(E)-N′-(1-(2,5-dichlorophenyl)ethylidene)-3-(morpholinosulfonyl)benzohydrazide | 1423715-13-2

• 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: (E)-N′-(1-(2,5-dichlorophenyl)ethylidene)-3-(morpholinosulfonyl)benzohydrazide
• 英文别名: (E)-N'-(1-(2,5-dichlorophenyl)ethylidene)-3-(morpholinosulfonyl)benzohydrazide；N-[(E)-1-(2,5-dichlorophenyl)ethylideneamino]-3-morpholin-4-ylsulfonylbenzamide
• CAS: 1423715-13-2
• 化学式: C₁₉H₁₉Cl₂N₃O₄S
• 分子量: 456.35
• InChiKey: AUBKZBOZKIREHF-LPYMAVHISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  96.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-(吗啉-4-基磺酰基)苯甲酸 在 硫酸 、 溶剂黄146 、 肼 作用下， 以 甲醇 为溶剂， 反应 12.5h， 生成 (E)-N′-(1-(2,5-dichlorophenyl)ethylidene)-3-(morpholinosulfonyl)benzohydrazide
  参考文献：
  名称：

  [EN] SUBSTITUTED (E)-N'-(1-PHENYLETHYLIDENE) BENZOHYDRAZIDE ANALOGS AS HISTONE DEMETHYLASE INHIITORS
  [FR] ANALOGUES DE (E)-N'-(1-PHÉNYLÉTHYLIDÈNE)BENZOHYDRAZIDE SUBSTITUÉS EN TANT QU'INHIBITEURS DE L'HISTONE DÉMÉTHYLASE

  摘要：

  在一个方面，该发明涉及替代(E)-N'-(1-苯乙烯基)苯甲酰肼类似物，其衍生物以及相关化合物，这些化合物可用作赖氨酸特异性组蛋白去甲基化酶的抑制剂，包括LSD1；制备这些化合物的合成方法；包含这些化合物的药物组合物；以及使用这些化合物和组合物治疗与LSD1功能障碍相关的疾病的方法。本摘要旨在作为在特定领域进行搜索的扫描工具，并不旨在限制本发明。

  公开号：

  WO2013025805A1

文献信息

• SUBSTITUTED (E)-N'-(1-PHENYLETHYLIDENE)BENZOHYDRAZIDE ANALOGS AS HISTONE DEMETHYLASE INHIBITORS
  申请人：Vankayalapati Hariprasad

  公开号：US20140163017A1

  公开（公告）日：2014-06-12

  In one aspect, the invention relates to substituted (E)-N′-(1-phenylethylidene)benzohydrazide analogs, derivatives thereof, and related compounds, which are useful as inhibitors of lysine-specific histone demethylase, including LSD1; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of using the compounds and compositions to treat disorders associated with dysfunction of the LSD1. 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.

  在一个方面，本发明涉及取代的(E)-N′-(1-苯乙烯基)苯肼类似物、其衍生物和相关化合物，它们可用作赖氨酸特异性组蛋白去甲基化酶，包括LSD1的抑制剂；制备这些化合物的合成方法；含有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LSD1功能障碍相关的疾病的方法。本摘要旨在作为搜索特定技术领域的扫描工具，不旨在限制本发明。
• Substituted (E)-N′-(1-phenylethylidene)benzohydrazide analogs as histone demethylase inhibitors
  申请人：Vankayalapati Hariprasad

  公开号：US08987335B2

  公开（公告）日：2015-03-24

  In one aspect, the invention relates to substituted (E)-N′-(1-phenylethylidene)benzohydrazide analogs, derivatives thereof, and related compounds, which are useful as inhibitors of lysine-specific histone demethylase, including LSD1; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of using the compounds and compositions to treat disorders associated with dysfunction of the LSD1. 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.

  在某个方面，本发明涉及替代的(E)-N′-(1-苯乙烯基)苯甲酰肼类似物、其衍生物和相关化合物，它们可用作赖氨酸特异性组蛋白去甲基化酶（包括LSD1）的抑制剂；制备该化合物的合成方法；包含该化合物的药物组合物；以及使用该化合物和组合物治疗与LSD1功能失调相关的疾病的方法。本摘要旨在作为搜索特定领域的扫描工具，并不意味着限制本发明。
• High-Throughput Virtual Screening Identifies Novel <i>N</i>′-(1-Phenylethylidene)-benzohydrazides as Potent, Specific, and Reversible LSD1 Inhibitors
  作者：Venkataswamy Sorna、Emily R. Theisen、Bret Stephens、Steven L. Warner、David J. Bearss、Hariprasad Vankayalapati、Sunil Sharma

  DOI：10.1021/jm400870h

  日期：2013.12.12

  Lysine specific demethylase 1 (LSD1) plays an important role in regulating histone lysine methylation at residues K4 and K9 on histone H3 and is an attractive therapeutic target in multiple malignancies. Here we report a structure-based virtual screen of a compound library containing similar to 2 million small molecular entities. Computational docking and scoring followed by biochemical screening led to the identification of a novel N'-(1-phenylethylidene)-benzohydrazide series of LSD1 inhibitors with hits showing biochemical IC(50)s in the 200-400 nM range. Hit-to-lead optimization and structure activity relationship studies aided in the discovery of compound 12, with a K-i of 31 nM. Compound 12 is reversible and specific for LSD1 as compared to the monoamine oxidases shows minimal inhibition of CYPs and hERG and inhibits proliferation and survival in several cancer cell lines, including breast and colorectal cancer. Compound 12 may be used to probe LSD1's biological role in these cancers.
• SUBSTITUTED (E)-N'-(1-PHENYLETHYLIDENE) BENZOHYDRAZIDE ANALOGS AS HISTONE DEMETHYLASE INHIITORS
  申请人：University of Utah Research Foundation

  公开号：EP2744330B1

  公开（公告）日：2020-07-15
• SUBSTITUTED (3-(5-CHLORO-2-HYDROXYPHENYL)-1-BENZOYL-1H-PYRAZOLE COMPOUNDS AS HISTONE DEMETHYLASE INHIBITORS
  申请人：University of Utah Research Foundation

  公开号：EP3010915B1

  公开（公告）日：2019-05-08