N-芴甲氧羰基环己基-L-高丙氨酸 | 269078-73-1

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 丙氨酸类衍生物
• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 中文名称: N-芴甲氧羰基环己基-L-高丙氨酸
• 中文别名: Fmoc-L-环己基丁氨酸；Fmoc-L-2-氨基-4-环己基丁酸
• 英文名称: (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-cyclohexylbutanoic acid
• 英文别名: Fmoc-L-homoCha-OH；Fmoc-L-Homocyclohexylalanine；(2S)-4-cyclohexyl-2-(9H-fluoren-9-ylmethoxycarbonylamino)butanoic acid
• CAS: 269078-73-1
• 化学式: C₂₅H₂₉NO₄
• 分子量: 407.51
• InChiKey: KYXCSTPOLMVGMS-QHCPKHFHSA-N

物化性质

• 沸点：
  618.1±38.0 °C(Predicted)
• 密度：
  1.192±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  29225090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  存储温度应保持在0-8°C之间。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: Fmoc-l-homocyclohexylalanine
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: Fmoc-l-homocyclohexylalanine
CAS number: 269078-73-1

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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: C25H29NO4
Molecular weight: 407.5

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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：

  N-芴甲氧羰基环己基-L-高丙氨酸 在 哌啶 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 22.5h， 生成 (S)-2-amino-4-cyclohexyl-N-(pentan-3-yl)butanamide
  参考文献：
  名称：

  Selective targeting of the αC and DFG-out pocket in p38 MAPK

  摘要：

  The p38 MAPK cascade is a key signaling pathway linked to a multitude of physiological functions and of central importance in inflammatory and autoimmune diseases. Although studied extensively, little is known about how conformation-specific inhibitors alter signaling outcomes. Here, we have explored the highly dynamic back pocket of p38 MAPK with allosteric urea fragments. However, screening against known off-targets showed that these fragments maintained the selectivity issues of their parent compound BIRB-796, while combination with the hinge-binding motif of VPC-00628 greatly enhanced inhibitor selectivity. Further efforts focused therefore on the exploration of the αC-out pocket of p38 MAPK, yielding compound 137 as a highly selective type-II inhibitor. Even though 137 is structurally related to a recent p38 type-II chemical probe, SR-318, the data presented here provide valuable insights into back-pocket interactions that are not addressed in SR-318 and it provides an alternative chemical tool with good cellular activity targeting also the p38 back pocket.

  DOI：

  10.1016/j.ejmech.2020.112721

文献信息

• Selective Substrates and Activity-Based Probes for Imaging of the Human Constitutive 20S Proteasome in Cells and Blood Samples
  作者：Wioletta Rut、Marcin Poręba、Paulina Kasperkiewicz、Scott J. Snipas、Marcin Drąg

  DOI：10.1021/acs.jmedchem.8b00026

  日期：2018.6.28

  the HyCoSuL approach, we designed and synthesized novel and selective fluorogenic substrates for each of these three constitutive 20S proteasome activities and applied them to assess inhibition of proteasome subunits by MG-132 and a clinically used inhibitor bortezomib. Our results confirm the utility of designed substrates in biochemical assays. Furthermore, selective peptide sequences obtained in this

  蛋白酶体是维持蛋白质稳态的关键酶复合物。蛋白酶体功能紊乱导致包括癌症，自身免疫和神经退行性疾病在内的病理。因此，蛋白酶体构成药物开发的极好的分子靶标。在这里，我们使用HyCoSuL方法为这三个20S组成型蛋白酶体活性中的每一个设计和合成了新颖的选择性荧光底物，并将它们应用于评估MG-132和临床使用的硼替佐米对蛋白酶体亚基的抑制作用。我们的结果证实了设计的底物在生化分析中的实用性。此外，以此方式获得的选择性肽序列用于构建荧光团标记的基于活性的探针，然后用于同时检测HEK-293F细胞和红细胞裂解液中的每个20S组成型蛋白酶体亚基。总体而言，我们描述了一种简单而快速的方法，可用于测量全血样本中20S组成型蛋白酶体的活性，该方法可以早期诊断与异常上调的蛋白酶体活性有关的病理状态。
• Development of a Selective Dual Discoidin Domain Receptor (DDR)/p38 Kinase Chemical Probe
  作者：Sandra Röhm、Benedict-Tilman Berger、Martin Schröder、Deep Chatterjee、Sebastian Mathea、Andreas C. Joerger、Daniel M. Pinkas、Joshua C. Bufton、Amelie Tjaden、Lohitesh Kovooru、Mark Kudolo、Christian Pohl、Alex N. Bullock、Susanne Müller、Stefan Laufer、Stefan Knapp

  DOI：10.1021/acs.jmedchem.1c00868

  日期：2021.9.23

  and various forms of cancer. Potent and selective inhibitors, so-called chemical probe compounds, have been developed to study DDR1/2 kinase signaling. However, these inhibitors showed undesired activity on other kinases such as the tyrosine protein kinase receptor TIE or tropomyosin receptor kinases, which are related to angiogenesis and neuronal toxicity. In this study, we optimized our recently published

  盘状蛋白结构域受体 1 和 2 (DDR1/2) 在纤维化疾病中发挥核心作用，例如肾和肺纤维化、动脉粥样硬化和各种形式的癌症。已开发出强效和选择性抑制剂，即所谓的化学探针化合物，用于研究 DDR1/2 激酶信号。然而，这些抑制剂对其他激酶（如酪氨酸蛋白激酶受体 TIE 或原肌球蛋白受体激酶）显示出不希望有的活性，这些激酶与血管生成和神经元毒性有关。在这项研究中，我们优化了我们最近发表的 p38 丝裂原活化蛋白激酶抑制剂7朝着有效的细胞活性双 DDR/p38 化学探针发展，并开发了一种结构相关的阴性对照。使用的结构引导设计方法提供了对 p38 的 P 环折叠过程以及非保守氨基酸的靶向如何调节抑制剂选择性的见解。开发和全面表征的 DDR/p38 探针30 (SR-302) 是研究 DDR 激酶在正常生理学和疾病发展中的作用的宝贵工具。
• Rapid, Structure-Based Exploration of Pipecolic Acid Amides as Novel Selective Antagonists of the FK506-Binding Protein 51
  作者：Steffen Gaali、Xixi Feng、Andreas Hähle、Claudia Sippel、Andreas Bracher、Felix Hausch

  DOI：10.1021/acs.jmedchem.5b01355

  日期：2016.3.24

  However, drug-like parameters for these ligands remained unfavorable. In the present study, we replaced the potentially labile pipecolic ester group of previous FKBP51 ligands by various low molecular weight amides. This resulted in the first series of pipecolic acid amides, which had much lower molecular weights without affecting FKBP51 selectivity. We discovered a geminally substituted cyclopentyl

  FK506结合蛋白51（FKBP51）是压力激素受体的关键调节剂，并且是与压力相关的疾病的既定危险因素。FKBP51的药物开发受到结构相似但功能相反的同系物FKBP52的破坏。FKBP51和FKBP52之间的高选择性可以通过稳定最近发现的FKBP51有利构象的配体来实现。然而，这些配体的药物样参数仍然是不利的。在本研究中，我们用各种低分子量酰胺取代了以前的FKBP51配体的潜在不稳定的胡椒酸酯基。这产生了第一系列的胡椒酸酰胺，其具有低得多的分子量而不影响FKBP51的选择性。
• Antiprotozoal Structure–Activity Relationships of Synthetic Leucinostatin Derivatives and Elucidation of their Mode of Action
  作者：Michael Brand、Lei Wang、Stefano Agnello、Silvia Gazzola、Flavio M. Gall、Luka Raguž、Marcel Kaiser、Remo S. Schmidt、Amélie Ritschl、Jennifer Jelk、Andrew Hemphill、Pascal Mäser、Peter Bütikofer、Michael Adams、Rainer Riedl

  DOI：10.1002/anie.202102153

  日期：2021.7.5

  understanding. The antiprotozoal SAR matched SAR in phospholipid liposomes, where membrane integrity, leaking, and dynamics were studied. The mode of action is discussed based on a structure–activity analysis of derivatives in efficacy, ultrastructural studies in T. brucei, and artificial membrane models, mimicking membrane stability and membrane potential. The main site of antiprotozoal action of natural

  Leucinostatin A 是迄今为止描述的最有效的抗原虫化合物之一，但人们对其构效关系 (SAR) 知之甚少。我们使用布氏锥虫作为原生动物模型生物来测试合成修饰的衍生物，得到简化但活性相同的化合物2 (ZHAWOC6025) 和4 (ZHAWOC6027)，随后在分子的所有区域进行修饰，以获得深入的 SAR 了解。抗原虫 SAR 与磷脂脂质体中的 SAR 相匹配，研究了膜的完整性、渗漏和动力学。基于衍生物功效的结构活性分析、 T. brucei的超微结构研究以及模拟膜稳定性和膜电位的人工膜模型，讨论了作用模式。超微结构分析、电子显微镜和线粒体染色表明，天然和合成的亮氨抑素的抗原虫作用的主要位点在于线粒体内膜的不稳定。布氏锥虫的长期亚致死暴露（200 次传代）和 12'000 个突变体的 siRNA 筛选未显示出对合成衍生物产生抗性的迹象。
• Novel Ergopeptides as Dual Ligands for Adenosine and Dopamine Receptors
  作者：Marc Vendrell、Ester Angulo、Vicent Casadó、Carme Lluis、Rafael Franco、Fernando Albericio、Miriam Royo

  DOI：10.1021/jm060947x

  日期：2007.6.1

  prepared dual ligands acting on adenosine and dopamine receptors by applying a combinatorial approach based on the ergolene privileged structure. The potency and efficacy of these novel compounds were determined by radioligand binding studies and intracellular cAMP production assays in cells expressing adenosine and dopamine receptors. Selected compounds displayed dual dopamine agonist and adenosine

  多价配体是有前途的药理学工具，对多种疾病的治疗可能比高度选择性的单靶标药物更为有效。目前正在评估使用多巴胺能激动剂和腺苷能拮抗剂的联合疗法，以治疗帕金森氏病。[（a）Kanda，T .; 等。经验值 神经元。2000、162、321-327。（b）詹纳，体育专家。投资。药物，2005，14，729-738。（c）Kase，H .；等。Neurology 2003，61（Suppl 6），S97-S100。]在这里，我们通过基于麦角蛋白优先结构的组合方法制备了作用于腺苷和多巴胺受体的双重配体。这些新化合物的效力和功效通过放射性配体结合研究和表达腺苷和多巴胺受体的细胞内细胞内cAMP产生测定来确定。选定的化合物表现出双重多巴胺激动剂和腺苷拮抗剂活性。具有这种药理学特征的分子对于研究中枢神经系统中的多巴胺-腺苷串扰以及测试多价药物对帕金森氏病的治疗潜力具有潜在的实用性。