芴甲氧羰酰基环己基甘氨酸 | 161321-36-4

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 甘氨酸类衍生物
• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 中文名称: 芴甲氧羰酰基环己基甘氨酸
• 中文别名: Fmoc-L-环己基氨基乙酸；N-芴甲氧羰基-L-环己基甘氨酸；Fmoc-L-环己基甘氨酸
• 英文名称: S-(((9H-fluoren-9-yl)methoxy)carbonyl)cyclohexylglycine
• 英文别名: Fmoc-Chg-OH；Fmoc-L-Chg-OH；(2S)-2-cyclohexyl-2-(9H-fluoren-9-ylmethoxycarbonylamino)acetic acid
• CAS: 161321-36-4
• 化学式: C₂₃H₂₅NO₄
• mdl: MFCD00190878
• 分子量: 379.456
• InChiKey: BWQQGHPODCJZDB-NRFANRHFSA-N

物化性质

• 熔点：
  183 °C
• 沸点：
  602.9±38.0 °C(Predicted)
• 密度：
  1.238
• 溶解度：
  溶于氯仿、二氯甲烷、乙酸乙酯、DMSO、丙酮等。

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.391
• 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：
  2922509090
• 危险类别：
  IRRITANT
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: Fmoc-Chg-OH
Synonyms: Fmoc-L-cyclohexylglycine

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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-Chg-OH
CAS number: 161321-36-4

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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.
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
Appearance: Not specified
Boiling point: No data
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C23H25NO4
Molecular weight: 379.5

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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

制备方法与用途

简介

芴甲氧羰酰基环己基甘氨酸可用来合成具有特定结构的环肽抗生素。这些化合物通过抑制脂蛋白信号肽酶II (LspA) 起作用，而 LspA 是细菌中脂蛋白翻译后加工的关键酶。

用途

芴甲氧羰酰基环己基甘氨酸作为一种医药中间体，已报道可用于制备环肽抗生素和IAP抑制剂。

反应信息

• 作为反应物：
  描述：

  芴甲氧羰酰基环己基甘氨酸 在 三乙基硅烷 、 4-甲基苯磺酸吡啶 作用下， 以 氯仿 、 甲苯 为溶剂， 反应 20.0h， 生成 (S)-cyclohexyl[(9H-fluoren-9-ylmethoxycarbonyl)methylamino]acetic acid
  参考文献：
  名称：

  真菌双加氧酶AsqJ是混杂的且是双峰的：喹诺酮类与喹唑啉酮类的底物定向形成

  摘要：

  先前的研究表明，Fe II /α-酮戊二酸依赖性双加氧酶AsqJ诱导构巢曲霉在viridicatin生物合成中的骨架重排，从苯并[1,4]二氮杂-2,5-二酮底物生成喹诺酮骨架。我们报告说，仅通过改变苯并二氮杂二酮底物中的取代基，AsqJ即可催化另外的，完全不同的反应。通过底物筛选，功能探针的应用和计算分析来建立这种新机制。AsqJ消费税H 2由合适的苯并[1,4]二氮杂-2-5,5-二酮底物的杂环结构生成CO，生成喹唑啉酮。这种新颖的AsqJ催化途径由复杂底物中的单个取代基控制。AsqJ的这种独特的底物定向反应性可实现喹诺酮或喹唑啉酮的靶向生物催化生成，喹诺酮或喹唑啉酮是两种具有特殊生物医学相关性的生物碱框架。

  DOI：

  10.1002/anie.202017086
• 作为产物：
  描述：

  氯甲酸-9-芴基甲酯 、 L-环己基甘氨酸 在 sodium carbonate 作用下， 以 水 、 1,4-二氧六环 为溶剂， 反应 8.0h， 生成 芴甲氧羰酰基环己基甘氨酸
  参考文献：
  名称：

  天然和设计的微管溶素的全合成和生物学评价

  摘要：

  描述了基于 CH 激活策略的 N(14)-去乙酰氧基微管溶素 H (Tb1) 的简化全合成和 pretubulysin D (PTb-D43) 的短全合成。还报告了所开发的合成策略和技术在合成一系列微管溶素类似物（Tb2-Tb41 和 PTb-D42）中的应用。针对一系列癌细胞的合成化合物的生物学评估揭示了许多新的类似物（例如，Tb14），其中一些对某些细胞系具有特殊的效力[例如，Tb32 对 MES SA（子宫肉瘤）细胞系的 IC50 = 12 pM和 2 pM 针对 HEK 293T（人胚胎肾）细胞系]，以及一组有价值的构效关系。

  DOI：

  10.1021/jacs.5b12557

文献信息

• Design and synthesis of peptide conjugates of phosphoramide mustard as prodrugs activated by prostate-specific antigen
  作者：Xinghua Wu、Longqin Hu

  DOI：10.1016/j.bmc.2016.04.035

  日期：2016.6

  stability of the conjugates while the position of substitution affected differently the self-immolative process of conjugates upon proteolysis. Introduction of a fluorine at ortho position to benzylic phosphoramide as in 1b results in better stability of the conjugate prior to activation while maintaining its antiproliferative activity upon activation by PSA. The conjugate 1b with 2-fluoro substitution was

  设计并合成了一系列Glutaryl-Hyp-Ala-Ser-Chg-Gln-4-氨基苄基磷酰胺芥末共轭物（1a – e），作为PSA在前列腺癌细胞中进行位点特异性激活的潜在前药。发现所有缀合物都是PSA的底物，在Gln和对氨基苄基（PAB）接头之间发生裂解。对这些结合物的结构-活性关系研究表明，在PAB接头的苯环上引入吸电子的氟均匀地改善了结合物的化学稳定性，而取代位置对结合物的自焚过程产生了不同的影响。蛋白水解。在邻位引入氟如在1b中对苄基磷酰胺的位置导致缀合物在活化之前具有更好的稳定性，同时在被PSA活化时保持其抗增殖活性。具有2-氟取代基的缀合物1b被确定为在前列腺癌靶向前药开发中进行进一步评估和优化的有前途的先导。
• Discovery of a Novel Class of Dimeric Smac Mimetics as Potent IAP Antagonists Resulting in a Clinical Candidate for the Treatment of Cancer (AZD5582)
  作者：Edward J. Hennessy、Ammar Adam、Brian M. Aquila、Lillian M. Castriotta、Donald Cook、Maureen Hattersley、Alexander W. Hird、Christopher Huntington、Victor M. Kamhi、Naomi M. Laing、Danyang Li、Terry MacIntyre、Charles A. Omer、Vibha Oza、Troy Patterson、Galina Repik、Michael T. Rooney、Jamal C. Saeh、Li Sha、Melissa M. Vasbinder、Haiyun Wang、David Whitston

  DOI：10.1021/jm401075x

  日期：2013.12.27

  of dimeric compounds based on the AVPI motif of Smac were designed and prepared as antagonists of the inhibitor of apoptosis proteins (IAPs). Optimization of cellular potency, physical properties, and pharmacokinetic parameters led to the identification of compound 14 (AZD5582), which binds potently to the BIR3 domains of cIAP1, cIAP2, and XIAP (IC50 = 15, 21, and 15 nM, respectively). This compound

  设计并制备了一系列基于Smac的AVPI基序的二聚体化合物，作为凋亡蛋白抑制剂（IAPs）的拮抗剂。细胞效能，物理性质和药代动力学参数的优化导致化合物14（AZD5582）的鉴定，该化合物与cIAP1，cIAP2和XIAP的BIR3域有效结合（IC 50分别为15、21和15 nM）。 。该化合物在体外以亚纳摩尔浓度引起cIAP1降解并诱导MDA-MB-231乳腺癌细胞系凋亡。当对带有MDA-MB-231异种移植的小鼠静脉内给药时，14导致在肿瘤细胞内cIAP1降解和caspase-3裂解，并在每周两次服用3.0 mg / kg的剂量后引起实质性的肿瘤消退。在所检查的200多种癌细胞系中，只有一小部分具有14种抗增殖作用，这与其他已发表的IAP抑制剂一致。由于其体外和体内特性，有14种药物被提名为临床开发的候选药物。
• Design, Synthesis, and Biological Evaluation of Imidazopyrazinone Derivatives as Antagonists of <scp>Inhibitor of Apoptosis Proteins</scp> (IAPs)
  作者：Jisook Kim、Inhwan Bae、Jiyoung Song、Younghoon Kim、Younggil Ahn、Hyun‐Ju Park、Ha Hyung Kim、Dae Kyong Kim

  DOI：10.1002/bkcs.12271

  日期：2021.6

  proteins are overexpressed in many cancers and implicated in tumor growth, so the development of antagonist that disrupts with the binding of IAP to their partner protein is a promising therapeutic strategy. In an effort to increase cellular activity and improve favorable drug-like properties, we newly designed and synthesized monovalent analogues based on imidazopyrazinone structure of 9. Optimization

  凋亡抑制剂 (IAP) 蛋白在许多癌症中过度表达并与肿瘤生长有关，因此开发可破坏 IAP 与其伙伴蛋白结合的拮抗剂是一种很有前景的治疗策略。为了增加细胞活性并改善有利的类药物特性，我们新设计并合成了基于9咪唑并吡嗪酮结构的单价类似物。细胞效力的优化导致17的鉴定，这表 明亚微摩尔活性 (GI 50 = 234 nM) 和 Caspase-3 激活（6.3 倍）在 MDA-MB-231 乳腺癌细胞中增加。这些发现清楚地表明了17 作为开发有效抗癌治疗的有前途的单价拮抗剂。
• Combinatorial Solid-Phase Synthesis and Biological Evaluation of Cyclodepsipeptide Destruxin B as a Negative Regulator for Osteoclast Morphology
  作者：Hiroshi Sato、Masahito Yoshida、Hayato Murase、Hiroshi Nakagawa、Takayuki Doi

  DOI：10.1021/acscombsci.6b00076

  日期：2016.9.12

  Combinatorial synthesis and biological evaluation of cyclodepsipeptide destruxin B have been achieved. The cyclization precursors were prepared by solid-phase peptide synthesis via a split and pool method utilizing SynPhase lanterns with colored tags and cogs, followed by cleavage from the polymer-support. Macrolactonization utilizing MNBA-DMAPO in solution-phase was successfully performed in parallel to afford

  环二肽destruxin B的组合合成和生物学评估已实现。环化前体是通过固相肽合成，使用具有彩色标签和嵌齿轮的SynPhase提灯，通过分体和合并方法制备的，然后从聚合物载体上裂解下来的。在溶液相中成功并行利用MNBA-DMAPO进行了大环内酯化，以中等至良好的收率提供了所需的64元destruxin类似物。合成类似物的生物学评估表明，构件A的MeAla残基需要诱导破骨细胞样多核细胞（OCL）的所需形态变化，并在R 4处引入取代基 形态可容忍脯氨酸部分的位置，并且可以使破骨细胞中用于靶标识别的分子探针的制备成为可能。
• Arylalkanoyl derivatives, processes for their preparation, their use and pharmaceutical compositions containing them
  申请人：Aventis Pharma Deutschland GmbH

  公开号：EP1022268A1

  公开（公告）日：2000-07-26

  The present invention relates to new compounds for the inhibition of blood clotting proteins, and more particularly, to arylalkanoyl derivatives of the formula I, wherein R(1), R(2), R(3), R(4), R(5), R(6a) and R(6b) have the meanings indicated in the claims. The compounds of formula I are inhibitors of the blood clotting enzyme factor Xa. The invention also relates to processes for the preparation of the compounds of formula I, to methods of inhibiting factor Xa activity and of inhibiting blood clotting, to the use of the compounds of formula I in the treatment and prophylaxis of diseases, which can be treated or prevented by the inhibition of factor Xa activity such as thromboembolic diseases, to and the use of the compounds of formula I in the preparation of medicaments to be applied in such diseases. The invention further relates to compositions containing a compound of formula I in admixture or otherwise in association with an inert carrier, in particular pharmaceutical compositions containing a compound of formula I together with pharmaceutically acceptable carrier substances and auxiliary substances.

  本发明涉及用于抑制血液凝固蛋白的新化合物，更具体地，是指式I的芳烷酰衍生物， 其中R(1)、R(2)、R(3)、R(4)、R(5)、R(6a)和R(6b)的含义如权利要求中所示。式I的化合物是血液凝固酶因子Xa的抑制剂。本发明还涉及制备式I化合物的方法，抑制因子Xa活性和血液凝固的方法，使用式I化合物治疗和预防可以通过抑制因子Xa活性来治疗或预防的疾病，如血栓栓塞性疾病，以及使用式I化合物制备用于治疗上述疾病的药物。本发明还涉及包含式I化合物的组合物，与惰性载体混合或以其他方式相关联，尤其是包含式I化合物的药物组合物，以及药用可接受的载体物质和辅助物质。