NSC73306 | 79560-74-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: NSC73306
• 英文别名: N-(4’-methoxyphenyl)-2-(2-oxoindoline-3-ylidene)hydrazinecarbothioamide；1-isatin-4-(4'-methoxyphenyl)thiosemicarbazone；1-(4-methoxyphenyl)-3-[(2-oxoindol-3-yl)amino]thiourea
• CAS: 79560-74-0
• 化学式: C₁₆H₁₄N₄O₂S
• 分子量: 326.379
• InChiKey: FMJRZOAMRUEUOG-UHFFFAOYSA-N

物化性质

• 熔点：
  240 °C(Solv: ethanol (64-17-5))
• 密度：
  1.38±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO: 10mg/mL, clear

计算性质

• 辛醇/水分配系数(LogP)：
  2.34
• 重原子数：
  23.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  74.75
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  N-甲基哌啶 、 NSC73306 在 聚合甲醛 作用下， 以 乙醇 为溶剂， 反应 0.17h， 以62%的产率得到N-(4-methoxyphenyl)-2-(2-oxo-1-(piperidin-1-ylmethyl)indolin-3-ylidene)hydrazine-1-carbothioamide
  参考文献：
  名称：

  潜在的生物活性剂，XXXII。一些3-(Arylthiosemicarbazono)-2-indolinones的合成和抗病毒活性

  摘要：

  已经合成了一系列 3- (芳基氨基硫代) -2- 吲哚酮 1, 1- 甲基 - 3- (芳基氨基硫代) -2- 吲哚啉酮 2 和 1- (氨基甲基) -3- (芳基氨基硫代) -2- 吲哚酮 3。筛选了所有化合物在体外和体内对 Sunnhemp 玫瑰花结病毒 (SRV) 的抗病毒活性。十二种化合物显示出显着的抗病毒活性。

  DOI：

  10.1002/ardp.19813141105
• 作为产物：
  描述：

  4-甲氧基苯基 异硫氰酸酯 在 盐酸 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 生成 NSC73306
  参考文献：
  名称：

  Pape, Veronika F.S.; Tóth, Szilárd; Füredi, András, European Journal of Medicinal Chemistry, 2016, vol. 117, p. 335 - 354

  摘要：

  DOI：

文献信息

• Functionalized Oxoindolin Hydrazine Carbothioamide Derivatives as Highly Potent Inhibitors of Nucleoside Triphosphate Diphosphohydrolases
  作者：Saira Afzal、Mariya al-Rashida、Abdul Hameed、Julie Pelletier、Jean Sévigny、Jamshed Iqbal

  DOI：10.3389/fphar.2020.585876

  日期：——

  pathophysiological functions of these enzymes are not fully understood due to lack of potent and selective NTPDase inhibitors. Herein, a series of oxoindolin hydrazine carbothioamide derivatives is synthesized and screened for NTPDase inhibitory activity. Four compounds were identified as selective inhibitors of h-NTPDase1 having IC50 values in lower micromolar range, these include compounds 8b (IC50 = 0.29 ± 0

  外核苷三磷酸二磷酸二氢水解酶（NTPDases）是一种外酶，在三磷酸核苷和二磷酸核苷水解为单磷酸核苷中起重要作用。NTPDase1，-2，-3和-8是此酶家族的膜结合成员，负责调节细胞外环境中核苷酸的水平。但是，由于缺乏有效的和选择性的NTPDase抑制剂，这些酶的病理生理功能尚不完全清楚。本文中，合成了一系列的氧吲哚肼肼碳硫酰胺衍生物，并筛选了其对NTPDase的抑制活性。四种化合物被确定为的选择性抑制剂H-NTPDase1具有较低的微摩尔范围的IC 50值，包括化合物8b（IC 50 = 0.29±0.02 µM），8e（IC 50 = 0.15±0.009 µM），8楼（IC 50 = 0.24±0.01 µM）和8升（IC 50 = 0.30±0.03 µM）。同样，复合8k（IC 50 = 0.16±0.01 µM）被发现具有选择性H-NTPDase2抑制剂。的情况下H-NTPDase3，最有效的抑制剂是化合物
• [EN] THIOSEMICARBAZONES WITH MDR1 - INVERSE ACTIVITY<br/>[FR] THIOSEMICARBAZONES À ACTIVITÉ ANTI-MDR1
  申请人：US HEALTH

  公开号：WO2012033601A1

  公开（公告）日：2012-03-15

  Disclosed herein are drug compounds that have MDR-inverse activity and thus are effective against multidrug-resistant cells. Exemplary compounds disclosed herein have the structure;Formula (I). Examples of the disclosed compounds have been found to have, inter alia, efficacy in directly treating multidrug resistant cells, rendering multidrug resistant cells susceptible to other chemotherapeutics and in some instances reversing multidrug resistance.

  本文披露了具有MDR逆转活性的药物化合物，因此对多药耐药细胞有效。本文披露的示例化合物具有下列结构；公式（I）。已发现披露的化合物的示例具有直接治疗多药耐药细胞的功效，使多药耐药细胞对其他化疗药物敏感，并在某些情况下逆转多药耐药。
• Synthesis, Activity, and Pharmacophore Development for Isatin-β-thiosemicarbazones with Selective Activity toward Multidrug-Resistant Cells
  作者：Matthew D. Hall、Noeris K. Salam、Jennifer L. Hellawell、Henry M. Fales、Caroline B. Kensler、Joseph A. Ludwig、Gergely Szakács、David E. Hibbs、Michael M. Gottesman

  DOI：10.1021/jm800861c

  日期：2009.5.28

  We have recently identified a new class of compounds that selectively kill cells that express P-glycoprotein (P-gp, MDR1), the ATPase efflux pump that confers multidrug resistance on cancer cells. Several isatin-beta-thiosemicarbazones from our initial study have been validated and a range of analogues synthesized and tested. A number demonstrated improved MDR1-selective activity over the lead, NSC73306 (1). Pharmacophores for cytotoxicity and MDR1 selectivity were generated to delineate the structural features required for activity. The MDR1-selective pharmacophore highlights the importance of aromatic/hydrophobic features at the N4 position of the thiosemicarbazone and the reliance on the isatin moiety as key bioisosteric contributors. Additionally, a quantitative structure-activity relationship (QSAR) model that yielded a cross-validated correlation coefficient of 0.85 effectively predicts the cytotoxicity of untested thiosemicarbazones. Together, the models serve as effective approaches for predicting structures with MDR1-selective activity and aid in directing the search for the mechanism of action of 1.
• Oxindole derivatives as inhibitors of TAK1 kinase
  作者：Jeffrey W. Lockman、Matthew D. Reeder、Rosann Robinson、Patricia A. Ormonde、Daniel M. Cimbora、Brandi L. Williams、J. Adam Willardsen

  DOI：10.1016/j.bmcl.2011.01.077

  日期：2011.3

  Several series of oxindole analogues were synthesized and screened for inhibitory activity against transforming growth factor-beta-activating kinase 1 (TAK1). Modifications around several regions of the lead molecules were made, with a distal hydroxyl group in the D region being critical for activity. The most potent compound 10 shows an IC50 of 8.9 nM against TAK1 in a biochemical enzyme assay, with compounds 3 and 6 showing low micromolar cellular inhibition. (C) 2011 Elsevier Ltd. All rights reserved.
• Isatin-β-thiosemicarbazones as potent herpes simplex virus inhibitors
  作者：Iou-Jiun Kang、Li-Wen Wang、Tsu-An Hsu、Andrew Yueh、Chung-Chi Lee、Yen-Chun Lee、Ching-Yin Lee、Yu-Sheng Chao、Shin-Ru Shih、Jyh-Haur Chern

  DOI：10.1016/j.bmcl.2011.02.037

  日期：2011.4

  A series of isatin-beta-thiosemicarbazones have been designed and evaluated for antiviral activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in a plaque reduction assay. Their cytotoxicity was examined using human rhabdomyosarcoma cells (RD cells). Several derivatives of isatin-beta-thiosemicarbazone exhibited significant and selective antiviral activity with low cytotoxicity. It was found that the thiourea group at thiosemicarbazone and the NH functionality at isatin were essential for their anti-herpetic activity. The synthesis and structure-activity relationship studies are presented. (C) 2011 Elsevier Ltd. All rights reserved.