4-(4-氯苯基)-2,4-二氧代丁酸乙酯 | 5814-38-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 4-(4-氯苯基)-2,4-二氧代丁酸乙酯
• 中文别名: 乙基4-氯-A,G-二氧代-苯丁酸酯；4-氯-A,G-二氧代-苯丁酸乙酯；乙基4-(4-氯苯基)-2,4-二氧代丁酸；2-氧代-3-[3-氯苯甲酰]丙酸,乙酯
• 英文名称: ethyl 4-chlorobenzoylpyruvate
• 英文别名: ethyl 4-(4-chlorophenyl)-2,4-dioxobutanoate
• CAS: 5814-38-0
• 化学式: C₁₂H₁₁ClO₄
• mdl: MFCD01935972
• 分子量: 254.67
• InChiKey: BDFNRYGGOPNIAG-UHFFFAOYSA-N

物化性质

• 熔点：
  61-62.5 °C (decomp)
• 沸点：
  392.8±22.0 °C(Predicted)
• 密度：
  1.276±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  60.4
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2918300090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319
• 储存条件：
  室温和干燥环境中使用。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: Ethyl 4-(4-chlorophenyl)-2,4-dioxobutanoate
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: Ethyl 4-(4-chlorophenyl)-2,4-dioxobutanoate
CAS number: 5814-38-0

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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: C12H11ClO4
Molecular weight: 254.7

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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, hydrogen chloride.

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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：

  4-(4-氯苯基)-2,4-二氧代丁酸乙酯 在 manganese(IV) oxide 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 5-(4-Chlorophenyl)-2-phenylpyrazole-3-carbaldehyde
  参考文献：
  名称：

  La（OTf）3催化一锅法合成吡唑系咪唑并[1,2-a]嗪衍生物及其发光性能

  摘要：

  通过La（OTf）3催化的吡唑甲醛单组分多组分组装，已实现了简便高效的方案，用于多样性导向的高荧光吡唑C-3（5）束缚的咪唑并[1,2- a ]嗪的合成。，2-氨基嗪和异腈。本方案具有几个优点，例如在一个步骤中形成多个键，催化剂用量低，反应时间短，可观的原子经济性，良好的官能团耐受性，可扩展性和易于执行的反应条件。吡唑基咪唑并[1,2的光学性质一个]吖嗪进行了研究，并且它们表现出优异的荧光量子产率（Φ ˚F高达83％）。

  DOI：

  10.1039/c9nj05426j
• 作为产物：
  描述：

  草酸二乙酯 在 sodium hydride 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 17.5h， 以77%的产率得到4-(4-氯苯基)-2,4-二氧代丁酸乙酯
  参考文献：
  名称：

  PYRAZOLE DERIVATIVE

  摘要：

  公开号：

  EP1591443B1

文献信息

• Discovery of 1,5-Diphenylpyrazole-3-Carboxamide Derivatives as Potent, Reversible, and Selective Monoacylglycerol Lipase (MAGL) Inhibitors
  作者：Mojgan Aghazadeh Tabrizi、Pier Giovanni Baraldi、Stefania Baraldi、Emanuela Ruggiero、Lucia De Stefano、Flavio Rizzolio、Lorenzo Di Cesare Mannelli、Carla Ghelardini、Andrea Chicca、Margherita Lapillo、Jürg Gertsch、Clementina Manera、Marco Macchia、Adriano Martinelli、Carlotta Granchi、Filippo Minutolo、Tiziano Tuccinardi

  DOI：10.1021/acs.jmedchem.7b01845

  日期：2018.2.8

  compound 26 showed to be a potent MAGL inhibitor (IC50 = 0.51 μM, Ki = 412 nM) with a good selectivity versus fatty acid amide hydrolase (FAAH), α/β-hydrolase domain-containing 6 (ABHD6), and 12 (ABHD12). Interestingly, this compound also possesses antiproliferative activities against two different cancer cell lines and relieves the neuropathic hypersensitivity induced in vivo by oxaliplatin.

  单酰基甘油脂酶（MAGL）是一种丝氨酸水解酶，在内源性大麻素神经递质2-花生四烯酸甘油酯的降解中起重要作用，这与许多生理过程有关。除了可能将MAGL抑制剂用作抗炎药，抗伤害感受药和抗癌药外，由于不可逆地抑制该酶所引起的不良作用，它们的应用也遇到了障碍。可逆的MAGL抑制剂的可能用途直到最近才被研究，主要是由于缺乏具有有效的可逆抑制活性的已知化合物。在这项工作中，我们报告了一系列新的可逆MAGL抑制剂。其中，化合物26被证明是有效的MAGL抑制剂（IC 50 = 0.51μM ，与脂肪酸酰胺水解酶（FAAH），含α/β水解酶结构域的6（ABHD6）和12（ABHD12）相比，K i = 412 nM）具有良好的选择性。有趣的是，该化合物还具有针对两种不同癌细胞系的抗增殖活性，并减轻了奥沙利铂在体内引起的神经性超敏反应。
• Synthesis and cellular bioactivities of novel isoxazole derivatives incorporating an arylpiperazine moiety as anticancer agents
  作者：Burcu Çalışkan、Esra Sinoplu、Kübra İbiş、Ece Akhan Güzelcan、Rengül Çetin Atalay、Erden Banoglu

  DOI：10.1080/14756366.2018.1504041

  日期：2018.1.1

  In our endeavour towards the development of effective anticancer therapeutics, a novel series of isoxazole-piperazine hybrids were synthesized and evaluated for their cytotoxic activities against human liver (Huh7 and Mahlavu) and breast (MCF-7) cancer cell lines. Within series, compounds 5l-o showed the most potent cytotoxicity on all cell lines with IC50 values in the range of 0.3-3.7 μM. To explore

  在我们努力开发有效的抗癌疗法的过程中，合成了一系列新的异恶唑-哌嗪杂种，并评估了它们对人肝（Huh7和Mahlavu）和乳腺癌（MCF-7）癌细胞系的细胞毒活性。在系列中，化合物5l-o在所有细胞系中显示出最强的细胞毒性，IC50值在0.3-3.7μM的范围内。为了探究观察到的活性的基本机制，对肝癌细胞中5m和5o进行了进一步的生物学研究。我们已经证明5m和5o在足够的PTEN Huh7和PTEN不足的Mahlavu人肝癌细胞中诱导氧化应激，导致细胞凋亡和细胞周期停滞在不同阶段。
• Fragment-Based Lead Generation of 5-Phenyl-1H-pyrazole-3-carboxamide Derivatives as Leads for Potent Factor Xia Inhibitors
  作者：Qunchao Wei、Zhichao Zheng、Shijun Zhang、Xuemin Zheng、Fancui Meng、Jing Yuan、Yongnan Xu、Changjiang Huang

  DOI：10.3390/molecules23082002

  日期：——

  FXIa is suggested as a major target for anticoagulant drug discovery because of reduced risk of bleeding. In this paper, we defined 5-phenyl-1H-pyrazole-3-carboxylic acid derivatives as privileged fragments for FXIa inhibitors’ lead discovery. After replacing the (E)-3-(5-chloro-2-(1H-tetrazol-1-yl)phenyl)acrylamide moiety in compound 3 with 5-(3-chlorophenyl)-1H-pyrazole-3-carboxamide, we traveled from FXIa inhibitor3 to a scaffold that fused the privileged fragments into a pharmacophore for FXIa inhibitors. Subsequently, we synthesized and assessed the FXIa inhibitory potency of a series of 5-phenyl-1H-pyrazole-3-carboxamide derivatives with different P1, P1′ and P2′moiety. Finally, the SAR of them was systematically investigated to afford the lead compound 7za (FXIa Ki = 90.37 nM, 1.5× aPTT in rabbit plasma = 43.33μM) which exhibited good in vitro inhibitory potency against FXIa and excellent in vitro coagulation activities. Furthermore, the binding mode of 7za with FXIa was studied and the results suggest that the 2-methylcyclopropanecarboxamide group of 7za makes 2 direct hydrogen bonds with Tyr58B and Thr35 in the FXIa backbone, making 7za binds to FXIa in a highly efficient manner.

  FXIa被认为是抗凝药物发现的主要靶点，因为减少了出血风险。在这篇论文中，我们将5-苯基-1H-吡唑-3-羧酸衍生物定义为FXIa抑制剂的引物片段，用于引物发现。在将化合物3中的(E)-3-(5-氯-2-(1H-四唑-1-基)苯基)丙烯酰胺基团替换为5-(3-氯苯基)-1H-吡唑-3-羧酰胺后，我们从FXIa抑制剂3转变为将引物片段融合成FXIa抑制剂的药效团的支架。随后，我们合成并评估了一系列具有不同P1、P1'和P2'基团的5-苯基-1H-吡唑-3-羧酰胺衍生物的FXIa抑制活性。最后，对它们的结构活性关系进行了系统研究，得到了引物化合物7za（FXIa Ki = 90.37 nM，在兔血浆中1.5× aPTT = 43.33μM），该化合物表现出良好的体外抑制FXIa活性和优秀的体外凝血活性。此外，研究了7za与FXIa的结合方式，结果表明7za的2-甲基环丙烷甲酰胺基团与FXIa骨架中的Tyr58B和Thr35直接形成两个氢键，使7za以高效的方式结合到FXIa上。
• Development of novel bis-pyrazole derivatives as antitumor agents with potent apoptosis induction effects and DNA damage
  作者：Hong Dai、Shushan Ge、Jing Guo、Shi Chen、Meiling Huang、Jiaying Yang、Siyu Sun、Yong Ling、Yujun Shi

  DOI：10.1016/j.ejmech.2017.11.098

  日期：2018.1

  A series of bis-pyrazole derivatives were designed and synthesized, and their antitumor effects in vitro and in vivo were investigated. Several compounds displayed good antiproliferative activity with IC50 values in low-micromolar range against three human cancer cell lines in vitro, superior to 5-FU. The most potent compound 10M selectively inhibited human hepatocellular carcinoma cells but not non-tumor

  一系列双-吡唑衍生物的设计和合成，并且它们的抗肿瘤作用在体外和体内进行了研究。几种化合物在体外对三种人类癌细胞系均表现出良好的抗增殖活性，其IC 50值在低微摩尔范围内，优于5-FU。最有效的化合物10M在体外选择性抑制人肝癌细胞，但不抑制非肿瘤肝细胞增殖，并通过以浓度依赖性方式裂解PARP和caspase-3来显着触发SMMC-7721细胞凋亡。进一步的研究表明，强效活性对细胞生长具有抑制和凋亡诱导作用。10M与DNA损伤和p53信号通路的激活有关。此外，10M表现出对小鼠的低急性毒性，并且在体内对肝癌肿瘤具有显着的生长抑制作用。
• Design, synthesis and structure-based optimization of novel isoxazole-containing benzamide derivatives as FtsZ modulators
  作者：Fangchao Bi、Di Song、Nan Zhang、Zhiyang Liu、Xinjie Gu、Chaoyu Hu、Xiaokang Cai、Henrietta Venter、Shutao Ma

  DOI：10.1016/j.ejmech.2018.09.053

  日期：2018.11

  becoming a prevalent threat to public health, and new antibacterial agents with novel mechanisms of action hence are in an urgent need. Utilizing computational docking method and structure-based optimization strategy, we rationally designed and synthesized two series of isoxazol-3-yl- and isoxazol-5-yl-containing benzamide derivatives that targeted the bacterial cell division protein FtsZ. Evaluation of their

  临床上重要的细菌病原体中的抗生素耐药性正成为对公共卫生的普遍威胁，因此迫切需要具有新颖作用机制的新型抗菌剂。利用计算对接方法和基于结构的优化策略，我们合理地设计和合成了针对细菌细胞分裂蛋白FtsZ的两个系列的含异恶唑-3-基和异恶唑-5-基的苯甲酰胺衍生物。评估它们对一组革兰氏阳性和阴性病原体的活性表明，具有异恶唑-5-基的化合物B14和B16对包括耐甲氧西林的金黄色葡萄球菌在内的各种测试菌株均显示出强大的抗菌活性。和耐青霉素的金黄色葡萄球菌。进一步的分子生物学研究和对接分析证明，该化合物可作为有效抑制剂，通过刺激机制改变FtsZ自聚合动力学，最终终止细胞分裂并导致细胞死亡。综上所述，这些结果可能暗示了开发新型靶向FtsZ的杀菌剂的有希望的化学型。