5-amino-1-(3,4-dichlorophenyl)-3-methyl-1H-pyrazole-4-carbonitrile | 58791-84-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-amino-1-(3,4-dichlorophenyl)-3-methyl-1H-pyrazole-4-carbonitrile
• 英文别名: 5-Amino-4-cyano-1-(3,4-dichlorophenyl)-3-methylpyrazol；5-amino-1-(3,4-dichlorophenyl)-3-methylpyrazole-4-carbonitrile
• CAS: 58791-84-7
• 化学式: C₁₁H₈Cl₂N₄
• 分子量: 267.117
• InChiKey: HKNLKJPRTBFITM-UHFFFAOYSA-N

物化性质

• 熔点：
  236-237 °C(Solv: ethanol (64-17-5))
• 沸点：
  466.1±45.0 °C(Predicted)
• 密度：
  1.48±0.1 g/cm3(Predicted)

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

反应信息

• 作为反应物：
  描述：

  5-amino-1-(3,4-dichlorophenyl)-3-methyl-1H-pyrazole-4-carbonitrile 以42%的产率得到
  参考文献：
  名称：

  SOUTHWICK P. L.; DHAWAN B., J. HETEROCYCL. CHEM. , 1975, 12, NO 6, 1199-1205

  摘要：

  DOI：
• 作为产物：
  描述：

  5-Amino-1-(3,4-dichloro-phenyl)-3-methyl-1H-pyrazole-4-carbothioic acid amide 在 双氧水 作用下， 以 吡啶 为溶剂， 生成 6-(3,4-Dichloro-phenyl)-4-methyl-6H-pyrazolo[3,4-c]isothiazol-3-ylamine 、 5-amino-1-(3,4-dichlorophenyl)-3-methyl-1H-pyrazole-4-carbonitrile
  参考文献：
  名称：

  Vicentini; Poli; Manfrini, Farmaco, Edizione Scientifica, 1987, vol. 42, # 2, p. 133 - 143

  摘要：

  DOI：

文献信息

• 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。
• 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：——
• SOUTHWICK P. L.; DHAWAN B., J. HETEROCYCL. CHEM. <JHTC-AD>, 1975, 12, NO 6, 1199-1205
  作者：SOUTHWICK P. L.、 DHAWAN B.

  DOI：——

  日期：——