5-Amino-1-(4-methoxy-benzenesulfonyl)-1,2-dihydro-pyrazol-3-one | 240117-39-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-Amino-1-(4-methoxy-benzenesulfonyl)-1,2-dihydro-pyrazol-3-one
• 英文别名: 5-amino-1-(4-methoxybenzenesulfonyl)-1H-pyrazol-3-ol；3-amino-2-(4-methoxyphenyl)sulfonyl-1H-pyrazol-5-one
• CAS: 240117-39-9
• 化学式: C₁₀H₁₁N₃O₄S
• 分子量: 269.281
• InChiKey: SENVTPPWWPBGJU-UHFFFAOYSA-N

物化性质

• 密度：
  1.476±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  110
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,6-二氯苯甲酰氯 、 5-Amino-1-(4-methoxy-benzenesulfonyl)-1,2-dihydro-pyrazol-3-one 在 三乙胺 作用下， 以 氯仿 为溶剂， 生成 5-amino-1-(4-methoxyphenylsulfonyl)-1H-pyrazol-3-yl 2,6-dichlorobenzoate
  参考文献：
  名称：

  Structure–activity relationship and improved hydrolytic stability of pyrazole derivatives that are allosteric inhibitors of West Nile Virus NS2B-NS3 proteinase

  摘要：

  West Nile Virus (WNV) is a potentially deadly mosquito-borne flavivirus which has spread rapidly throughout the world. Currently there is no effective vaccine against flaviviral infections. We previously reported the identification of pyrazole ester derivatives as allosteric inhibitors of WNV NS2B-NS3 proteinase. These compounds degrade rapidly in pH 8 buffer with a half life of 1-2 h. We now report the design, synthesis and in vitro evaluation of pyrazole derivatives that are inhibitors of WNV NS2B-NS3 proteinase with greatly improved stability in the assay medium. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.07.150
• 作为产物：
  描述：

  5-amino-1-(4-methoxyphenylsulfonyl)-1H-pyrazol-3-yl 2,6-difluoro-3-methylbenzoate 以 二甲基亚砜 为溶剂， 生成 5-Amino-1-(4-methoxy-benzenesulfonyl)-1,2-dihydro-pyrazol-3-one
  参考文献：
  名称：

  Structure–activity relationship and improved hydrolytic stability of pyrazole derivatives that are allosteric inhibitors of West Nile Virus NS2B-NS3 proteinase

  摘要：

  West Nile Virus (WNV) is a potentially deadly mosquito-borne flavivirus which has spread rapidly throughout the world. Currently there is no effective vaccine against flaviviral infections. We previously reported the identification of pyrazole ester derivatives as allosteric inhibitors of WNV NS2B-NS3 proteinase. These compounds degrade rapidly in pH 8 buffer with a half life of 1-2 h. We now report the design, synthesis and in vitro evaluation of pyrazole derivatives that are inhibitors of WNV NS2B-NS3 proteinase with greatly improved stability in the assay medium. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.07.150

文献信息

• Novel Synthesis of 5-Amino-1-arylsulfonyl-4-pyrazolin-3-ones as a New Class of N-Sulfonylated Pyrazoles
  作者：Galal H. Elgemeie、Nadia H. Metwally

  DOI：10.1039/a800465j

  日期：——

  A novel synthesis of 5-amino-1-arylsulfonyl-4-pyrazolin-3-ones via intramolecular cyclization of cyanoaceto-N-arylsulfonylhydrazides is reported and the synthetic potential of the method is demonstrated.

  报道了一种通过氰基乙酰-N-芳基磺酰肼的分子内环化合成5-氨基-1-芳基磺酰基-4-吡唑啉-3-酮的新方法，并展示了该方法的合成潜力。
• Identification and In Silico Binding Study of a Highly Potent DENV NS2B-NS3 Covalent Inhibitor
  作者：Xincheng Lin、Jiawei Cheng、Yuming Wu、Yaoliang Zhang、Hailun Jiang、Jian Wang、Xuejun Wang、Maosheng Cheng

  DOI：10.1021/acsmedchemlett.1c00653

  日期：2022.4.14

  target for anti-DENV drug discovery. In the current work, a potent NS2B-NS3 covalent inhibitor 23 (IC50 = 6.0 nM, kinac/Ki = 1581 M–1 s–1) was discovered through the chemical modification of a published covalent inhibitor 1 (IC50 = 500 nM, kinac/Ki = 156.1 M–1 s–1), followed by in vitro assay. Further comprehensive structure–activity relationship analysis through covalent docking and molecular dynamics

  登革热病毒（DENV）是一种节肢动物传播的黄病毒，在过去的几十年里发展迅速，成为世界上分布最广的虫媒病毒。NS2B-NS3 在病毒复制和病毒蛋白成熟中的重要作用使其成为抗 DENV 药物发现的最有希望的靶标。在目前的工作中，通过对已发表的共价抑制剂1 ( IC 50 = 500 nM，k inac / K i = 156.1 M–1 s –1 )，然后进行体外测定。通过共价对接和分子动力学模拟进一步全面的结构-活性关系分析提供了对靶向 NS2B-NS3 的共价抑制剂结合模式的信息理解。
• Identification and characterization of 3-substituted pyrazolyl esters as alternate substrates for cathepsin B: The confounding effects of DTT and cysteine in biological assays
  作者：Michael C. Myers、Andrew D. Napper、Nuzhat Motlekar、Parag P. Shah、Chun-Hao Chiu、Mary Pat Beavers、Scott L. Diamond、Donna M. Huryn、Amos B. Smith

  DOI：10.1016/j.bmcl.2007.06.091

  日期：2007.9

  Substituted pyrazole esters were identified as hits in a high hroughput screen (HTS) of the NIH Molecular Libraries Small Molecule Repository (MLSMR) to identify inhibitors of the enzyme cathepsin B. Members of this class, along with functional group analogs, were synthesized in an effort to define the structural requirements for activity. Analog characterization was hampered by the need to include a reducing agent such as dithiothreitol (DTT) or cysteine in the assay, highlighting the caution required in interpreting biological data gathered in the presence of such nucleophiles. Despite the confounding effects of DTT and cysteine, our studies demonstrate that the pyrazole I acts as alternate substrate for cathepsin B, rather than as an inhibitor. (c) 2007 Elsevier Ltd. All rights reserved.
• Structure–activity relationship and improved hydrolytic stability of pyrazole derivatives that are allosteric inhibitors of West Nile Virus NS2B-NS3 proteinase
  作者：Shyama Sidique、Sergey A. Shiryaev、Boris I. Ratnikov、Ananda Herath、Ying Su、Alex Y. Strongin、Nicholas D.P. Cosford

  DOI：10.1016/j.bmcl.2009.07.150

  日期：2009.10

  West Nile Virus (WNV) is a potentially deadly mosquito-borne flavivirus which has spread rapidly throughout the world. Currently there is no effective vaccine against flaviviral infections. We previously reported the identification of pyrazole ester derivatives as allosteric inhibitors of WNV NS2B-NS3 proteinase. These compounds degrade rapidly in pH 8 buffer with a half life of 1-2 h. We now report the design, synthesis and in vitro evaluation of pyrazole derivatives that are inhibitors of WNV NS2B-NS3 proteinase with greatly improved stability in the assay medium. (C) 2009 Elsevier Ltd. All rights reserved.