5,8-dioxo-6-((2-(piperazin-1-yl)phenyl)amino)-5,8-dihydronaphthalene-1-sulfonamide | 1556861-34-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 5,8-dioxo-6-((2-(piperazin-1-yl)phenyl)amino)-5,8-dihydronaphthalene-1-sulfonamide
• 英文别名: 5,8-Dioxo-6-(2-piperazin-1-ylanilino)naphthalene-1-sulfonamide；5,8-dioxo-6-(2-piperazin-1-ylanilino)naphthalene-1-sulfonamide
• CAS: 1556861-34-7
• 化学式: C₂₀H₂₀N₄O₄S
• 分子量: 412.469
• InChiKey: OESYHAALOVZISZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  130
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  Benzyl 4-[2-[(1,4-dioxo-5-sulfamoylnaphthalen-2-yl)amino]phenyl]piperazine-1-carboxylate 在 三氟乙酸 作用下， 反应 8.0h， 以92%的产率得到5,8-dioxo-6-((2-(piperazin-1-yl)phenyl)amino)-5,8-dihydronaphthalene-1-sulfonamide
  参考文献：
  名称：

  Discovery of an Orally Selective Inhibitor of Signal Transducer and Activator of Transcription 3 Using Advanced Multiple Ligand Simultaneous Docking

  摘要：

  Targeting signal transducer and activator of transcription 3 (STAT3) is a potential anticancer strategy. However, STAT3 inhibitors with good selectivity and bioavailability are rare. The aim of this study was to discover selective direct STAT3 inhibitors with good druglikeness. By the advanced multiple ligand simultaneous docking (AMLSD) method, compound 9 was designed as an orally bioavailable STAT3 inhibitor that presented superior druggability and selectivity compared with other representative STAT3 inhibitors. 9 directly and selectively inhibited the pY705 site of STAT3 with an affinity (K-i) of 440 nM. The IC50 of 9 for MDA-MB-231 breast cancer cells was 184-fold lower than its IC50 for MCF-10A normal breast epithelial cells. 9 in vivo induced significant antitumor responses (better than gefitinib), and its therapeutic index should be over 100, indicating good safety of 9.

  DOI：

  10.1021/acs.jmedchem.6b01489

文献信息

• STAT3 INHIBITORS AND THEIR ANTICANCER USE
  申请人：Ohio State Innovation Foundation

  公开号：US20150232434A1

  公开（公告）日：2015-08-20

  In one aspect, the invention relates to substituted 6-amino-5,8-dioxo-5,8-dihydronaphthalene-1-sulfonamide analogs and derivatives thereof, substituted 4-amino-5H-naphtho[1,8-cd]isothiazol-5-one 1,1-dioxide analogs and derivatives thereof, and related compounds, which are useful as inhibitors of STAT protein activity; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating disorders of uncontrolled cellular proliferation associated with a STAT protein activity dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  本发明涉及替代的6-氨基-5,8-二氧代-5,8-二氢萘酚-1-磺酰胺类似物及其衍生物，替代的4-氨基-5H-萘并[1,8-cd]异噻唑-5-酮1,1-二氧化物类似物及其衍生物以及相关化合物，它们可用作STAT蛋白活性的抑制剂；制备这些化合物的合成方法；包含这些化合物的制药组合物；以及使用这些化合物和组合物治疗与STAT蛋白活性功能障碍相关的细胞不受控制增殖紊乱的方法。本摘要旨在作为特定领域搜索的工具，不限制本发明。
• US9783513B2
  申请人：——

  公开号：US9783513B2

  公开（公告）日：2017-10-10