5-氨基-4-氰基-1-(2,4-二氯苯基)-3-甲基-1H-吡唑 | 58791-83-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 5-氨基-4-氰基-1-(2,4-二氯苯基)-3-甲基-1H-吡唑
• 英文名称: 5-amino-1-(2,4-dichlorophenyl)-3-methyl-1H-pyrazole-4-carbonitrile
• 英文别名: 5-Amino-4-cyano-1-(2,4-dichlorophenyl)-3-methylpyrazol；5-amino-1-(2,4-dichlorophenyl)-3-methylpyrazole-4-carbonitrile
• CAS: 58791-83-6
• 化学式: C₁₁H₈Cl₂N₄
• mdl: MFCD10699683
• 分子量: 267.117
• InChiKey: MYZXVPWAKMKNPD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  67.6
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933199090

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 5-Amino-4-cyano-1-(2,4-dichlorophenyl)-3-methyl-1H-pyrazole
Synonyms: 5-Amino-1-(2,4-dichlorophenyl)-3-methyl-1H-pyrazole-4-carbonitrile

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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: 5-Amino-4-cyano-1-(2,4-dichlorophenyl)-3-methyl-1H-pyrazole
CAS number: 58791-83-6

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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, refrigerated.
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: C11H8Cl2N4
Molecular weight: 267.1

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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 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：

  5-氨基-4-氰基-1-(2,4-二氯苯基)-3-甲基-1H-吡唑 在 sodium azide 、 亚硝酸特丁酯 、 氯化铵 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 5-[1-(2,4-dichlorophenyl)-3-methyl-1H-pyrazol-4-yl]-1H‑tetrazole
  参考文献：
  名称：

  新型四唑化合物及其吡唑-4-腈前体的抗利什曼原虫的合成及活性

  摘要：

  一系列新的5-（1-芳基-3-甲基-1 H-吡唑-4-基）-1 H-四唑衍生物（4a – m）及其前体1-芳基-3-甲基-1 H-吡唑合成-4-腈（3a – m）并作为抗疟药对巴西利什曼原虫和亚马逊利什曼原虫前鞭毛体进行了评价。同时，在RAW 264.7细胞系上评估了这些化合物的细胞毒性。结果表明，在待测化合物中，取代的3-氯苯基（4a）（IC 50/24 h = 15±0.14μM）和3,4-二氯苯基四唑（4d）（IC 50 /24小时= 26±0.09μM）反对的最有力的L. braziliensis前鞭毛体，与参考药物喷他脒，其中提出IC 50  = 13±0.04μM。此外，4a和4d衍生物的细胞毒性低于喷他idine。然而，这些四唑衍生物（4）和吡唑-4-甲腈的前体（3）针对不同每种测试物种的和反对更有效的巴西利什曼原虫比亚马逊利什曼原虫。

  DOI：

  10.1016/j.bmcl.2013.09.062
• 作为产物：
  描述：

  2,4-二氯苯肼盐酸盐 、 2-(1-乙氧基亚乙基)丙二腈 在 sodium acetate 作用下， 以 乙醇 为溶剂， 反应 1.0h， 以73%的产率得到5-氨基-4-氰基-1-(2,4-二氯苯基)-3-甲基-1H-吡唑
  参考文献：
  名称：

  新型四唑化合物及其吡唑-4-腈前体的抗利什曼原虫的合成及活性

  摘要：

  一系列新的5-（1-芳基-3-甲基-1 H-吡唑-4-基）-1 H-四唑衍生物（4a – m）及其前体1-芳基-3-甲基-1 H-吡唑合成-4-腈（3a – m）并作为抗疟药对巴西利什曼原虫和亚马逊利什曼原虫前鞭毛体进行了评价。同时，在RAW 264.7细胞系上评估了这些化合物的细胞毒性。结果表明，在待测化合物中，取代的3-氯苯基（4a）（IC 50/24 h = 15±0.14μM）和3,4-二氯苯基四唑（4d）（IC 50 /24小时= 26±0.09μM）反对的最有力的L. braziliensis前鞭毛体，与参考药物喷他脒，其中提出IC 50  = 13±0.04μM。此外，4a和4d衍生物的细胞毒性低于喷他idine。然而，这些四唑衍生物（4）和吡唑-4-甲腈的前体（3）针对不同每种测试物种的和反对更有效的巴西利什曼原虫比亚马逊利什曼原虫。

  DOI：

  10.1016/j.bmcl.2013.09.062

文献信息

• Pyrazolyl-Tetrazoles and Imidazolyl-Pyrazoles as Potential Anticoagulants and their Integrated Multiplex Analysis Virtual Screening
  作者：André Lourenço、Percilene Vegi、Jéssica Faria、Gustavo Pinto、Maurício dos Santos、Plínio Sathler、Max Saito、Marcos Santana、Tatiana Dutra、Carlos Rodrigues、Robson Monteiro、Alice Bernardino、Helena Castro

  DOI：10.21577/0103-5053.20180150

  日期：——

  ( )This article reports a novel virtual screening algorithm seeking the rational identification of novel lead anticoagulants. Seven 5-(3-methyl-1-aryl-1H-pyrazol-4-yl)-1H-tetrazoles and seven novel 1-aryl-4-(4.5-dihydro-1H-imidazol-2-yl)-3-methyl-1H-pyrazoles were obtained in three steps starting from arylhydrazine hydrochlorides as raw materials in good yields: 50-72% and 50-85%, respectively. All compounds were submitted to an in silico target-base pipeline named integrated multiplex analysis virtual screening (IMA-VS), which comprises the evaluation of their (i) fitting physicochemical properties to the chemical environment of the target enzyme; (ii) active-site homing electrostatic potential to the target enzyme; (iii) structural fitting to the target active site through molecular docking; and (iv) overall absorption, distribution, metabolism, excretion and toxicity (ADMET) profile. After the virtual selection of potential anticoagulant hits, all molecules were synthesized and candidates were evaluated in vitro for their anticoagulant and hemolytic profile. The most promising candidate pointed out by IMA-VS was compound 1-(3',4'-dichlorophenyl)-4-(4,5-dihydro-1H-imidazol-2-yl)-3-methyl -1H-pyrazole that shown to display factor Xa (FXa)-specific inhibitory activity in vitro, acting as an uncompetitive inhibitor with an inhibition constant (Ki) = 61.16 +/- 12.96 mu M, in addition to the lowest hemolytic activity of the series. Further experiments revealed the antithrombotic activity of this compound in an in vivo model of arterial thrombosis induced by FeCl3.

  本文报道了一种新颖的虚拟筛选算法，旨在合理识别新型抗凝血药物先导物。从联胺盐酸盐出发，通过三步合成路线分别以50-72%和50-85%的优良收率获得了7种5-(3-甲基-1-芳基-1H-吡咯并[1,2-b]咪唑-4-基)-1H-四氮唑和7种新型1-芳基-4-(4,5-二氢-1H-咪唑-2-基)-3-甲基-1H-吡咯并[1,2-b]咪唑。所有化合物均提交给一个基于靶点的体外虚拟筛选管道(综合多梯度分析虚拟筛选(IMA-VS))，其中包括对(i)其物理化学性质与靶点酶化学环境的契合性；(ii)靶点酶活性位点的静电势；(iii)通过分子对接对靶点活性位点的结构契合性；以及(iv)整体吸收、分布、代谢、排泄和毒性(ADMET)轮廓的评估。IMA-VS在虚拟筛选出潜在抗凝血药物候选物后,所有分子均被合成,并在体外进行了抗凝活性和溶血活性评价。由IMA-VS指向的最有望候选物1-(3',4'-二氯苯基)-4-(4,5-二氢-1H-咪唑-2-基)-3-甲基吡咯并[1,2-b]咪唑表现出体外对因子Xa(FXa)的特异性抑制活性，作用为一种非竞争性抑制剂，其抑制常数(Ki)为61.16 ± 12.96 µM，同时具有系列中最低的溶血活性。进一步的实验揭示了该化合物在由FeCl3诱导的动脉血栓形成的小鼠模型中的抗血栓活性。
• Vicentini; Poli; Manfrini, Farmaco, Edizione Scientifica, 1987, vol. 42, # 2, p. 133 - 143
  作者：Vicentini、Poli、Manfrini、Guarneri、Giori、Brandolini

  DOI：——

  日期：——
• Synthesis and activity of novel tetrazole compounds and their pyrazole-4-carbonitrile precursors against Leishmania spp
  作者：Jéssica V. Faria、Maurício S. dos Santos、Alice M.R. Bernardino、Klaus M. Becker、Gérzia M.C. Machado、Raquel F. Rodrigues、Marilene M. Canto-Cavalheiro、Leonor L. Leon

  DOI：10.1016/j.bmcl.2013.09.062

  日期：2013.12

  e derivatives (4a–m) and their precursor 1-aryl-3-methyl-1H-pyrazole-4-carbonitriles (3a–m) were synthesized and evaluated as antileishmanials against Leishmania braziliensis and Leishmania amazonensis promastigotes in vitro. In parallel, the cytotoxicity of these compounds was evaluated on the RAW 264.7 cell line. The results showed that among the assayed compounds the substituted 3-chlorophenyl (4a)

  一系列新的5-（1-芳基-3-甲基-1 H-吡唑-4-基）-1 H-四唑衍生物（4a – m）及其前体1-芳基-3-甲基-1 H-吡唑合成-4-腈（3a – m）并作为抗疟药对巴西利什曼原虫和亚马逊利什曼原虫前鞭毛体进行了评价。同时，在RAW 264.7细胞系上评估了这些化合物的细胞毒性。结果表明，在待测化合物中，取代的3-氯苯基（4a）（IC 50/24 h = 15±0.14μM）和3,4-二氯苯基四唑（4d）（IC 50 /24小时= 26±0.09μM）反对的最有力的L. braziliensis前鞭毛体，与参考药物喷他脒，其中提出IC 50  = 13±0.04μM。此外，4a和4d衍生物的细胞毒性低于喷他idine。然而，这些四唑衍生物（4）和吡唑-4-甲腈的前体（3）针对不同每种测试物种的和反对更有效的巴西利什曼原虫比亚马逊利什曼原虫。