3-氨基异烟酸甲酯 | 55279-30-6

• 物质功能分类: 医药中间体 - 吡啶类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 3-氨基异烟酸甲酯
• 中文别名: 3-氨基-4-吡啶甲酸甲酯；3-氨基-4-吡啶羧酸甲酯；3-氨基吡啶-4-羧酸乙酯；3-氨基吡啶-4-甲酸甲酯；3-氨基吡啶-4-羧酸甲酯
• 英文名称: methyl 3-aminoisonicotinate
• 英文别名: methyl 3-aminopyridine-4-carboxylate；3-aminoisonicotinic acid methyl ester
• CAS: 55279-30-6
• 化学式: C₇H₈N₂O₂
• mdl: MFCD02082535
• 分子量: 152.153
• InChiKey: XLQIGLBALJNHKR-UHFFFAOYSA-N

物化性质

• 熔点：
  84-86
• 沸点：
  292.5±20.0 °C(Predicted)
• 密度：
  1.238±0.06 g/cm3(Predicted)
• 溶解度：
  >22.8 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.142
• 拓扑面积：
  65.2
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S24/25
• 危险类别码：
  R22,R36/38
• 海关编码：
  2933399090
• 危险性防范说明：
  P273
• 危险性描述：
  H302,H412
• 储存条件：
  室温

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Methyl 3-aminoisonicotinate
Product Name:
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H315: Causes skin irritation
H319: Causes serious eye irritation
H335: May cause respiratory irritation
P261: Avoid breathing dust/fume/gas/mist/vapours/spray
Wear protective gloves/protective clothing/eye protection/face protection
P280:
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present
and easy to do – continue rinsing
P304+P340: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing
P405: Store locked up

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Section 3. Composition/information on ingredients.
Methyl 3-aminoisonicotinate
Ingredient name:
CAS number: 55279-30-6

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Section 4. First aid measures
Immediately wash skin with copious amounts of water for at least 15 minutes while removing
Skin contact:
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.
Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.
Ingestion:

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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.
Storage: Store in closed vessels, refrigerated.

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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
Not specified
Appearance:
Boiling point: No data
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C7H8N2O2
Molecular weight: 152.2

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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

制备方法与用途

3-氨基异烟酸甲酯的制备

3-氨基异烟酸甲酯是一种常用的化工原料。传统合成方法使用3,4-吡啶二羧酸为原料，先与乙酰胺在醋酐催化下高温酰胺化得到吡啶二甲酰亚胺，再经霍夫曼降解、酯化得到目标化合物。

1. 3-溴-4-吡啶羧酸的合成

将50g（0.41mol）4-吡啶羧酸与150ml甲醇加入反应瓶中，在20℃下搅拌，滴加71.5g（0.45mol）溴素。加毕后升温至40-45℃保温5小时，冷却至室温后过滤、烘干，得3-溴-4-吡啶羧酸76.3g，收率93.5%，HPLC纯度为97.8%。

2. 3-氨基-4-吡啶羧酸的合成

将50g（0.25mol）3-溴-4-吡啶羧酸分批加入100ml 18%氨水中，加入碘化亚铜1g（0.0053mol）。在高压釜中密闭升温至100-105℃搅拌反应6小时。冷却后用26%盐酸调pH至5.5-6，过滤、烘干得3-氨基-4-吡啶羧酸32.1g，收率93%，HPLC纯度为99.5%。

3. 3-氨基异烟酸甲酯的合成

将3-氨基-4-吡啶羧酸50g（0.36mol）与300ml甲醇加入反应瓶中，在20℃下滴加10g硫酸。加毕后升温回流12小时，负压浓缩甲醇至无液体流出。冷却至室温后用18%氨水调pH至7-8，加水稀释并搅拌冷却至0-5℃过滤、烘干得3-氨基异烟酸甲酯48.9g，收率89.3%，HPLC纯度为99.3%。

反应信息

• 作为反应物：
  描述：

  3-氨基异烟酸甲酯 在 三氟甲磺酸 、 potassium iodide 、 sodium nitrite 作用下， 以 水 、 乙腈 为溶剂， 反应 1.25h， 以85%的产率得到3-碘异烟酸甲酯
  参考文献：
  名称：

  通过高强度的18 F标记配体（[ 18 F] UCB-H）的稳健和一步放射性合成，使突触囊泡糖蛋白2A（SV2A）的正电子发射断层扫描（PET）成像成为可能。

  摘要：

  本文中，我们描述了稳定的吡啶基（4-甲氧基苯基）碘鎓盐和的直接的合成第[ 18 F]的[一步法，全自动和cGMP的标准放射合成中放射性标记18 F] UCB-H（[ 18 F] 7），用于对突触小泡糖蛋白2A（SV2A）成像的PET示踪剂。超过1年的过程中，50个自动化生产提供的34±2％注射[ 18 F] 7从高达285吉贝（7.7次）[ 18F]在50分钟内氟化（未校正的放射化学产率，比活为815±185 GBq /μmol）。在常规，高活性和cGMP生产中成功实施了我们的合成策略，证明了其在大剂量[ 18 F] 7生产中的实用性和可靠性。除了可以通过SV2A成像对各种神经病理学进行高效且具有成本效益的临床研究以外，这项工作还进一步证明了碘鎓盐对于cGMP 18 F-PET示踪剂制造行业的真正价值，以及它们满足实际应用的能力。和该领域的法规要求。

  DOI：

  10.1021/acs.jmedchem.6b00905
• 作为产物：
  描述：

  异烟酸甲酯 在 sodium dithionite 、 乙醇 、 五氧化二氮 、 sodium hydrogensulfite 作用下， 以 甲醇 、 硝基甲烷 、 水 为溶剂， 反应 6.0h， 生成 3-氨基异烟酸甲酯
  参考文献：
  名称：

  吡啶底物的Friedländer缩合反应合成新型1,7-萘啶

  摘要：

  适当的吡啶基化合物（醛或酮）经历弗里德兰德缩合反应生成不同的1,7-萘啶的一般能力已得到证明。由3-氨基-4-乙酰基吡啶（6）和酮4（82％）制备2,4-二取代的1,7-萘啶8。也报道了吡啶基底物6的Friedländer自缩合反应。获得二聚体产物2-（3-氨基吡啶-4-基）-4-甲基-1,7-萘啶（7），收率为97％。2-芳基-和2,3-二芳基-1,7-萘啶（16，17，18）从3- aminoisonicotinaldehyde（制备13）和arylketones 4，14和15（28-71％）。通过改进的吡啶硝化方法可以容易地获得关键衬底6和13。J.杂环化​​学。（2011）。

  DOI：

  10.1002/jhet.657

文献信息

• SULFONAMIDE DERIVATIVE AND MEDICINAL USE THEREOF
  申请人：AJINOMOTO CO., LTD.

  公开号：US20150051395A1

  公开（公告）日：2015-02-19

  Provided are sulfonamide derivatives of a specific chemical structure in which a sulfonamide group having, as a substituent, a phenyl group or a heterocyclic group having a hetero atom(s) as a constituent element(s) is present at its terminal, and pharmaceutically acceptable salts thereof. These compounds are novel compounds having excellent α4 integrin-inhibitory action.

  提供的是具有特定化学结构的磺酰胺衍生物，在其末端有一个带有苯基或含杂原子的杂环基团作为取代基的磺酰胺基团，以及药用可接受的盐。这些化合物是具有卓越的α4整合素抑制作用的全新化合物。
• SULFONAMIDE DERIVATIVE AND PHARMACEUTICAL USE THEREOF
  申请人：Ajinomoto Co., Inc.

  公开号：US20160244451A1

  公开（公告）日：2016-08-25

  Provided is a sulfonamide derivative represented by the following general formula (1) and having an α4 integrin inhibitory effect with high selectivity with a low effect on α4β1 and a high effect on α4β7, or a pharmaceutically acceptable salt thereof (in the general formula (1), A, B, D, E, R 41 , and a to h are as described in the description).

  提供的是一种磺酰胺衍生物，其具有以下通式(1)表示，并具有对α4整合素抑制效果的高选择性，对α4β1影响小，对α4β7影响大，或其药用可接受盐（在通式(1)中，A、B、D、E、R 41 和a至h如描述中所述）。
• Potent, Selective, and Cell Active Protein Arginine Methyltransferase 5 (PRMT5) Inhibitor Developed by Structure-Based Virtual Screening and Hit Optimization
  作者：Ruifeng Mao、Jingwei Shao、Kongkai Zhu、Yuanyuan Zhang、Hong Ding、Chenhua Zhang、Zhe Shi、Hualiang Jiang、Dequn Sun、Wenhu Duan、Cheng Luo

  DOI：10.1021/acs.jmedchem.7b00587

  日期：2017.7.27

  been validated as an anticancer target in mantle cell lymphoma. In this study, we found a potent and selective PRMT5 inhibitor by performing structure-based virtual screening and hit optimization. The identified compound 17 (IC50 = 0.33 μM) exhibited a broad selectivity against a panel of other methyltransferases. The direct binding of 17 to PRMT5 was validated by surface plasmon resonance experiments

  PRMT5在多种细胞过程中起着重要作用，并在几种人类恶性肿瘤中被上调。此外，PRMT5已被确认为套细胞淋巴瘤的抗癌靶标。在这项研究中，我们通过执行基于结构的虚拟筛选和命中优化，发现了一种有效的选择性PRMT5抑制剂。鉴定出的化合物17（IC 50 = 0.33μM）对一组其他甲基转移酶表现出广泛的选择性。通过表面等离振子共振实验验证了17与PRMT5的直接结合，K d为0.987μM。动力学实验表明17是除底物以外的SAM竞争性抑制剂。另外17提示对MV4-11细胞具有选择性的抗增殖作用，进一步的研究表明，细胞抗肿瘤活性的机制是由于PRMT5介导的SmD3甲基化的抑制。17可能是一种有前途的先导化合物，可以进一步了解PRMT5，并可能有助于开发白血病适应症的治疗方法。
• [EN] INHIBITORS OF PHOSPHOLIPID SYNTHESIS AND METHODS OF USE<br/>[FR] INHIBITEURS DE LA SYNTHÈSE DES PHOSPHOLIPIDES ET PROCÉDÉS D'UTILISATION
  申请人：UNIV LELAND STANFORD JUNIOR

  公开号：WO2021035031A1

  公开（公告）日：2021-02-25

  Inhibitors of Glycerol 3-Phosphate Acyltransferase (GPAT) are provided; and methods of use in the treatment of cancer; and treatment of conditions relating to metabolic syndrome, hyperlipidemia, infection and inflammation.

  甘油3-磷酸酰基转移酶（GPAT）的抑制剂已提供；以及在癌症治疗中的使用方法；以及治疗与代谢综合征、高脂血症、感染和炎症相关的疾病的方法。
• Identification and Optimization of the First Highly Selective GLUT1 Inhibitor BAY-876
  作者：Holger Siebeneicher、Arwed Cleve、Hartmut Rehwinkel、Roland Neuhaus、Iring Heisler、Thomas Müller、Marcus Bauser、Bernd Buchmann

  DOI：10.1002/cmdc.201600276

  日期：2016.10.19

  these transporters should not be addressed by such an inhibitor. A high-throughput screen against a library of ∼3 million compounds was performed to find a small molecule with this challenging potency and selectivity profile. The N-(1H-pyrazol-4-yl)quinoline-4-carboxamides were identified as an excellent starting point for further compound optimization. After extensive structure-activity relationship explorations

  尽管众所周知的事实是，即使在正常的氧气供应条件下，促进性葡萄糖转运蛋白GLUT1仍是保证许多肿瘤实体葡萄糖消耗增加的关键因素之一（被称为Warburg效应），但仅进行了很少的努力寻找一种GLUT1选择性小分子抑制剂。由于GLUT1家族的其他转运蛋白都参与关键过程，因此此类抑制剂不应解决这些转运蛋白。针对约300万种化合物的库进行了高通量筛选，以发现具有这种具有挑战性的效能和选择性的小分子。N-（1H-吡唑-4-基）喹啉-4-羧酰胺被确定为进一步优化化合物的理想起点。经过广泛的构效关系探索后，获得了对GLUT2，GLUT3和GLUT4的选择性因子> 100的个位数纳摩尔抑制剂。最有前途的化合物BAY-876 [N4- [1-（4-氰基苄基）-5-甲基-3-（三氟甲基）-1H-吡唑-4-基] -7-氟喹啉-2,4-二甲酰胺]在体外具有良好的代谢稳定性，在体内具有较高的口服生物利用度。