3-[3-(4-氟苯基)-1,2,4-恶二唑-5-基]丙酸 | 500025-07-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 3-[3-(4-氟苯基)-1,2,4-恶二唑-5-基]丙酸
• 英文名称: 3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]-propionic acid
• 英文别名: 3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]propanoic acid
• CAS: 500025-07-0
• 化学式: C₁₁H₉FN₂O₃
• mdl: MFCD05130922
• 分子量: 236.202
• InChiKey: BUMRHSFCLPSTJE-UHFFFAOYSA-N

物化性质

• 熔点：
  146-147 °C(Solv: chloroform (67-66-3))
• 沸点：
  426.8±55.0 °C(Predicted)
• 密度：
  1.372±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.181
• 拓扑面积：
  76.2
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2934999090

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 3-[3-(4-Fluorophenyl)-1,2,4-oxadiazol-5-yl]propanoic acid
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: 3-[3-(4-Fluorophenyl)-1,2,4-oxadiazol-5-yl]propanoic acid
CAS number: 500025-07-0

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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: C11H9FN2O3
Molecular weight: 236.2

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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, nitrogen oxides, hydrogen fluoride.

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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：

  3-[3-(4-氟苯基)-1,2,4-恶二唑-5-基]丙酸 在 (1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate 、 diethylaminodifluorosulfinium tetrafluoroborate 、 triethylamine tris(hydrogen fluoride) 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.5h， 生成 N-[9-(2-fluoroethyl)-9H-carbazol-3-yl]-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]propanamide
  参考文献：
  名称：

  Development of fluorinated CB2 receptor agonists for PET studies

  摘要：

  A convergent strategy was followed to modify systematically carbazole based CB2 receptor ligands. The length of the N-(fluoroalkyl) group (n in 7), the length of the alkanamide (m in 7) and the substitution pattern of the phenyl moiety (X and Y in 7) were varied systematically. The highest CB2 affinity was found for the 2-fluoroethyl substituted carbazole derivative 20a (K-i = 5.8 nM) containing the propionamide and the 2-bromo-4-fluorophenyl moiety. According to docking studies 20a fits nicely into the binding pocket of the CB2 receptor, but elongation of the fluoroethyl side chain leads to a different binding mode of the ligands. The high CB2 affinity together with the high selectivity over the CB2 subtype qualifies the fluoroethyl derivative 20a to be developed as a PET tracer. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.09.040
• 作为产物：
  描述：

  对氟苯腈 在 盐酸羟胺 、 碳酸氢钠 作用下， 以 乙醇 、 水 为溶剂， 反应 1.0h， 生成 3-[3-(4-氟苯基)-1,2,4-恶二唑-5-基]丙酸
  参考文献：
  名称：

  第二代 1,2,4-恶二唑衍生物，具有增强的溶解度，可抑制埃及伊蚊的 3-羟基犬尿氨酸转氨酶 (HKT)

  摘要：

  控制埃及伊蚊种群最广泛使用的方法是化学控制方法。它代表了一种通过病媒控制来遏制多种疾病（例如登革热、寨卡、基孔肯雅热、黄热病）的省时且经济有效的方法。因此，为了最大限度地减少杀虫剂抗药性的上升，必须发现与现有化合物具有不同作用方式的新化合物。解毒酶是发现新杀虫剂的一个有吸引力的目标。犬尿氨酸途径是一条重要的代谢途径，它产生化学稳定的黄尿酸，由活性氧和氮物质的前体 3-羟基犬尿氨酸通过 3-羟基犬尿氨酸转氨酶 (HKT) 生物合成。此前，我们通过体外和计算机研究报道了 1,2,4-恶二唑衍生物作为埃及伊蚊和 AeHKT 抑制剂的杀幼剂的有效性。在这里，我们报道了新型 4-[3-(芳基)-1,2,4-恶二唑-5-基]丙酸钠的合成及其同源 HKT 抑制活性。这些新衍生物可作为竞争性抑制剂，IC 50值在 42 至 339 μM 范围内。我们进一步对我们小组先前报道的先前合成的4-[3-(芳基)-1

  DOI：

  10.1039/d0md00305k

文献信息

• A second generation of 1,2,4-oxadiazole derivatives with enhanced solubility for inhibition of 3-hydroxykynurenine transaminase (HKT) from <i>Aedes aegypti</i>
  作者：Larissa G. Maciel、Andrey da S. Barbosa、Edilson B. de Alencar-Filho、Thereza A. Soares、Janaína V. dos Anjos

  DOI：10.1039/d0md00305k

  日期：——

  (HKT). Previously, we have reported the effectiveness of 1,2,4-oxadiazole derivatives acting as larvicides for A. aegypti and AeHKT inhibitors from in vitro and in silico studies. Here, we report the synthesis of new sodium 4-[3-(aryl)-1,2,4-oxadiazol-5-yl] propanoates and the cognate HKT-inhibitory activity. These new derivatives act as competitive inhibitors with IC50 values in the range of 42 to 339

  控制埃及伊蚊种群最广泛使用的方法是化学控制方法。它代表了一种通过病媒控制来遏制多种疾病（例如登革热、寨卡、基孔肯雅热、黄热病）的省时且经济有效的方法。因此，为了最大限度地减少杀虫剂抗药性的上升，必须发现与现有化合物具有不同作用方式的新化合物。解毒酶是发现新杀虫剂的一个有吸引力的目标。犬尿氨酸途径是一条重要的代谢途径，它产生化学稳定的黄尿酸，由活性氧和氮物质的前体 3-羟基犬尿氨酸通过 3-羟基犬尿氨酸转氨酶 (HKT) 生物合成。此前，我们通过体外和计算机研究报道了 1,2,4-恶二唑衍生物作为埃及伊蚊和 AeHKT 抑制剂的杀幼剂的有效性。在这里，我们报道了新型 4-[3-(芳基)-1,2,4-恶二唑-5-基]丙酸钠的合成及其同源 HKT 抑制活性。这些新衍生物可作为竞争性抑制剂，IC 50值在 42 至 339 μM 范围内。我们进一步对我们小组先前报道的先前合成的4-[3-(芳基)-1
• Improved Microwave-Mediated Synthesis of 3-(3-Aryl-1,2,4-oxadiazol-5-yl)propionic Acids and Their Larvicidal and Fungal Growth Inhibitory Properties
  作者：Ricardo Antonio Wanderley Neves Filho、Cec&iacute;lia Aguiar da Silva、Cl&eacute;cia Sipriano Borges da Silva、Vanessa Passos Brustein、Daniela Maria do Amaral Ferraz Navarro、F&aacute;bio Andr&eacute; Brayner dos Santos、Luiz Carlos Alves、Mar&iacute;lia Gabriela dos Santos Cavalcanti、Rajendra Mohan Srivastava、Maria das Gra&ccedil;as Carneiro-Da-Cunha

  DOI：10.1248/cpb.57.819

  日期：——

  The synthesis of 3-(3-aryl-1,2,4-oxadiazol-5-yl)propionic acids from arylamidoximes and succinic anhydride under focused microwave irradiation conditions is described. The new synthetic method furnished the desired products in 2-3 min and good yields. Furthermore, the previously complicated purification procedure has been simplified in a manner which is quick, eco-friendly and cost-effective. Larvicidal

  描述了在聚焦微波辐射条件下由芳基嘧啶和琥珀酸酐合成3-（3-芳基-1,2,4-恶二唑-5-基）丙酸。新的合成方法可在2-3分钟内提供所需的产品，并具有良好的产量。此外，先前复杂的纯化过程已经以快速，环保和成本有效的方式得到简化。使用几种3-（3-芳基-1,2,4-恶二唑-5-基）丙酸进行了杀幼虫的生物测定和真菌生长抑制试验。这些酸对埃及伊蚊的L4幼虫具有很强的杀幼虫活性。结果表明，杀幼虫活性可能与除氟原子以外的苯环对位的吸电子取代基的存在有关。在幼虫生物测定中，1,2,4-恶二唑在虹吸管和肛门乳头的幼虫螺旋瓣中观察到的变化是幼虫死亡的原因。此外，在初步评估中，所有酸均抑制了五种不同类型的真菌（即镰刀镰刀菌，尖孢镰刀菌，念珠形镰刀菌，十二指肠球菌和红曲霉）的真菌生长。这两个活性都首次公开了在丙酸的C-3处连接的1,2,4-恶二唑-5-基环。
• Discovery and Optimization of a Novel Series of <i>N</i>-Arylamide Oxadiazoles as Potent, Highly Selective and Orally Bioavailable Cannabinoid Receptor 2 (CB₂) Agonists
  作者：Yuan Cheng、Brian K. Albrecht、James Brown、John L. Buchanan、William H. Buckner、Erin F. DiMauro、Renee Emkey、Robert T. Fremeau、Jean-Christophe Harmange、Beth J. Hoffman、Liyue Huang、Ming Huang、Josie Han Lee、Fen-Fen Lin、Matthew W. Martin、Hung Q. Nguyen、Vinod F. Patel、Susan A. Tomlinson、Ryan D. White、Xiaoyang Xia、Stephen A. Hitchcock

  DOI：10.1021/jm800463f

  日期：2008.8.1

  describe the discovery of a novel class of oxadiazole derivatives from which potent and selective CB2 agonist leads were developed. Initial hit 7 was identified from a cannabinoid target-biased library generated by virtual screening of sample collections using a pharmacophore model in combination with a series of physicochemical filters. 7 was demonstrated to be a selective CB2 agonist (CB2 EC50 = 93

  CB2受体是止痛药和抗炎药的有吸引力的治疗靶标。在本文中，我们描述了发现一类新的恶二唑衍生物的发现，由此开发了有效的和选择性的CB2激动剂。通过使用药效团模型结合一系列物理化学过滤器对样品集合进行虚拟筛选，从大麻靶偏倚的文库中识别出最初的第7个匹配项。7被证明是选择性CB2激动剂（CB2 EC50 = 93 nM，Emax = 98％，CB1 EC50> 10 microM）。但是，该化合物在大鼠中表现出较差的溶解性和相对较高的清除率，导致口服生物利用度低。在本文中，我们报告了有关提高功效，理化性质和溶解度的7条途径的详细SAR研究。
• Parp inhibitors
  申请人：ICOS Corporation

  公开号：US20040087588A1

  公开（公告）日：2004-05-06

  The present invention provides compounds comprising a bicyclic aryl moiety, such as 2H-phthalazin-1-one or derivatives thereof, compositions comprising the same, and methods for producing and using the same. In particular, the present invention provides compounds of the formula: 1 or a pharmaceutically acceptable salt, a hydrate, a solvate, or a prodrug thereof; where Q 1 , Q 2 and Y are those defined herein.

  本发明提供了包含双环芳基基团的化合物，例如2H-萘嗪-1-酮或其衍生物，以及包含这些化合物的组合物，以及制备和使用这些化合物的方法。特别地，本发明提供了式1的化合物：1或其药学上可接受的盐、水合物、溶剂合物或前药；其中Q1、Q2和Y的定义如本文所述。
• 2H-PHTHALAZIN-1-ONES AND METHODS FOR USE THEREOF
  申请人：ICOS CORPORATION

  公开号：EP1423120A1

  公开（公告）日：2004-06-02