异喹啉-1-羧酸甲酯 | 27104-72-9

• 物质功能分类: 医药中间体 - 杂环化合物 - 异喹啉类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 中文名称: 异喹啉-1-羧酸甲酯
• 中文别名: 1-异喹啉甲酸甲酯
• 英文名称: methyl isoquinoline-1-carboxylate
• 英文别名: methyl isoquinolinecarboxylate；methyl 1-isoquinolinecarboxylate
• CAS: 27104-72-9
• 化学式: C₁₁H₉NO₂
• 分子量: 187.198
• InChiKey: WJHGJDGITRCZLH-UHFFFAOYSA-N

物化性质

• 密度：
  1.210

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933499090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  室温

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: Methyl isoquinoline-1-carboxylate
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

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Section 3. Composition/information on ingredients.
Ingredient name: Methyl isoquinoline-1-carboxylate
CAS number: 27104-72-9

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Section 4. First aid measures
Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing
contaminated clothing and shoes. If irritation persists, seek medical attention.
Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical
attention.
Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

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Section 5. Fire fighting measures
In the event of a fire involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

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Section 6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution: Wear approved mask/respirator
Hand precaution: Wear suitable gloves/gauntlets
Skin protection: Wear suitable protective clothing
Eye protection: Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

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Section 7. Handling and storage
Handling: This product should be handled only by, or under the close supervision of, those properly qualified
in the handling and use of potentially hazardous chemicals, who should take into account the fire,
health and chemical hazard data given on this sheet.
Store in closed vessels.
Storage:

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Section 8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

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Section 9. Physical and chemical properties
Appearance: Not specified
Boiling point: No data
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C11H9NO2
Molecular weight: 187.2

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Section 10. Stability and reactivity
Conditions to avoid: Heat, flames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide, nitrogen oxides.

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Section 11. Toxicological information
No data.

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Section 12. Ecological information
No data.

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Section 13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

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Section 14. Transportation information
Non-harzardous for air and ground transportation.

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Section 15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  异喹啉-1-羧酸甲酯 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 5.0h， 以54%的产率得到1-异喹啉基甲醇
  参考文献：
  名称：

  [EN] ADENOSINE RECEPTOR BINDING COMPOUNDS
  [FR] COMPOSÉS SE LIANT AU RÉCEPTEUR DE L'ADÉNOSINE

  摘要：

  本发明涉及化学式（I）的药物化合物和组合物，以及使用这些化合物和组合物进行治疗的方法，特别是用于治疗和/或预防增殖性疾病，如癌症。如本文进一步描述的化合物（I）被显示为腺苷A2A受体的调节剂，并表现出抗增殖活性。因此，这些化合物对于治疗增殖性疾病如癌症以及其他与腺苷受体相关的疾病条件包括炎症性疾病、肾脏疾病、糖尿病、血管疾病、肺部疾病或自身免疫疾病是有用的。

  公开号：

  WO2020014332A1
• 作为产物：
  描述：

  methyl 2-(4-methylphenyl)sulfonyl-3,4-dihydro-1H-isoquinoline-1-carboxylate 在 氧气 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 二甲基亚砜 为溶剂， 反应 2.0h， 以93%的产率得到异喹啉-1-羧酸甲酯
  参考文献：
  名称：

  通过串联β-消除和芳构化将N-甲苯磺酰基四氢异喹啉有效且实用地一锅转化为异喹啉以及将N-甲苯磺酰基四氢-β-咔啉转化为β-咔啉

  摘要：

  描述了一种将 N-tosyltetrahydroisoquinolines (N-tosyl-THIQs) 转化为异喹啉和将 N-tosyltetrahydro-β-carbolines (N-tosyl-THBCs) 转化为 β-咔啉的有效、实用和通用的方法。在二甲基亚砜中用碱处理 N-tosyl-THIQs 或 N-tosyl-THBCs 得到作为中间体的二氢异喹啉或二氢-β-咔啉，然后这些被分子氧原位氧化得到异喹啉或 β-咔啉。产量。两种一锅法转化都是通过串联β-消除和芳构化发生的。

  DOI：

  10.1002/ejoc.201001153

文献信息

• Dual-action inhibitors of HIF prolyl hydroxylases that induce binding of a second iron ion
  作者：Kar Kheng Yeoh、Mun Chiang Chan、Armin Thalhammer、Marina Demetriades、Rasheduzzaman Chowdhury、Ya-Min Tian、Ineke Stolze、Luke A. McNeill、Myung Kyu Lee、Esther C. Y. Woon、Mukram M. Mackeen、Akane Kawamura、Peter J. Ratcliffe、Jasmin Mecinović、Christopher J. Schofield

  DOI：10.1039/c2ob26648b

  日期：——

  Inhibition of the hypoxia-inducible factor (HIF) prolyl hydroxylases (PHD or EGLN enzymes) is of interest for the treatment of anemia and ischemia-related diseases. Most PHD inhibitors work by binding to the single ferrous ion and competing with 2-oxoglutarate (2OG) co-substrate for binding at the PHD active site. Non-specific iron chelators also inhibit the PHDs, both in vitro and in cells. We report the identification of dual action PHD inhibitors, which bind to the active site iron and also induce the binding of a second iron ion at the active site. Following analysis of small-molecule iron complexes and application of non-denaturing protein mass spectrometry to assess PHD2·iron·inhibitor stoichiometry, selected diacylhydrazines were identified as PHD2 inhibitors that induce the binding of a second iron ion. Some compounds were shown to inhibit the HIF hydroxylases in human hepatoma and renal carcinoma cell lines.

  翻译结果： 对缺氧诱导因子（HIF）脯氨酰羟化酶（PHD或EGLN酶）的抑制在治疗贫血和缺血相关疾病方面备受关注。大多数PHD抑制剂通过结合单个亚铁离子并与2-氧代戊二酸（2OG）共底物竞争结合PHD活性位点来发挥作用。非特异性铁螯合剂也能在体外和细胞内抑制PHD。我们报告了双作用PHD抑制剂的鉴定，这些抑制剂不仅与活性位点的铁结合，还能诱导在活性位点上结合第二个铁离子。通过对小分子铁络合物的分析并在非变性蛋白质谱法中评估PHD2·铁·抑制剂的比例后，鉴定出某些二酰基联氨为诱导第二个铁离子结合的PHD2抑制剂。有些化合物被证明能抑制人类肝癌和肾癌细胞系中的HIF羟化酶。
• Conversion of amides to esters by the nickel-catalysed activation of amide C–N bonds
  作者：Liana Hie、Noah F. Fine Nathel、Tejas K. Shah、Emma L. Baker、Xin Hong、Yun-Fang Yang、Peng Liu、K. N. Houk、Neil K. Garg

  DOI：10.1038/nature14615

  日期：2015.8

  Although enzymes are able to cleave amide bonds in nature, it is difficult to selectively break the carbon–nitrogen bond of an amide using synthetic chemistry; now the activation and cleavage of these bonds using nickel catalysts is used to convert amides to esters. Although enzymes are able to cleave amide bonds in nature, it is difficult to selectively break the carbon–nitrogen bond of an amide using synthetic chemistry. In this paper the authors demonstrate that amide C–N bonds can be activated and cleaved using nickel catalysts. They used this methodology to convert amides to esters, which is a challenging and underdeveloped transformation. Amides are common functional groups that have been studied for more than a century1. They are the key building blocks of proteins and are present in a broad range of other natural and synthetic compounds. Amides are known to be poor electrophiles, which is typically attributed to the resonance stability of the amide bond1,2. Although amides can readily be cleaved by enzymes such as proteases3, it is difficult to selectively break the carbon–nitrogen bond of an amide using synthetic chemistry. Here we demonstrate that amide carbon–nitrogen bonds can be activated and cleaved using nickel catalysts. We use this methodology to convert amides to esters, which is a challenging and underdeveloped transformation. The reaction methodology proceeds under exceptionally mild reaction conditions, and avoids the use of a large excess of an alcohol nucleophile. Density functional theory calculations provide insight into the thermodynamics and catalytic cycle of the amide-to-ester transformation. Our results provide a way to harness amide functional groups as synthetic building blocks and are expected to lead to the further use of amides in the construction of carbon–heteroatom or carbon–carbon bonds using non-precious-metal catalysis.

  尽管酶能够在自然界中断裂酰胺键，但利用合成化学选择性地打破酰胺的碳—氮键却很困难；现在，使用镍催化剂激活和断裂这些键被用于将酰胺转化为酯。本文作者证明，酰胺C—N键可以使用镍催化剂激活和断裂。他们利用这种方法将酰胺转化为酯，这是一种具有挑战性且发展不足的转化。酰胺是一类常见的官能团，一个多世纪以来一直被研究。它们是蛋白质的关键构建模块，存在于广泛的天然和合成化合物中。酰胺被认为是一种差的亲电试剂，这通常归因于酰胺键的共振稳定性。尽管酶如蛋白酶可以轻易地断裂酰胺，但利用合成化学选择性地打破酰胺的碳—氮键却很困难。在这里，我们证明酰胺碳—氮键可以使用镍催化剂激活和断裂。我们利用这种方法将酰胺转化为酯，这是一种具有挑战性且发展不足的转化。反应方法在极其温和的反应条件下进行，并避免了使用大量过量的醇亲核试剂。密度泛函理论计算为酰胺到酯转化的热力学和催化循环提供了见解。我们的结果为利用酰胺官能团作为合成构建块提供了一种方法，并有望进一步在非贵金属催化的碳—杂原子或碳—碳键构建中使用酰胺。
• [EN] INHIBITORS OF MLH1 AND/OR PMS2 FOR CANCER TREATMENT<br/>[FR] INHIBITEURS DE MLH1 ET/OU PMS2 POUR LE TRAITEMENT DU CANCER
  申请人：NEOPHORE LTD

  公开号：WO2021245405A1

  公开（公告）日：2021-12-09

  The present invention relates to compounds of Formula (I) that target the MLH1 and/or PMS2 proteins that are components of the DNA Mismatch Repair (MMR) process: Formula (I) wherein R1, R2, R3, R4, R6 and R10 are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which MLH1 and/or PMS2 activity is implicated.

  本发明涉及式（I）的化合物，该化合物靶向DNA错配修复（MMR）过程的MLH1和/或PMS2蛋白质：式（I）其中R1、R2、R3、R4、R6和R10如本文所定义。本发明还涉及制备这些化合物的方法，包括它们的药物组合物，以及它们在治疗增殖性疾病（如癌症）以及MLH1和/或PMS2活性涉及的其他疾病或病况中的用途。
• Substituted 6,11-ethano-6,11-dihydrobenzo[b] quinolizinium salts and
  申请人：Sterling Winthrop Inc.

  公开号：US05554620A1

  公开（公告）日：1996-09-10

  Substituted 6,11-ethano-6,11-dihydrobenzo[b]quinolizinium salts, pharmaceutical compositions containing them, and methods for the treatment of neurodegenerative disorders or neurotoxic injuries utilizing them, wherein the substituted 6,11-ethano-6,11-dihydrobenzo[b]quinolizinium salts have the formula: ##STR1## wherein: R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, X and p are as defined in the specification.

  替代的6,11-乙烷-6,11-二氢苯并[b]喹啉盐，含有它们的药物组合物，以及利用它们治疗神经退行性疾病或神经毒性损伤的方法，其中替代的6,11-乙烷-6,11-二氢苯并[b]喹啉盐具有以下结构式：##STR1## 其中：R.sup.1、R.sup.2、R.sup.3、R.sup.4、R.sup.5、R.sup.6、R.sup.7、X 和 p 如规范中所定义。
• Kinetic Modeling of the Nickel-Catalyzed Esterification of Amides
  作者：Nicholas A. Weires、Daniel D. Caspi、Neil K. Garg

  DOI：10.1021/acscatal.7b01444

  日期：2017.7.7

  Nickel-catalyzed coupling reactions provide exciting tools in chemical synthesis. However, most methodologies in this area require high catalyst loadings, which commonly range from 10–20 mol % nickel. Through an academic-industrial collaboration, we demonstrate that kinetic modeling can be used strategically to overcome this problem, specifically within the context of the Ni-catalyzed conversion of amides

  镍催化的偶联反应为化学合成提供了令人兴奋的工具。但是，该领域中的大多数方法都需要高催化剂负载量，通常镍含量为10-20 mol％。通过学术界和工业界的合作，我们证明了动力学模型可以策略性地用于克服这一问题，特别是在镍催化的酰胺转化为酯的背景下。仅使用0.4摩尔％的镍，该方法成功应用于多克级耦合中，凸显了这一努力的影响。