吗啉-4-基乙酸 | 3235-69-6

• 物质功能分类: 化学试剂 - 有机试剂 - 芳香酸
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 吗啉-4-基乙酸
• 中文别名: 4-吗啉乙酸；吗啉-4-乙酸；2-吗啉利诺乙酸；4-吗啡啉乙酸
• 英文名称: morpholin-4-ylacetic acid
• 英文别名: 2-morpholinoacetic acid；4-morpholineacetic acid；4-morpholinylacetic acid；2-morpholineacetic acid；4-morpholinoacetic acid；2-(morpholin-4-yl)acetic acid；morpholine-4-ylacetic acid；morpholine-4-acetic acid；2-Morpholin-4-ium-4-ylacetate
• CAS: 3235-69-6
• 化学式: C₆H₁₁NO₃
• mdl: MFCD00504633
• 分子量: 145.158
• InChiKey: VIWZVFVJPXTXPA-UHFFFAOYSA-N

物化性质

• 熔点：
  162-164℃
• 沸点：
  272℃
• 密度：
  1.202
• 闪点：
  118℃
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  -2.8
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.833
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 危险类别码：
  R36
• 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：
  2-8°C

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: Morpholin-4-yl-acetic acid
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: Morpholin-4-yl-acetic acid
CAS number: 3235-69-6

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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: C6H11NO3
Molecular weight: 145.2

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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

吗啉-4-基乙酸是合成卡非佐米的重要起始原料。卡非佐米是由Onyx制药公司研发的一种新型蛋白酶体抑制剂，继硼替佐米之后，对难治性骨髓瘤表现出显著疗效，用于治疗多发性骨髓瘤。

反应信息

• 作为反应物：
  描述：

  吗啉-4-基乙酸 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 2-morpholinoacetyl chloride
  参考文献：
  名称：

  Exploring the potential of the β-thiolactones in bioorganic chemistry

  摘要：

  一系列新型肽基β-硫内酯被合成并测试了其对多个人类癌细胞系的细胞毒性，结果表明它们比相应的β-内酯和β-内酰胺更具活性。所制备的几种β-硫内酯在体外表现出对人类组织蛋白酶B和L的强烈抑制活性。

  DOI：

  10.1039/c1ob05967j
• 作为产物：
  描述：

  4-吗啉基乙酸甲酯 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 以67 %的产率得到吗啉-4-基乙酸
  参考文献：
  名称：

  基于大麻二酚的前药：合成和生物评价

  摘要：

  大麻二酚 (CBD 1 ) 是美国 FDA 批准的一种非精神病性大麻素药物，用于治疗难治性癫痫，即 Lennox-Gastaut 和 Dravet 综合征。然而，其低水溶性和口服生物利用度可以通过施用高剂量来补偿，并且对具有改进特性的缀合物的需求不断增加。在这个方向上，目前的工作重点是合成基于 CBD 的前药，以解决溶解度和口服生物利用度差的问题。合成了几种基于 CBD 的前药，并通过一系列测定进行研究：即释放动力学（离体）、溶解度（体外）、化学稳定性（体外）、血浆稳定性（离体）、药代动力学（体内）、和功效研究（体内）。在合成的前药中，基于吗啉基 CBD 的前药3a和3aa显示出良好的释放行为、稳定性、更好的溶解度和血浆曲线。此外，候选前药3aa显示出更好的治疗效果。本研究确定了基于 CBD 的前药具有改善的理化特性和口服暴露。

  DOI：

  10.1021/acsmedchemlett.3c00461
• 作为试剂：
  描述：

  H-DL-hPhe-DL-Leu-DL-Phe-OBn.TFA 、 吗啉-4-基乙酸 在 吗啉-4-基乙酸 作用下， 以74.8% over 2 steps的产率得到(S) - 苄基2 - ((S)-4 - 甲基-2 - ((S)-2 - (2 - 吗啉油布乙酰氨基)-4 - 苯基丁酰胺基)戊酰氨基)-3 - 苯基丙
  参考文献：
  名称：

  Compounds for enzyme inhibition

  摘要：

  基于肽的化合物包括含杂原子的三元环，能够高效且选择性地抑制N-末端亲核（Ntn）水解酶的特定活性。所述的化合物可以不同地抑制具有多种活性的Ntn的活性。例如，20S蛋白酶体的胰凝乳样活性可以通过这些创新化合物进行选择性抑制。基于肽的化合物包括至少三个肽单元，环氧化物或环氮化物，以及N末端的功能化。除了其他治疗用途外，预计基于肽的化合物将显示出抗炎性和抑制细胞增殖的特性。

  公开号：

  US07232818B2

文献信息

• Ahp-Cyclodepsipeptide Inhibitors of Elastase: Lyngbyastatin 7 Stability, Scalable Synthesis, and Focused Library Analysis
  作者：Danmeng Luo、Hendrik Luesch

  DOI：10.1021/acsmedchemlett.9b00473

  日期：2020.4.9

  Due to the potency and selectivity of lyngbyastatin 7 in inhibiting neutrophil elastase, a serine protease involved in numerous diseases, this cyclodepsipeptide was considered as a promising lead and subjected to further developmental studies. Lyngbyastatin 7 displayed a favorable serum and microsomal stability profile. The large-scale synthesis of key building blocks was performed on gram scale with

  由于lyngbyastatin 7抑制嗜中性粒细胞弹性蛋白酶（一种参与多种疾病的丝氨酸蛋白酶）的效力和选择性，该环二肽被认为是有前途的先导，并受到了进一步的开发研究。Lyngbyastatin 7显示出良好的血清和微粒体稳定性。关键组成部分的大规模合成以克级进行，具有提高的产率和简化的纯化程序。为了定制复杂的结构，定义最小的药效基团，并调节铅支架的理化性质，设计并合成了第一个类似物先导库用于结构-活性关系研究。我们发现了侧链的重要作用，这表明对弹性蛋白酶抑制作用的最低结构要求超出了通常已知分别传达抗蛋白酶活性和弹性蛋白酶选择性的3-氨基-6-羟基-2-哌啶酮（Ahp）和2-氨基丁烯酸（Abu）部分。我们的研究将促进此类弹性蛋白酶抑制剂的设计和开发。
• Alpha-Ketoamide Inhibitors Of Cysteine Proteases
  申请人：Phelix Therapeutics

  公开号：US20190085024A1

  公开（公告）日：2019-03-21

  The disclosure provides compounds comprising a α-ketoamide linkage that is terminated on each end by an amino acid, such as compounds of Formula (I), wherein RA-RC are defined herein. Also provided are compositions containing these compounds and methods of inhibiting calpain activity, treating a calpain-mediated disorder, inhibiting cathepsin-B, cathepsin-L, cathepsin-S, or cathepsin-L activity, and methods of treating a cathepsin-B, cathepsin-L, cathepsin-S, or cathepsin-L mediated disorder using these compounds and compositions.

  该披露提供了包含α-酮酰胺键的化合物，该键在每端由氨基酸终止，例如式(I)中的化合物，其中RA-RC在此处定义。还提供了含有这些化合物的组合物以及抑制钙蛋白酶活性、治疗钙蛋白酶介导的疾病、抑制卡托普西-B、卡托普西-L、卡托普西-S或卡托普西-L活性的方法，以及使用这些化合物和组合物治疗卡托普西-B、卡托普西-L、卡托普西-S或卡托普西-L介导的疾病的方法。
• CYCLOPROPYLAMINES AS LSD1 INHIBITORS
  申请人：Incyte Corporation

  公开号：US20150225379A1

  公开（公告）日：2015-08-13

  The present invention is directed to cyclopropylamine derivatives which are LSD1 inhibitors useful in the treatment of diseases such as cancer.

  本发明涉及环丙胺衍生物，这些衍生物是LSD1抑制剂，可用于治疗癌症等疾病。
• [EN] COMPOUNDS USEFUL AS CSF1 MODULATORS<br/>[FR] COMPOSÉS UTILES EN TANT QUE MODULATEURS DU FACTEUR 1 DE STIMULATION DE COLONIES
  申请人：REDX PHARMA PLC

  公开号：WO2016051193A1

  公开（公告）日：2016-04-07

  This invention relates to novel compounds and to pharmaceutical compositions comprising the novel compounds. More specifically, the invention relates to compounds useful as Colony Stimulating Factor 1 Receptor (cFMS) modulators (e.g. cFMS inhibitors). This invention also relates to processes for preparing the compounds, uses of the compounds in treatment and methods of treatment employing the compounds. Specifically, the invention relates to the use of the compounds for the treatment of cancer and autoimmune diseases.

  这项发明涉及新颖化合物以及包含这些新颖化合物的药物组合物。更具体地，该发明涉及用作集落刺激因子1受体（cFMS）调节剂（例如cFMS抑制剂）的化合物。这项发明还涉及制备这些化合物的方法，这些化合物在治疗中的用途以及利用这些化合物进行治疗的方法。具体而言，该发明涉及利用这些化合物治疗癌症和自身免疫性疾病。
• [EN] INHIBITORS OF THE WNT SIGNALLING PATHWAYS<br/>[FR] INHIBITEURS DES VOIES DE SIGNALISATION WNT
  申请人：BAYER PHARMA AG

  公开号：WO2015140196A1

  公开（公告）日：2015-09-24

  The present invention relates to inhibitors of the Wnt signalling pathways of general formula (I) as described and defined herein, to methods of preparing said compounds, to intermediate compounds useful for preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of a hyper- proliferative disorder, as a sole agent or in combination with other active ingredients.

  本发明涉及通式（I）所述和定义的Wnt信号通路抑制剂，涉及制备该类化合物的方法，有用于制备该类化合物的中间化合物，包含该类化合物的药物组合物和组合物，以及利用该类化合物制造用于治疗或预防疾病的药物组合物，特别是用作唯一药剂或与其他活性成分组合使用时，用于治疗或预防过度增殖性疾病。