(S)-1,2,3,4-四氢-1-萘甲酸 | 85977-52-2

• 物质功能分类: 医药中间体
• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: (S)-1,2,3,4-四氢-1-萘甲酸
• 中文别名: (S)-1,2,3,4-四氢萘甲酸；S-四氢萘甲酸；(S)-(-)-1,2,3,4-四氢-1-萘甲酸；S-1,2,3,4-四氢萘甲酸
• 英文名称: (S)-(-)-1,2,3,4-tetrahydro-1-naphthoic acid
• 英文别名: (S)-1,2,3,4-tetrahydronaphthalene-1-carboxylic acid；(S)-1,2,3,4-tetrahydronaphthoic acid；(S)-1,2,3,4-tetrahydro-1-naphthoic acid；(1S)-1,2,3,4-tetrahydronaphthalene-1-carboxylic acid
• CAS: 85977-52-2
• 化学式: C₁₁H₁₂O₂
• 分子量: 176.215
• InChiKey: VDLWTJCSPSUGOA-JTQLQIEISA-N

物化性质

• 熔点：
  54-56°C
• 沸点：
  54-56°C
• 密度：
  1.186±0.06 g/cm3(Predicted)
• 溶解度：
  溶于氯仿
• 稳定性/保质期：

  按照规定使用和贮存的物质不会分解，并且能避开氧化物。

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险品标志：
  Xi
• 海关编码：
  2916399090
• 危险性防范说明：
  P305+P351+P338
• 危险性描述：
  H302,H319

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: (S)-1,2,3,4-Tetrahydronaphthoic acid
Synonyms: (S)-(-)-1,2,3,4-Tetrahydro-1-naphthoic acid

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H302: Harmful if swallowed
H319: Causes serious eye irritation
H411: Toxic to aquatic life with long lasting effects
P273: Avoid release to the environment
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present
and easy to do – continue rinsing

---

Section 3. Composition/information on ingredients.
Ingredient name: (S)-1,2,3,4-Tetrahydronaphthoic acid
CAS number: 85977-52-2

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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.
Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
Eye contact:
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.
Storage: Store in closed vessels.

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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
No data
Boiling point:
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C11H12O2
Molecular weight: 176.2

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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.

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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

用途

(S)-(-)-1,2,3,4-四氢-1-萘甲酸是制备硼酸二肽蛋白酶抑制剂的中间体。

帕洛诺司琼中间体，用于抗肿瘤药物的生产。

反应信息

• 作为反应物：
  描述：

  (S)-1,2,3,4-四氢-1-萘甲酸 在 硫酸 、 C₃₃H₂₉FeMnN₂O₃P 、 氢气 、 potassium carbonate 作用下， 以 异丙醇 为溶剂， 50.0~60.0 ℃ 、5.0 MPa 条件下， 反应 37.0h， 生成 (S)-1-hydroxymethyl-1,2,3,4-tetrahydronaphthalene
  参考文献：
  名称：

  对映体纯酯的锰催化加氢

  摘要：

  锰的酯催化氢化反应已完成，TONs的用量高达1000，分别使用廉价，对环境无害的碳酸钾和简单的醇作为活化剂和溶剂。弱碱性条件导致良好的官能团耐受性，并能够氢化对映异构体富集的α-手性酯，而基本上不损失立体化学完整性。

  DOI：

  10.1021/acs.orglett.8b00864
• 作为产物：
  描述：

  1,2,3,4-四氢-1-萘甲酸 在 盐酸 作用下， 以 乙醇 、 水 、 乙酸乙酯 为溶剂， 反应 2.5h， 生成 (S)-1,2,3,4-四氢-1-萘甲酸
  参考文献：
  名称：

  一种高效拆分制备(S)-四氢-1-萘甲酸的方法

  摘要：

  本发明涉及一种式（I）所示的盐酸帕洛诺司琼关键中间体(S)‑1,2,3,4‑四氢‑1‑萘甲酸的制备方法，该方法包括以下步骤：以1,2,3,4‑四氢萘甲酸消旋体为原料加入拆分剂拆分，得到（S）‑1,2,3,4‑四氢萘甲酸与拆分剂形成的盐（III）和（R）‑1,2,3,4‑四氢萘甲酸与拆分剂形成的盐（IV）；再对化合物III和化合物IV分别进行解盐，得到化合物（I）和（II）；将化合物（II）在碱性条件下进行消旋，得到起始原料1,2,3,4‑四氢萘甲酸消旋体，继续按上述步骤拆分。如此循环，可以大大提高总体收率，降低生产成本，更有利于环境保护。本发明提供了一种与现有技术不同的，安全环保、操作简单、收率高、具有较大实用价值的盐酸帕洛诺司琼关键中间体的制备工艺。

  公开号：

  CN107382697A

文献信息

• Microscale Parallel Synthesis of Acylated Aminotriazoles Enabling the Development of Factor XIIa and Thrombin Inhibitors
  作者：Simon Platte、Marvin Korff、Lukas Imberg、Ilker Balicioglu、Catharina Erbacher、Jonas M. Will、Constantin G. Daniliuc、Uwe Karst、Dmitrii V. Kalinin

  DOI：10.1002/cmdc.202100431

  日期：2021.12.14

  approach toward N-acylated aminotriazoles is reported, enabling the compounds’ screening against FXIIa and thrombin. This approach afforded low-nanomolar FXIIa and thrombin inhibitors with no off-targeting of the other tested serine proteases. Selected compounds were shown to be covalent inhibitors of FXIIa and demonstrated anticoagulant properties in vitro, influencing the intrinsic blood coagulation

  抗凝剂进展：报道了一种 N-酰化氨基三唑的微量平行合成方法，使该化合物能够针对 FXIIa 和凝血酶进行筛选。这种方法提供了低纳摩尔浓度的 FXIIa 和凝血酶抑制剂，且其他测试的丝氨酸蛋白酶没有脱靶。选定的化合物被证明是 FXIIa 的共价抑制剂，并在体外表现出抗凝血特性，影响内在的凝血途径。
• Acylated 1<i>H</i>-1,2,4-Triazol-5-amines Targeting Human Coagulation Factor XIIa and Thrombin: Conventional and Microscale Synthesis, Anticoagulant Properties, and Mechanism of Action
  作者：Marvin Korff、Lukas Imberg、Jonas M. Will、Nico Bückreiß、Svetlana A. Kalinina、Benjamin M. Wenzel、Gregor A. Kastner、Constantin G. Daniliuc、Maximilian Barth、Ruzanna A. Ovsepyan、Kirill R. Butov、Hans-Ulrich Humpf、Matthias Lehr、Mikhail A. Panteleev、Antti Poso、Uwe Karst、Torsten Steinmetzer、Gerd Bendas、Dmitrii V. Kalinin

  DOI：10.1021/acs.jmedchem.0c01635

  日期：2020.11.12

  We herein report the conventional and microscale parallel synthesis of selective inhibitors of human blood coagulation factor XIIa and thrombin exhibiting a 1,2,4-triazol-5-amine scaffold. Structural variations of this scaffold allowed identifying derivative 21i, a potent 29 nM inhibitor of FXIIa, with improved selectivity over other tested serine proteases and also finding compound 21m with 27 nM

  我们在此报告了常规和微观并行合成的人类凝血因子XIIa和凝血酶的选择性抑制剂，这些抑制剂表现出1,2,4-三唑-5-胺骨架。该支架的结构变异允许鉴定衍生物21i（一种有效的FXIIa抑制剂29nM），具有比其他经过测试的丝氨酸蛋白酶更高的选择性，还可以发现化合物21m对凝血酶具有27 nM的抑制活性。首次证明酰化的1,2,4-三唑-5-胺具有抗凝特性，并具有影响凝血酶和癌细胞诱导的血小板凝集的能力。进行的质谱分析和分子建模使我们能够发现合成的抑制剂与FXIIa活性位点之间以前未知的相互作用，从而揭示了FXIIa抑制的机理细节。合成的化合物代表了开发新的抗血栓药物或化学工具以研究FXIIa和凝血酶在生理和病理过程中的作用的有希望的起点。
• [EN] AMINOACYLINDAZOLE IMMUNOMODULATORS FOR TREATMENT OF AUTOIMMUNE DISEASES<br/>[FR] IMMUNOMODULATEURS À BASE D'AMINOCYLINDAZOLE POUR LE TRAITEMENT DE MALADIES AUTO-IMMUNES
  申请人：UNIV ROCKEFELLER

  公开号：WO2017205296A1

  公开（公告）日：2017-11-30

  2-Acylindazole compounds of formula I or formula II are disclosed. These compounds inhibit Coagulation Factor XIIa. They are useful to treat autoimmune diseases.

  公开了式I或式II的2-酰基吲唑化合物。这些化合物抑制凝血因子XIIa。它们可用于治疗自身免疫疾病。
• Structure-Based Design of Inhibitors Selective for Human Proteasome β2c or β2i Subunits
  作者：Bo-Tao Xin、Eva M. Huber、Gerjan de Bruin、Wolfgang Heinemeyer、Elmer Maurits、Christofer Espinal、Yimeng Du、Marissa Janssens、Emily S. Weyburne、Alexei F. Kisselev、Bogdan I. Florea、Christoph Driessen、Gijsbert A. van der Marel、Michael Groll、Herman S. Overkleeft

  DOI：10.1021/acs.jmedchem.8b01884

  日期：2019.2.14

  Subunit-selective proteasome inhibitors are valuable tools to assess the biological and medicinal relevance of individual proteasome active sites. Whereas the inhibitors for the β1c, β1i, β5c, and β5i subunits exploit the differences in the substrate-binding channels identified by X-ray crystallography, compounds selectively targeting β2c or β2i could not yet be rationally designed because of the high structural

  亚单位选择性蛋白酶体抑制剂是评估单个蛋白酶体活性位点生物学和医学相关性的有价值的工具。尽管β1c，β1i，β5c和β5i亚基的抑制剂利用了X射线晶体学鉴定的底物结合通道的差异，但由于这些化合物的高度结构相似性，因此尚无法合理设计选择性靶向β2c或β2i的​​化合物两个亚单位。在这里，我们报告了一个化合物库的开发，化学合成和生物学筛选，该过程导致了对β2c和β2i选择性化合物LU-002c的鉴定（4； IC50β2c：8 nM，IC50β2i/β2c：40-倍数）和LU-002i（5; IC50β2i：220 nM，IC50β2c/β2i：45倍）。具有β2人源化酵母蛋白酶体的共晶体结构可可视化对于亚基特异性至关重要的蛋白质-配体相互作用。总而言之，有机合成，基于活性的蛋白质谱分析，酵母诱变和结构生物学使我们能够破译β2底物结合通道的显着差异，并完成了一组亚基选择性蛋白酶体抑制剂的研究。
• SPIRO COMPOUNDS
  申请人：F. Hoffmann-La Roche AG

  公开号：EP3578561A1

  公开（公告）日：2019-12-11

  The present invention provides compounds of formula I which bind to the ubiquitously expressed E3 ligase protein cereblon (CRBN) and alter the substrate specificity of the CRBN E3 ubiquitin ligase complex, resulting in breakdown of intrinsic downstream proteins. Present compounds are thus useful for the treatment of various cancers.

  本发明提供了一种公式I的化合物，该化合物与广泛表达的E3连接酶蛋白cereblon（CRBN）结合，并改变CRBN E3泛素连接酶复合物的底物特异性，导致内在下游蛋白的降解。因此，目前的化合物对于治疗各种癌症是有用的。