N-(4-methoxyphenyl)-2-(5-nitro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-1-hydrazinecarbothioamide | 503282-63-1

• 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: N-(4-methoxyphenyl)-2-(5-nitro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-1-hydrazinecarbothioamide
• 英文别名: 1-(5'-nitroisatin)-4-(4'-methoxyphenyl)-3-thiosemicarbazone
• CAS: 503282-63-1
• 化学式: C₁₆H₁₃N₅O₄S
• 分子量: 371.376
• InChiKey: XZCDEJOUGGFBTJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.25
• 重原子数：
  26.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  117.89
• 氢给体数：
  3.0
• 氢受体数：
  6.0

文献信息

• [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。
• Isatin thiosemicarbazones promote honeycomb structure formation in spin-coated polymer films: concentration effect and release studies
  作者：V. García Fernández-Luna、D. Mallinson、P. Alexiou、I. Khadra、A. B. Mullen、M. Pelecanou、M. Sagnou、D. A. Lamprou

  DOI：10.1039/c6ra28163j

  日期：——

  affected by ITSC type and concentration. PMMA films presented a higher density of pores with a smaller pore diameter (280 ± 20 nm) compared to PU films (647 ± 54 nm). A 24 h dissolution study showed a gradual release of ITSC from the PMMA film, in a pH dependent manner, reaching almost completion, while PU showed no detectable release. Overall, PMMA films blended with ITSCs present favourable characteristics

  有序的多孔聚合物膜的形成是目前正在研究的技术之一，因为它具有制造生物医学应用涂层的潜力。针对具有改善的细菌定殖特性的薄膜，通过以下方法形成了聚（甲基丙烯酸甲酯）（PMMA）和聚氨酯（PU）薄膜在不存在或存在四种浓度的不同浓度的Isatin thiosemicarbazone衍生物（ITSC）的情况下，在二氧化硅晶片（SW）基底上进行旋涂法。根据接触角测角法测得的结果，所得膜表现出高疏水性，范围从最小的水接触角值（对于PMMA为84.0°±4.0和对于PU而言为85.0°±0.2）到最大129.3°±2.6和102.1°±1.4，分别添加ITSC之后。原子力显微镜显示聚合物表面粗糙，蜂窝结构受ITSC类型和浓度影响。与PU膜（647±54 nm）相比，PMMA膜的孔密度更高，孔径较小（280±20 nm）。一项24小时的溶出度研究表明，ITSC以pH依赖的方式从PMMA膜中逐渐释放出来，几乎
• 5-Nitroisatin-derived thiosemicarbazones: potential antileishmanial agents
  作者：Humayun Pervez、Nazia Manzoor、Muhammad Yaqub、Khalid Mohammed Khan

  DOI：10.3109/14756366.2013.836641

  日期：2014.10.1

  A series of 29 previously reported N(4)-substituted 5-nitroisatin-3-thiosemicarbazones 2-30 has been screened for leishmanicidal potential. Compounds 2-4, 7, 8, 10-13, 15-19, 21, 23, 24, 26, 28 and 30 exhibited good to excellent antileishmanial activities with IC50 values ranging from 0.44 ± 0.02 to 32.38 ± 0.66 µg/mL. Of these, 5, 7, 19 and 28 proved to be the most active antileishmanial agents, displaying activities with IC50 values 1.78 ± 0.35, 0.44 ± 0.02, 1.91 ± 0.04 and 4.28 ± 0.75 µg/mL, respectively, which were even better than the standard drug, pentamidine (IC50 = 5.09 ± 0.04 µg/mL). This study presents the first example of exhibition of leishmanicidal potential by isatin-thiosemicarbazones and as such furnishes a solid basis for further research on these compounds to develop more potent antileishmanial agents.
• 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.
• Synthesis and biological evaluation of some N4-substituted 5-nitroisatin-3-thiosemicarbazones
  作者：Humayun Pervez、Nazia Manzoor、Muhammad Yaqub、Faiz-ul-Hassan Nasim、Khalid M. Khan

  DOI：10.1007/s00044-011-9745-7

  日期：2012.9

  A series of 5-nitroisatin-3-thiosemicarbazones 2a-2l was synthesised and evaluated for selected biological activities. The brine shrimp lethality bioassay was carried out to study their in vitro cytotoxicity potential and besides, their antifungal, phytotoxic and urease inhibitory effects were also investigated. Only compound 2j proved to be active in the brine shrimp assay exhibiting LD50 value 1.16 x 10(-3) M. Compounds 2a and 2d displayed moderate antifungal activity (50 and 40%, respectively) against M. canis. Similarly, compound 2l exhibited moderate activity (40%) against the fungal strain, A. flavus. In phytotoxicity assay, all the synthesised compounds including the reference point 2m showed weak to moderate (20-60%) activity at the highest tested concentrations (1,000 mu g and 500 mu g/ml, respectively). In urease inhibition assay, compounds 2a, 2i and 2k proved to be potent inhibitors demonstrating pronounced inhibition with IC50 values 0.440, 0.901 and 27.880 mu M, respectively. These compounds may act as leads for further studies.