1-(4-联苯基)-3,4-二[(2-羟基乙基)硫基]-1H-吡咯-2,5-二酮 | 863886-38-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 1-(4-联苯基)-3,4-二[(2-羟基乙基)硫基]-1H-吡咯-2,5-二酮
• 英文名称: 1-(biphenyl-4-yl)-3,4-bis(2-hydroxyethylthio)-1H-pyrrole-2,5-dione
• 英文别名: PM-20；1-Biphenyl-4-yl-3,4-bis-(2-hydroxy-ethylsulfanyl)-pyrrole-2,5-dione；3,4-Bis(2-hydroxyethylsulfanyl)-1-(4-phenylphenyl)pyrrole-2,5-dione
• CAS: 863886-38-8
• 化学式: C₂₀H₁₉NO₄S₂
• 分子量: 401.507
• InChiKey: RFZCIUONZTUZER-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  128
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• 危险品标志：
  N
• 危险类别码：
  R50/53
• 危险品运输编号：
  UN 3077 9/PG 3

反应信息

• 作为反应物：
  描述：

  1-(4-联苯基)-3,4-二[(2-羟基乙基)硫基]-1H-吡咯-2,5-二酮 、 N-乙酰-L-半胱氨酸 以 phosphate buffer solution 为溶剂， 反应 0.5h， 生成 、
  参考文献：
  名称：

  Development of antiproliferative phenylmaleimides that activate the unfolded protein response

  摘要：

  The current paper presents the synthesis and evaluation of a series of maleimides that were designed to inhibit the Cdc25 phosphatase by alkylation of catalytically essential cysteine residues. Although in HepB3 cell culture assays the analogues did exhibit antiproliferative IC50 values ranging from sub-micromolar to greater than 100 mu M, inhibition of Cdc25 through cysteine alkylation could not be demonstrated. It was also found that analysis using fluorescence activated cell sorting (FACS) following treatment with the most potent analogue (1t) did not provide data consistent with inhibition at one specific point in the cell cycle, as would be expected if Cdc25A were inhibited. Further studies with a subset of analogues resulted in a correlation of antiproliferative potencies with activation of the unfolded protein response (UPR). The UPR is a regulatory pathway that temporarily suspends protein production when misfolding of proteins occurs within the endoplastic reticulum(ER). In addition, ER chaperones that promote proper refolding become up-regulated. If cellular damage cannot be resolved by these mechanisms, then the UPR can initiate apoptosis. The current study indicates that these maleimide analogues lead to UPR activation, which is predictive of the selective antiproliferative activity of the series. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2010.04.057
• 作为产物：
  描述：

  1-(biphenyl-4-yl)-3,4-dibromo-1H-pyrrole-2,5-dione 、 2-巯基乙醇 在 咪唑 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以85.6%的产率得到1-(4-联苯基)-3,4-二[(2-羟基乙基)硫基]-1H-吡咯-2,5-二酮
  参考文献：
  名称：

  Development of antiproliferative phenylmaleimides that activate the unfolded protein response

  摘要：

  The current paper presents the synthesis and evaluation of a series of maleimides that were designed to inhibit the Cdc25 phosphatase by alkylation of catalytically essential cysteine residues. Although in HepB3 cell culture assays the analogues did exhibit antiproliferative IC50 values ranging from sub-micromolar to greater than 100 mu M, inhibition of Cdc25 through cysteine alkylation could not be demonstrated. It was also found that analysis using fluorescence activated cell sorting (FACS) following treatment with the most potent analogue (1t) did not provide data consistent with inhibition at one specific point in the cell cycle, as would be expected if Cdc25A were inhibited. Further studies with a subset of analogues resulted in a correlation of antiproliferative potencies with activation of the unfolded protein response (UPR). The UPR is a regulatory pathway that temporarily suspends protein production when misfolding of proteins occurs within the endoplastic reticulum(ER). In addition, ER chaperones that promote proper refolding become up-regulated. If cellular damage cannot be resolved by these mechanisms, then the UPR can initiate apoptosis. The current study indicates that these maleimide analogues lead to UPR activation, which is predictive of the selective antiproliferative activity of the series. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2010.04.057

文献信息

• Maleiimide anti-tumor phosphatase inhibitors
  申请人：Michejda J. Christopher

  公开号：US20080039518A1

  公开（公告）日：2008-02-14

  The present invention features maleiimide compounds, pharmaceutical compositions of maleiimide compounds and methods of treating a patient suffering from cancer, the method comprising administering to a patient one or more maleiimide compounds of the invention.

  本发明涉及maleiimide化合物、maleiimide化合物的药物组成物以及治疗患有癌症的患者的方法，该方法包括向患者施用本发明中的一个或多个maleiimide化合物。
• CDC25A inhibitor for the treatment of drug resistant cancer or for the prevention of tumor relapse
  申请人：INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE)

  公开号：US10179914B2

  公开（公告）日：2019-01-15

  The present invention concerns a CDC25A phosphatase inhibitor for use in the treatment of a drug resistant cancer and/or in prevention of tumor relapse in a patient suffering or having suffered from cancer.

  本发明涉及一种 CDC25A 磷酸酶抑制剂，用于治疗耐药性癌症和/或预防癌症患者的肿瘤复发。
• MALEIIMIDE ANTI-TUMOR PHOSPHATASE INHIBITORS
  申请人：THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES

  公开号：EP1722781A2

  公开（公告）日：2006-11-22
• CDC25A INHIBITOR FOR THE TREATMENT OF DRUG RESISTANT CANCER OR FOR THE PREVENTION OF TUMOR RELAPSE
  申请人：INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE)

  公开号：US20170247706A1

  公开（公告）日：2017-08-31

  The present invention concerns a CDC25A phosphatase inhibitor for use in the treatment of a drug resistant cancer and/or in prevention of tumor relapse in a patient suffering or having suffered from cancer.
• US7504430B2
  申请人：——

  公开号：US7504430B2

  公开（公告）日：2009-03-17