2-氰基-4'-氟乙酰苯胺 | 1735-88-2

• 物质功能分类: 有机原料 - 氨基化合物
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-氰基-4'-氟乙酰苯胺
• 中文别名: 2-氰基-N-(4-氟苯基)-乙酰胺
• 英文名称: 2-cyano-N-[4-(fluoro)phenyl]acetamide
• 英文别名: N-(4-fluorophenyl)-2-cyanoacetamide；2-cyano-N-(4-fluorophenyl)acetamide
• CAS: 1735-88-2
• 化学式: C₉H₇FN₂O
• mdl: MFCD00276110
• 分子量: 178.166
• InChiKey: GZWVZXOFWQGSRB-UHFFFAOYSA-N

物化性质

• 熔点：
  158-160 °C(Solv: methanol (67-56-1))
• 沸点：
  396.8±27.0 °C(Predicted)
• 密度：
  1.304±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.111
• 拓扑面积：
  52.9
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2926909090
• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302
• 储存条件：
  室温且干燥

SDS

Material Safety Data Sheet

---

Section 1. Identification of the substance
Product Name: 2-Cyano-n-(4-fluorophenyl)acetamide
Synonyms:

---

Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

---

Section 3. Composition/information on ingredients.
Ingredient name: 2-Cyano-n-(4-fluorophenyl)acetamide
CAS number: 1735-88-2

---

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.

---

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.

---

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.

---

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:

---

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.

---

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: C9H7FN2O
Molecular weight: 178.2

---

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, hydrogen fluoride.

---

Section 11. Toxicological information
No data.

---

Section 12. Ecological information
No data.

---

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.

---

Section 14. Transportation information
Non-harzardous for air and ground transportation.

---

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.

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  2-氰基-4'-氟乙酰苯胺 在 N-甲基吗啉 、 potassium phosphate 、 dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II) 、 2-氯-4,6-二甲氧基-1,3,5-三嗪 、 二碳酸二叔丁酯 、 硫酸 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 乙醇 、 水 、 乙腈 、 二乙二醇 为溶剂， 反应 41.17h， 生成 N-[3-氟-4-[[1-甲基-6-(1H-吡唑-4-基)-1H-吲唑-5-基]氧基]苯基]-1-(4-氟苯基)-1,2-二氢-6-甲基-2-氧代-3-吡啶甲酰胺
  参考文献：
  名称：

  Route Design and Development of a MET Kinase Inhibitor: A Copper-Catalyzed Preparation of an N1-Methylindazole

  摘要：

  The synthesis of a MET kinase inhibitor in an overall yield of 22% was achieved over eight steps starting with 3-hydroxybenzaldehyde, an improvement from the initial 12-step process with a 5.4% yield. Highlights of the process chemistry design and development are a Cu-catalyzed cyclization to form an important N1-methylindazole ring, a selective nitro reduction in the presence of an aryl bromide, a late-stage Suzuki cross-coupling, and a base-promoted Boc deprotection to form the desired drug candidate.

  DOI：

  10.1021/op400317z
• 作为产物：
  描述：

  氰乙酸 、 4-氟苯胺 在 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 二氯甲烷 为溶剂， 以32%的产率得到2-氰基-4'-氟乙酰苯胺
  参考文献：
  名称：

  共价酶抑制的滥交和选择性：亲电子片段的系统研究。

  摘要：

  共价配体-靶标相互作用提供了显着的药理优势。然而，必须使通常具有亲电性质的反应性基团的脱靶反应性最小化，并且不可逆抑制剂的选择性是至关重要的要求。因此，我们进行了系统的研究，以确定可以用作共价结合配体构建基的几个亲电基团的选择性。六个具有亲电性调节基团的反应性基团与11个非反应性基团结合在一起，形成了一个由72个片段状化合物组成的小型组合库。针对一组11个酶靶标筛选了这些化合物，以评估其选择性以及与蛋白质混杂结合的潜力。分析结果显示，混杂程度比最初预期的要低得多，

  DOI：

  10.1021/jm5006918

文献信息

• 3-FURYL-2-CYANO-2-ACRYLAMIDE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION AND USE THEREOF
  申请人：JENKEM TECHNOLOGY CO., LTD. (BEIJING)

  公开号：US20160272604A1

  公开（公告）日：2016-09-22

  Disclosed are a 3-furyl-2-cyano-2-acrylamide derivative with epidermal growth factor receptor (EGFR) inhibitory activity and pharmaceutical acceptable salt thereof, together with preparation method thereof, pharmaceutical composition comprising the compound, and application of the compound in treating senile dementia (AD). The new compound is shown as formula I, wherein R 1 is selected from the group consisting of H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl and C 3 -C 6 cycloalkyl; R 2 is selected from the group consisting of alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl and heteroaralkyl; X is selected from the group consisting of CH 2 , NH, O and S; m and n are all integers greater than or equal to zero.

  揭示了一种具有表皮生长因子受体（EGFR）抑制活性的3-呋喃基-2-氰基-2-丙烯酰胺衍生物及其药用可接受盐，以及其制备方法，包含该化合物的药物组合物，以及该化合物在治疗老年性痴呆症（AD）中的应用。新化合物的化学式如下，其中R1选自H、C1-C6烷基、C2-C6烯基、C2-C6炔基和C3-C6环烷基组成的群；R2选自烷基、环烷基、烯基、炔基、芳基、杂芳基、芳基烷基和杂芳基烷基组成的群；X选自CH2、NH、O和S组成的群；m和n均为大于或等于零的整数。
• Optimization of 2-Acylaminocycloalkylthiophene Derivatives for Activity against Staphylococcus aureus RnpA
  作者：Michaelle Chojnacki、Xufeng Cao、Daniel P. Flaherty、Paul M. Dunman

  DOI：10.3390/antibiotics10040369

  日期：——

  Staphylococcus aureus is well-recognized to cause debilitating bacterial infections that are difficult to treat due to the emergence of antibiotic resistance. As such, there is a need to develop new antimicrobials for the therapeutic intervention of S. aureus disease. To that end, S. aureus RnpA is an essential enzyme that is hypothesized to participate in two required cellular processes, precursor tRNA (ptRNA) maturation and mRNA degradation. Corresponding high throughput screening campaigns have identified the phenylcarbamoyl cyclic thiopenes as a chemical class of RnpA inhibitors that display promising antibacterial effects by reducing RnpA ptRNA and mRNA degradation activities and low human cell toxicity. Herein, we perform a structure activity relationship study of the chemical scaffold. Results revealed that the cycloalkane ring size and trifluoroacetamide moiety are required for antibacterial activity, whereas modifications of the para and/or meta positions of the pharmacophore’s phenyl group allowed tuning of the scaffold’s antimicrobial performance and RnpA inhibitory activity. The top performing compounds with respect to antimicrobial activity also did not exhibit cytotoxicity to human cell lines at concentrations up to 100 µM, greater than 100-fold the minimum inhibitory concentration (MIC). Focused studies of one analog, RNP0012, which exhibited the most potent antimicrobial and inhibition of cellular RnpA activities revealed that the compound reduced bacterial burden in a murine model of S. aureus disease. Taken together, the results presented are expected to provide an early framework for optimization of next-generation of RnpA inhibitor analogues that may represent progenitors of a new class of antimicrobials.

  金黄色葡萄球菌被广泛认为会引起难以治疗的细菌感染，因为抗生素耐药性的出现。因此，有必要开发新的抗菌药物来治疗金黄色葡萄球菌疾病。为此，金黄色葡萄球菌RnpA是一种必不可少的酶，据推测参与两个必需的细胞过程，前体tRNA（ptRNA）成熟和mRNA降解。相应的高通量筛选活动已经确定苯基氨基环硫烯为一种RnpA抑制剂的化学类，通过降低RnpA ptRNA和mRNA降解活性以及低人类细胞毒性显示出有希望的抗菌效果。在这里，我们进行了化学骨架的结构活性关系研究。结果显示，环烷烃环大小和三氟乙酰胺基团对抗菌活性是必需的，而对药效团苯基的对位和/或间位的修饰允许调节骨架的抗微生物性能和RnpA抑制活性。在抗微生物活性方面表现最佳的化合物在浓度高达100 µM时也没有对人类细胞系表现出细胞毒性，这比最低抑菌浓度（MIC）高出100倍。对一种类似物RNP0012的重点研究显示，该化合物减少了在金黄色葡萄球菌疾病小鼠模型中的细菌负担。综合而言，所呈现的结果预计将为优化下一代RnpA抑制剂类似物的早期框架提供基础，这些类似物可能代表新一类抗菌药物的前体。
• Discovery of 8-Amino-Substituted 2-Phenyl-2,7-Naphthyridinone Derivatives as New c-Kit/VEGFR-2 Kinase Inhibitors
  作者：Haiyan Sun、Linsheng Zhuo、Huan Dong、Wei Huang、Nengfang She

  DOI：10.3390/molecules24244461

  日期：——

  scaffold has been proposed as a novel lead structure of MET inhibitors by our group. To broaden the application of this new scaffold, a series of 8-amino-substituted 2-phenyl-2,7-naphthyridin-1(2H)-one derivatives were designed and synthesized. Preliminary biological screening resulted in the discovery of a new lead of c-Kit and VEGFR-2 kinase inhibitors. Compound 9k exhibited excellent c-Kit inhibitory activity

  我们小组已提出 2,7-萘啶酮支架作为 MET 抑制剂的新型先导结构。为了扩大这种新支架的应用，设计并合成了一系列 8-氨基取代的 2-苯基-2,7-萘啶-1(2H)-one 衍生物。初步生物筛选导致发现了 c-Kit 和 VEGFR-2 激酶抑制剂的新先导。化合物9k表现出优异的c-Kit抑制活性，IC50值为8.5nM，即比化合物3(IC50为329.6nM)强38.8倍。此外，化合物10l 和10r 表现出良好的VEGFR-2 抑制活性，IC50 值分别为56.5 和31.7 nM，即它们比化合物3（IC50 为279.9 nM）强5.0-8.8 倍。分子对接实验进一步深入了解新先导化合物与 c-Kit 和 VEGFR-2 激酶的结合相互作用。在这项研究中，8-氨基取代的 2-苯基-2,7-naphthyridin-1(2H)-one 支架被确定为 c-Kit 和 VEGFR-2 激酶抑制剂的新先导结构。
• [EN] FUSED HETEROCYCLIC DERIVATIVES AND USE THEREOF<br/>[FR] DÉRIVÉS HÉTÉROCYCLIQUES FUSIONNÉS ET LEUR UTILISATION
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2009136663A1

  公开（公告）日：2009-11-12

  The present invention provides a fused heterocyclic derivative having a strong kinase inhibitory activity and use thereof. The present invention relates to a compound represented by the formula wherein each symbol is as defined in the present specification, or a salt thereof.

  本发明提供了一种具有强烈激酶抑制活性的融合杂环衍生物及其用途。本发明涉及本说明书中所定义的符号表示的化合物，或其盐。
• Structure-based design, synthesis and biological evaluation of a newer series of pyrazolo[1,5-a]pyrimidine analogues as potential anti-tubercular agents
  作者：Palmi Modi、Shivani Patel、Mahesh Chhabria

  DOI：10.1016/j.bioorg.2019.02.044

  日期：2019.6

  In-depth study of structure-based drug designing can provide vital leads for the development of novel, clinically active molecules. In this present study, twenty six novel pyrazolo[1,5-a]pyrimidine analogues (6a-6z) were designed using molecular docking studies. The designed molecules were synthesized in good yields. Structural elucidation of the synthesized molecules was carried out using IR, MS,

  对基于结构的药物设计的深入研究可以为新型临床活性分子的开发提供重要线索。在本研究中，使用分子对接研究设计了二十六个新颖的吡唑并[1,5- a ]嘧啶类似物（6a - 6z）。设计的分子以高收率合成。使用IR，MS，1 H NMR和13 C NMR光谱进行合成分子的结构阐明。通过Alamar Blue测定法评价所有合成的化合物对H37Rv菌株的体外抗结核活性。大多数合成的化合物显示出有效的抗结核活性。在所有测试的化合物中6p，6g，6n和6h表现出有希望的抗结核活性。此外，对这些有效化合物进行了MDR-TB，XDR-TB和细胞毒性研究的评估。这些化合物均未显示出有效的细胞毒性。蛋白配体复合物的稳定性通过分子动力学模拟进一步评估了10 ns。所有这些结果表明，合成的化合物可能是进一步开发新的有效抗结核药的潜在线索。