3-[2-[2-[2-(2-叠氮基乙氧基)乙氧基]乙氧基]乙氧基]丙酸 | 1257063-35-6

• 物质功能分类: 生物 - 细胞培养 - 添加剂
• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 中文名称: 3-[2-[2-[2-(2-叠氮基乙氧基)乙氧基]乙氧基]乙氧基]丙酸
• 中文别名: 15-叠氮基-4,7,10,13-四氧杂十五烷酸
• 英文名称: 15-azido-4,7,10,13-tetraoxapentadecanoic acid
• 英文别名: 1-azido-3,6,9,12-tetraoxapentadecan-15-oic acid；Azido-Peg4 acid；Azido-PEG4-acid；3-[2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]ethoxy]propanoic acid
• CAS: 1257063-35-6
• 化学式: C₁₁H₂₁N₃O₆
• 分子量: 291.304
• InChiKey: BODPHGOBXPGJKO-UHFFFAOYSA-N

物化性质

• 溶解度：
  DMSO：100 mg/mL（343.29 mM；需要超声波）

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  20
• 可旋转键数：
  15
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  88.6
• 氢给体数：
  1
• 氢受体数：
  8

安全信息

• WGK Germany：
  3
• 储存条件：
  -20°C下存放于惰性气体中，并避免光照、潮湿和加热（可能导致分解）。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
N3-Peg(4)-cooh
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.
N3-Peg(4)-cooh
Ingredient name:
CAS number: 1257063-35-6

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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: C11H21N3O6
Molecular weight: 291.3

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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

概述

15-叠氮基-4,7,10,13-四氧杂十五烷酸是一种有机中间体，有文献报道它可以用于制备自杀式连接子。这种自杀式连接子能够将念珠藻素-55连接至单克隆抗体或肽制成的缀合物，从而高度有效地对抗肿瘤细胞。

制备

将15-叠氮基-4,7,10,13-四氧代十五烷酸叔丁酯(0.22g；0.63mmol)溶于纯DCM (5mL)中，然后添加TFA(5mL)。在室温下搅拌1.5小时后，在真空中除去挥发性化合物，并将残余物溶于二乙醚(10mL)中并蒸发溶剂（重复2次）。最后，溶液被浓缩至干燥，获得无色油形式的15-叠氮基-4,7,10,13-四氧杂十五烷酸(0.18g；0.62mmol；98%)。

生物活性

Azido-PEG4-C2-acid 是一种基于PEG 的 PROTAC 连接子，可用于合成vRucaparib-TP4。此外，它也是一种不可降解的含 4 个单元 PEG 的 ADC 连接子，可用于合成抗体偶联药物 (ADC)。

体外研究

PROTACs 包含两种不同的配体，由一种连接子连接起来；一个是E3泛素连接酶配体，另一个是目标蛋白的配体。PROTACs 利用细胞内的泛素-蛋白酶体系统选择性地降解目标蛋白。

ADC 由一个通过 ADC 连接子与 ADC 细胞毒剂相连的抗体组成。

反应信息

• 作为反应物：
  描述：

  3-[2-[2-[2-(2-叠氮基乙氧基)乙氧基]乙氧基]乙氧基]丙酸 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 20.0 ℃ 、100.0 kPa 条件下， 反应 16.0h， 以98%的产率得到3-[2-[2-[2-(2-氨基乙氧基)乙氧基]乙氧基]乙氧基]丙酸
  参考文献：
  名称：

  IEDDA生物正交系统的优化：改善反式-环辛烯/四嗪相互作用的有效方法。

  摘要：

  使用逆电子需求Diels-Alder环加成法（IEDDA）进行放射免疫治疗（RIT）的抗体预靶向方法，构成了一种针对实体癌的新兴治疗学方法。但是，IEDDA预靶向尚未达到临床试验。IEDDA策略的主要局限性很大程度上取决于反式环辛烯（TCO）的稳定性。实际上，TCO可能异构化成更稳定但不反应的顺式环辛烯（CCO），导致IEDDA效率急剧下降。因此，我们已经开发了有效且可重复的合成途径以及（PEG化的）TCO衍生物的分析跟进，为抗体修饰提供了高TCO异构纯度。我们已经建立了一个原始工艺，以限制在单克隆抗体的功能化之前允许TCO异构化为CCO，以允许高TCO /四嗪环加成。

  DOI：

  10.1016/j.ejmech.2020.112574
• 作为产物：
  描述：

  11-azido-3,6,9-trioxa-undecanyl p-toluenesulfonate 在 Jones reagent 、 sodium hydride 作用下， 以 四氢呋喃 、 丙酮 、 mineral oil 为溶剂， 反应 50.75h， 生成 3-[2-[2-[2-(2-叠氮基乙氧基)乙氧基]乙氧基]乙氧基]丙酸
  参考文献：
  名称：

  IEDDA生物正交系统的优化：改善反式-环辛烯/四嗪相互作用的有效方法。

  摘要：

  使用逆电子需求Diels-Alder环加成法（IEDDA）进行放射免疫治疗（RIT）的抗体预靶向方法，构成了一种针对实体癌的新兴治疗学方法。但是，IEDDA预靶向尚未达到临床试验。IEDDA策略的主要局限性很大程度上取决于反式环辛烯（TCO）的稳定性。实际上，TCO可能异构化成更稳定但不反应的顺式环辛烯（CCO），导致IEDDA效率急剧下降。因此，我们已经开发了有效且可重复的合成途径以及（PEG化的）TCO衍生物的分析跟进，为抗体修饰提供了高TCO异构纯度。我们已经建立了一个原始工艺，以限制在单克隆抗体的功能化之前允许TCO异构化为CCO，以允许高TCO /四嗪环加成。

  DOI：

  10.1016/j.ejmech.2020.112574

文献信息

• [EN] LEVORPHANOL PRODRUGS AND PROCESSES FOR MAKING AND USING THEM<br/>[FR] PROMÉDICAMENTS DE LEVORANOL ET LEURS PROCÉDÉS DE FABRICATION ET D'UTILISATION
  申请人：KEMPHARM INC

  公开号：WO2018191472A1

  公开（公告）日：2018-10-18

  The presently described technology provides compositions of one or more of oxoacids, polyethylene glycols, and vitamin compounds chemically conjugated to levorphanol ((-)-17-methylmorphinan-3-ol) to form novel prodrugs and compositions of levorphanol.

  目前描述的技术提供了一种或多种羟基酸、聚乙二醇和维生素化合物与左旋吗啡醇((-)-17-甲基吗啡-3-醇)在化学上结合形成新型前药和左旋吗啡的组合物。
• 一种喜树碱-抗体偶联物
  申请人：四川百利药业有限责任公司

  公开号：CN109106951A

  公开（公告）日：2019-01-01

  本发明公开了一种喜树碱‑抗体偶联物，该类ADC药物可有效提高其载药量，同时避免上述聚集现象发生，改善药物PK，在体内模型中获得理想的药效。
• [EN] DEXTRORPHAN PRODRUGS AND PROCESSES FOR MAKING AND USING THEM<br/>[FR] PROMÉDICAMENTS DE DEXTRORPHANE ET LEURS PROCÉDÉS DE FABRICATION ET D'UTILISATION
  申请人：KEMPHARM INC

  公开号：WO2018191477A1

  公开（公告）日：2018-10-18

  The presently described technology provides compositions of one or more of oxoacids, polyethylene glycols, and/or vitamin compounds chemically conjugated to dextrorphan, (+)-17-methylmorphinan-3-ol), to form novel prodrugs and compositions of dextrorphan.

  目前描述的技术提供了将一种或多种羟基酸、聚乙二醇和/或维生素化学共轭到右旋丙啡醇（(+)-17-甲基吗啡酮-3-醇）上，形成新型前药和右旋丙啡醇组合物的配方。
• Near-IR Light-Mediated Cleavage of Antibody-Drug Conjugates Using Cyanine Photocages
  作者：Roger R. Nani、Alexander P. Gorka、Tadanobu Nagaya、Hisataka Kobayashi、Martin J. Schnermann

  DOI：10.1002/anie.201507391

  日期：2015.11.9

  clinical application of antibody drug conjugates (ADCs), novel cleavage strategies that provide improved selectivity are still needed. Herein is reported the first approach that uses near‐IR light to cleave a small molecule from a biomacromolecule, and its application to the problem of ADC linkage. The preparation of cyanine antibody conjugates, drug cleavage mediated by 690 nm light, and initial in

  尽管在抗体药物缀合物（ADC）的临床应用方面取得了重大进展，但仍需要提供改进选择性的新型切割策略。本文报道了第一种使用近红外光从生物大分子中裂解小分子的方法，并将其应用于ADC连锁问题。描述了花青抗体结合物的制备，690 nm光介导的药物裂解以及初步的体内和体外评估。这些研究为开发近红外光可裂解的连接子策略提供了关键的化学基础。
• [EN] CRYPTOPHYCIN-BASED ANTIBODY-DRUG CONJUGATES WITH NOVEL SELF-IMMOLATIVE LINKERS<br/>[FR] CONJUGUÉS MÉDICAMENT-ANTICORPS À BASE DE CRYPTOPHYCINE AVEC NOUVEAUX LIEURS AUTO-IMMOLABLES
  申请人：EXIRIS S R L

  公开号：WO2016146638A1

  公开（公告）日：2016-09-22

  The present invention relates to antibody- or peptide-drug conjugate compounds where one or more cryptophycin derivatives (macrocyclic depsipeptide) are covalently attached by a self-immolative linker which binds to one or more tumor-associated antigens or cell-surface receptors. The linker contains a cleavage site for proteases and a dipeptide unit able to form a diketopiperazine. These compounds may be useful in methods of diagnosis or treatment of cancer, and other diseases and disorders, such as immune or infective diseases.

  本发明涉及抗体或肽药物结合物，其中一个或多个隐花链霉素衍生物（大环脱氨肽）通过一种自解离连接剂共价结合到一个或多个肿瘤相关抗原或细胞表面受体上。连接剂包含蛋白酶的裂解位点和能够形成二肽环的二肽单元。这些化合物可能在癌症的诊断或治疗方法以及其他疾病和紊乱，如免疫或感染性疾病中有用。