5-氨基-1-(4-氟苯基)-3-甲基-1H-吡唑-3-甲腈 | 51516-82-6

• 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-1-(4-氟苯基)-3-甲基-1H-吡唑-3-甲腈
• 中文别名: 5-氨基-4-氰基-1-(4-氟苯基)-3-甲基吡唑
• 英文名称: 5-amino-1-(4-fluorophenyl)-3-methyl-1H-pyrazole-4-carbonitrile
• 英文别名: 5-amino-1-(4-fluorophenyl)-3-methylpyrazole-4-carbonitrile
• CAS: 51516-82-6
• 化学式: C₁₁H₉FN₄
• 分子量: 216.218
• InChiKey: UOLYBVRDNJTPRJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  16
• 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：
  4

安全信息

• 海关编码：
  2933199090

SDS

Material Safety Data Sheet

---

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

---

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

---

Section 3. Composition/information on ingredients.
Ingredient name: 5-Amino-4-cyano-1-(4-fluorophenyl)-3-methylpyrazole
CAS number: 51516-82-6

---

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, refrigerated.
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: C11H9FN4
Molecular weight: 216.2

---

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：

  5-氨基-1-(4-氟苯基)-3-甲基-1H-吡唑-3-甲腈 在 N,N-二甲基甲酰胺 、 三氯氧磷 作用下， 以 二氯甲烷 、 异丙醇 为溶剂， 反应 32.0h， 生成 1‐(3‐(trifluoromethyl)phenyl)‐3‐{4‐[(1‐(4‐fluorophenyl)‐3‐methyl‐1H‐pyrazolo[3,4‐d]pyrimidin‐4‐yl)amino]phenyl}urea
  参考文献：
  名称：

  新型吡唑并嘧啶脲衍生物：合成、抗增殖活性、VEGFR-2 抑制以及对细胞周期曲线的影响

  摘要：

  设计并合成了一系列新型二芳基脲吡唑并嘧啶衍生物。美国国家癌症研究所评估了所有合成化合物的细胞毒活性。四种化合物（5c、5e、5g 和 5h）在 10 µM 剂量下显示出显着的抗增殖活性，因此在五个浓度下对它们进行了评估。它们显示出有效的广谱抗增殖活性，GI50 值介于 0.553 和 3.80 µM 之间，TGI 值介于 2.17–100 µM 之间。这四种化合物有效抑制血管内皮生长因子受体-2 (VEGFR-2)，IC50 值在纳摩尔范围内。分子对接将其强大的 VEGFR-2 抑制活性归因于它们与 VEGFR-2 活性位点中关键氨基酸的相互作用。他们的流式细胞术分析表明，它们通过减少细胞增殖和诱导细胞周期停滞在 G2/M 期来发挥细胞毒活性。此外，它们诱导 DNA 降解或断裂，证实了细胞凋亡在这些化合物诱导的癌细胞死亡和细胞毒性中的作用。

  DOI：

  10.1002/ardp.201900319
• 作为产物：
  描述：

  4-氟苯肼盐酸盐 、 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92%的产率得到5-氨基-1-(4-氟苯基)-3-甲基-1H-吡唑-3-甲腈
  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

• Synthesis and properties of sildenafil isostere
  作者：Ziqi Su、Qi Zhang、Qieqiang Zhao、Wenyi Liu、Tao Zhao、Huiping Wang、Jiarong Li、Juan Xu

  DOI：10.1002/ardp.202100145

  日期：2021.10

  series of novel pyrazolo[3,4-d]pyrimidin-4-one derivatives were synthesized and evaluated for their anti-phosphodiesterase-5 (PDE-5) activity. A total of 28 compounds, containing alkyl and aryl groups at the 1-N and 3-C positions on the pyrazole ring, and also bearing different alkyl substituents on the piperazine ring were synthesized. Four compounds (4d, 5d, 6d, and 5o) were found to have better

  合成了一系列新型吡唑并[3,4- d ]嘧啶-4-酮衍生物，并评估了它们的抗磷酸二酯酶5 (PDE-5) 活性。共合成了 28 种化合物，它们在吡唑环的 1-N 和 3-C 位含有烷基和芳基，在哌嗪环上也带有不同的烷基取代基。发现四种化合物（4d、5d、6d和5o）对 PDE-5 具有更好的抑制活性（IC 50  < 10 nM）。所有四种最活跃的化合物都在 N1 位包含一个苯环。含有 3,5-二甲基哌嗪基的化合物比其他化合物表现出更好的活性。这些结果表明化合物5o可用作开发新的 PDE-5 抑制剂的先导结构。
• 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。
• An unexpected formation of pyrazolopyrimidines during the attempted to obtain 5-substituted tetrazoles from carbonitriles
  作者：Jéssica Venância Faria、Maurício Silva dos Santos、Percilene Fazolin Vegi、Julio Cesar Borges、Alice M.R. Bernardino

  DOI：10.1016/j.tetlet.2013.08.033

  日期：2013.10

  1H-pyrazolo[3,4-d]pyrimidine derivatives 6a–c from 5-amino-1-aryl-3-methyl-1H-pyrazole-4-carbonitriles 4a–c, instead of 5-(5-amino-1-aryl-3-methyl-1H-pyrazole-4-yl)-1H-tetrazoles 5a–c as desired. In an attempt to obtain these tetrazole derivatives containing the methyl group at C3-position in the pyrazole ring, the amino group in 5-amino-1-(4-methoxyphenyl)-3-methyl-1H-pyrazole-4-carbonitrile 4c was protected

  在该信中，我们描述的新的5-（5-氨基-1-芳基- 1合成H-吡唑-4-基）-1- ħ -tetrazoles 2A - Ç从5-氨基-1-芳基- 1 H ^ -吡唑-4-腈1a – c以及意外的1 H-吡唑并[3,4- d ]嘧啶衍生物6a – c来自5-氨基-1-芳基-3-甲基-1 H-吡唑-4-腈4a – c，而不是5-（5-氨基-1-芳基-3-甲基-1 H-吡唑-4-基）-1 H-四唑5a – c如预期的。为了获得这些在吡唑环的C 3位上含有甲基的四唑衍生物，尝试了5-氨基-1-（4-甲氧基苯基）-3-甲基-1 H-吡唑-4-腈4c中的氨基。通过用氢化钠和二-反应保护叔丁基-二碳酸酯（BOC）。使用类似方法从受保护的化合物7c合成四唑衍生物5c，得到2a – c和6a – c。
• CuO-NPs/TFA: a New Catalytic System to Synthesize a Novel Series of Pyrazole Imines with High Antioxidant Properties
  作者：Hanan Mohamed Fathy Elnagdy、Nishi Gandha Gogoi、Jyotirekha G. Handique、Diganta Sarma

  DOI：10.1007/s12668-021-00888-5

  日期：2021.12

  We report here the synthesis of a novel series of pyrazole analogs involving the condensation reaction between 5-amino-1H-pyrazole-4-carbonitrile derivatives and carbonyl compounds. The reactions proceeded in acidic media, and were catalyzed by copper oxide nanoparticles (CuO- NPs) which were synthesized under green condition. The tea leaves extract served as green reducing agent for the conversion of copper nitrate to CuO-NPs. The developed methodology afforded the desired products up to 90% yields in 6 h. The newly synthesized compounds were tested for antioxidant properties. Out of 15 newly developed pyrazole compounds, 11 showed better antioxidant activity than the standard antioxidant drug Trolox.

  我们在此报告了一系列新型吡唑类似物的合成，这些类似物是通过5-氨基-1H-吡唑-4-碳腈衍生物与羰基化合物的缩合反应得到的。这些反应在酸性介质中进行，并由绿色合成的氧化铜纳米颗粒（CuO-NPs）催化。茶叶提取物作为绿色还原剂，将硝酸铜转化为CuO-NPs。开发的方法学在6小时内提供了高达90%的目标产率。新合成的化合物经过了抗氧化性质的测试。在15种新开发的吡唑化合物中，有11种显示出比标准抗氧化药物Trolox更好的抗氧化活性。
• Novel Glu-based pyrazolo[3,4-d]pyrimidine analogues: design, synthesis and biological evaluation as DHFR and TS dual inhibitors
  作者：Mater Mahnashi、Mohammed Merae Alshahrani、Amer Al Ali、Abdulaziz Asiri、Mahrous A. Abou-Salim

  DOI：10.1080/14756366.2023.2203879

  日期：2023.12.31

  Abstract A novel series of multifunctional pyrazolo[3,4-d]pyrimidine-based glutamate analogs (6a–l and 7a,b) have been designed and synthesized as antifolate anticancer agents. Among the tested compounds, 6i exhibited the most potent anti-proliferative activity towards NSCLC, CNS, Ovarian, Prostate, Colon, Melanoma, Breast, and Renal cancers with good to weak cytostatic activity and non-lethal actions

  摘要 已设计并合成了一系列新型多功能吡唑并[3,4-d]嘧啶基谷氨酸类似物（6a-l和7a,b）作为抗叶酸抗癌剂。在测试的化合物中，6i对非小细胞肺癌、中枢神经系统、卵巢癌、前列腺癌、结肠癌、黑色素瘤、乳腺癌和肾癌表现出最有效的抗增殖活性，具有良好或弱的细胞抑制活性和非致死作用。6i表现出比正常细胞更高的癌症选择性。6i可显着增加癌细胞细胞周期分布过程中S期细胞的积累，具有高效诱导细胞凋亡的作用。结果表明6i可能通过 DHFR 和 TS 酶的双重抑制作用（相应的 IC 50 = 2.41 和 8.88 µM）。6i的对接研究表明，N1-对溴苯基和 C3-甲基参与了大量的疏水相互作用。类药特征推断6i符合辉瑞的验收标准。综合起来，6i可能是一个有前途的原型，可以作为一种有效的抗癌药物进一步优化。