4-carboxylate hydrochloride；(4-Methoxycarbonylthiophen-3-yl)azanium;chloride
• CAS: 39978-14-8
• 化学式: C₆H₇NO₂S*ClH
• mdl: MFCD00068149
• 分子量: 193.654
• InChiKey: JGIRDDQLZLXRKQ-UHFFFAOYSA-N

物化性质

• 熔点：
  203-204°C
• 稳定性/保质期：
  常规情况下不会分解，也没有危险的反应。

计算性质

• 辛醇/水分配系数(LogP)：
  1.58
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.166
• 拓扑面积：
  80.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26,S36/37/39
• 危险类别码：
  R36/37/38
• 海关编码：
  2934999090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  密封、阴凉、干燥处保存。

SDS

Name:	Methyl 4-aminothiophene-3-carboxylate hydrochloride 97% Material Safety Data Sheet
Synonym:
CAS:	39978-14-8

Section 1 - Chemical Product MSDS Name:Methyl 4-aminothiophene-3-carboxylate hydrochloride 97% Material Safety Data Sheet
Synonym:

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
39978-14-8	Methyl 4-aminothiophene-3-carboxylate	97%	unlisted

Hazard Symbols: None Listed.
Risk Phrases: None Listed.

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Not available.
Potential Health Effects
Eye:
May cause eye irritation.
Skin:
May cause skin irritation. May be harmful if absorbed through the skin.
Ingestion:
May cause irritation of the digestive tract. May be harmful if swallowed.
Inhalation:
May cause 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.
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.

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Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION
Engineering Controls:
Use adequate ventilation to keep airborne concentrations low.
Exposure Limits CAS# 39978-14-8: 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: brown
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 203 - 204 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: C6H8ClNO2S
Molecular Weight: 194

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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, chlorine, nitrogen oxides, carbon monoxide, oxides of sulfur, carbon dioxide.
Hazardous Polymerization: Has not been reported

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 39978-14-8 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
Methyl 4-aminothiophene-3-carboxylate hydrochloride - 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: Not available.
Risk Phrases:
Safety Phrases:
S 24/25 Avoid contact with skin and eyes.
WGK (Water Danger/Protection)
CAS# 39978-14-8: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 39978-14-8 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 39978-14-8 is not listed on the TSCA inventory.
It is for research and development use only.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

应用

3-氨基噻吩-4-羧酸甲酯盐酸盐是一种医药中间体，可以通过丙烯酸甲酯和巯基乙酸甲酯为原料，经过三步反应制备得到。有文献报道它可用于制备用于治疗转移性恶性黑色素瘤及其他癌症的化合物。

制备 步骤 a：甲基3[(甲氧羰基)甲硫基]丙酸酯

在室温下，将丙烯酸甲酯（4.25g，49.5mmol）滴加到巯基乙酸甲酯（5g，47.16mmol）和哌啶（0.10mL）的溶液中。整个滴加过程超过20分钟。大约一半的丙烯酸酯转化后，再加入一次哌啶（0.10mL）。然后在室温下继续搅拌反应混合物1小时。所得混合物用100mL氯仿稀释，并用水和盐水洗涤以去除氯仿层，随后使用硫酸钠干燥。过滤溶液并蒸发溶剂，得到一种油状产物（9g，收率100%）。

步骤 b：甲基4-氧-2,3,5-三羟基噻吩-3-羧酸酯

在室温下，向干THF中加入甲醇钠（1.68g，31.25mmol），然后在持续搅拌下滴加去甲基-3-硫己烷标准品（5g，26.03mmol）的THF溶液。反应混合物加热回流2小时后冷却至室温，并加入冰冷水以酸化。所得溶液用氯仿萃取并用水和盐水洗涤，再使用硫酸钠干燥。过滤溶液并蒸发溶剂。残留物经过硅胶柱层析（己烷-乙酸乙酯 95:5），获得一种淡黄色油状产物（1.6g，收率39%）。

步骤 c：3-氨基噻吩-4-羧酸甲酯盐酸盐

将4-氧-3-甲氧基羰基四水噻吩（6.5g，40.62mmol）、盐酸羟胺（2.84g，40.62mmol）和乙腈（30mL）混合后回流1小时。冷却反应混合物并过滤分离出固体产物，用干乙醚洗涤后获得3-氨基噻吩-4-羧酸甲酯盐酸盐（4.9g，收率62%），熔点为192-196℃。

反应信息

• 作为反应物：
  描述：

  3-氨基噻吩-4-羧酸甲酯盐酸盐 在 氨 作用下， 以 水 为溶剂， 以65%的产率得到4-氨基噻吩-3-羧酸甲酯
  参考文献：
  名称：

  ANTI-CANCER DRUGS AND USES RELATING THERETO FOR METASTATIC MALIGNANT MELANOMA AND OTHER CANCERS

  摘要：

  本发明公开了一般式(I)和式(II)的三氮烯类似物，其互变异构体、立体异构体、多晶形态、水合物、溶剂合物及其在转移性恶性黑色素瘤和其他癌症，包括但不限于淋巴瘤、肉瘤、癌瘤和胶质瘤中的药用可接受盐。该发明还公开了制备上述式(I)和式(II)的三氮烯类似物以及其药用可接受组合物的方法。

  公开号：

  US20100068178A1
• 作为产物：
  描述：

  4-氧四氢噻酚-3-羧酸甲酯 在 盐酸 、 盐酸羟胺 、 barium carbonate 作用下， 以 甲醇 、 乙醚 、 水 为溶剂， 反应 36.0h， 生成 3-氨基噻吩-4-羧酸甲酯盐酸盐
  参考文献：
  名称：

  天然产物Evodiamine启发的脚手架多样性：高强度和多靶点抗肿瘤药物的发现

  摘要：

  基于天然产物的药物发现中的一个关键问题是如何将产物转化为具有最佳药理特性的类药物分子。天然产物启发的支架多样性的产生是一种有效但具有挑战性的策略，用于研究更广阔的化学空间并确定有前途的药物线索。将我们的工作扩展到天然产物evodiamine，设计并合成了一个包含11个evodiamine启发的新型支架及其衍生物的多样化文库。它们中的大多数显示出对各种人类癌细胞系的良好至优异的抗肿瘤活性。特别地，3-氯-10-羟基硫代吴茱萸碱（66C）显示出优异的体外和体内抗肿瘤功效，耐受性好，毒性低。抗肿瘤机制和靶标分析研究表明，化合物66c是同类中的第一个三重拓扑异构酶I /拓扑异构酶II /微管蛋白抑制剂。总的来说，这项研究为基于天然产物的药物发现提供了有效的策略。

  DOI：

  10.1021/acs.jmedchem.5b00910

文献信息

• Modified aminoacids, pharmaceuticals containing these compounds and method for their production
  申请人：Dr. Karl Thomae GmbH

  公开号：US06344449B1

  公开（公告）日：2002-02-05

  The present invention relates to modified amino acids of general formula wherein A, Z, X, n, m, R, R2, R3, R4 and R11 are defined as in claims 1 to 5, their tautomers, their diastereomers, their enantiomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, pharmaceutical compositions containing these compounds, the use thereof and processes for preparing them as well as their use for the production and purification of antibodies and as labelled compounds in RIA- and ELISA assays and as diagnostic or analytical aids in neurotransmitter research.

  本发明涉及一般式的改性氨基酸 其中 A、Z、X、n、m、R、R2、R3、R4和R11的定义如权利要求1至5中所述，它们的互变异构体、对映异构体、立体异构体、它们的混合物及其盐，特别是其与无机或有机酸或碱的生理上可接受的盐，含有这些化合物的药物组合物，其用途以及制备它们的过程，以及它们在抗体的生产和纯化中的用途以及在RIA和ELISA测定中作为标记化合物以及在神经递质研究中作为诊断或分析辅助工具的用途。
• Modified amino acids, pharmaceuticals containing these compounds and method for their production
  申请人：——

  公开号：US20010036946A1

  公开（公告）日：2001-11-01

  The present invention relates to modified amino acids of general formula 1 wherein A, Z, X, n, m, R, R 2 , R 3 , R 4 and R 11 are defined as in claims 1 to 5 , their tautomers, their diastereomers, their enantiomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, pharmaceutical compositions containing these compounds, the use thereof and processes for preparing them as well as their use for the production and purification of antibodies and as labelled compounds in RIA- and ELISA assays and as diagnostic or analytical aids in neurotransmitter research.

  本发明涉及一般式1的改良氨基酸，其中A、Z、X、n、m、R、R2、R3、R4和R11如权利要求1至5中所定义，它们的互变异构体、对映异构体、混合物及其盐，特别是其与无机或有机酸或碱的生理上可接受的盐，含有这些化合物的药物组合物，其用途以及用于制备它们的过程，以及它们在抗体的生产和纯化中的用途，以及在RIA和ELISA测定中作为标记化合物以及在神经递质研究中作为诊断或分析辅助工具的用途。
• UDP GLYCOSYLTRANSFERASE INHIBITORS AND METHODS OF USE
  申请人：GENZYME CORPORATION

  公开号：US20200102324A1

  公开（公告）日：2020-04-02

  Described herein is a compound of Formula (I), and pharmaceutically acceptable salts thereof. Also described herein are compositions and the use of such compositions in methods of treating a variety of diseases and conditions, in particular Krabbe's Disease (KD) and Metachromatic leukodystrophy (MLD).

  本文描述了一种化合物，其化学式为（I），以及其药用盐。本文还描述了这些组合物以及在治疗各种疾病和症状的方法中使用这些组合物，特别是克拉贝氏病（KD）和间染色质白质脑病（MLD）。
• Switch-on fluorescent/FRET probes to study human histidine triad nucleotide binding protein 1 (hHint1), a novel target for opioid tolerance and neuropathic pain
  作者：Rachit Shah、Andrew Zhou、Carston R. Wagner

  DOI：10.1039/c7ob02472j

  日期：——

  demonstrate that probe 8 exhibits a switch-on FRET property with an active site tryptophan residue (W123). We show the utility of probes in performing quantitative ligand displacement studies, as well as in selective detection of Hint1 in the cell lysates. These probes should be useful for studying the dynamics of the active site, as well as for the development of fluorescence lifetime based high throughput

  组氨酸三联体核苷酸结合蛋白1（Hint1）已成为重要的突触后蛋白，与多种中枢神经系统疾病（如疼痛，成瘾和精神分裂症）相关。最近，用一种小的核苷抑制剂抑制组氨酸核苷酸结合蛋白1（Hint1）已显示出有望作为治疗神经性疼痛的一种新的治疗策略。在这里，我们描述了第一个合理设计的具有双重荧光和FRET特性的小分子开关探针，以研究Hint1。通过连接子将两个荧光寿命分别为20和25 ns的非天然荧光核苷与吲哚环偶联，即探针7和8。发现这两种探针都是水溶性的，并且通过光致电子转移（PET）在分子内淬灭，导致背景荧光最小。与Hint1孵育后，化合物7和8的荧光强度与对照相比分别提高了40倍和16倍。化合物7和8分别以0.121±0.02和2.2±0.36μM的解离常数结合Hint1。我们证明了探针8表现出具有活性位点色氨酸残基（W123）的FRET接通特性。我们展示了探针在进行定量配体置换研究以及细胞裂
• Novel thiophene derivatives which are HM74A agonists
  申请人：Dehmlow Henrietta

  公开号：US20070072873A1

  公开（公告）日：2007-03-29

  The invention is concerned with novel substituted thiophene derivatives of formula (I) wherein R 1 to R 8 , X, m and n are as defined in the description and in the claims, as well as physiologically acceptable salts and esters thereof. These compounds are HM74A agonists and can be used as medicaments.

  这项发明涉及公式（I）的新型取代噻吩衍生物，其中R1至R8、X、m和n的定义如描述和权利要求中所述，以及其生理上可接受的盐和酯。这些化合物是HM74A激动剂，可用作药物。