methyl 3-(N,N-dimethylsulfamoyl)benzoate | 823833-29-0

• 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: methyl 3-(N,N-dimethylsulfamoyl)benzoate
• 英文别名: Methyl 3-(dimethylsulfamoyl)benzoate
• CAS: 823833-29-0
• 化学式: C₁₀H₁₃NO₄S
• mdl: MFCD06622609
• 分子量: 243.284
• InChiKey: TZKDPBATMOYEBO-UHFFFAOYSA-N

物化性质

• 沸点：
  371.3±44.0 °C(Predicted)
• 密度：
  1.261±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  72.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 3-(N,N-dimethylsulfamoyl)benzoate 在 锂硼氢 作用下， 以 乙醇 为溶剂， 以70%的产率得到3-(hydroxymethyl)-N,N-dimethylbenzenesulfonamide
  参考文献：
  名称：

  [EN] INDOLE AND AZAINDOLE HALOALLYLAMINE DERIVATIVE INHIBITORS OF LYSYL OXIDASES AND USES THEREOF
  [FR] DÉRIVÉ D'HALOALLYLAMINES INDOLE ET AZAINDOLE COMME INHIBITEURS DE LYSYL OXYDASES, ET LEURS UTILISATIONS

  摘要：

  公开号：

  WO2017136871A9
• 作为产物：
  描述：

  3-氯磺酰基苯甲酸 在 硫酸 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 12.0h， 生成 methyl 3-(N,N-dimethylsulfamoyl)benzoate
  参考文献：
  名称：

  Synthesis and biological evaluation of novel (E)-N′-(2,3-dihydro-1H-inden-1-ylidene) benzohydrazides as potent LSD1 inhibitors

  摘要：

  Lysine specific demethylase 1 (LSD1) plays an important role in regulating histone lysine methylation at residues K4 and K9 on histone H3 and is recognized as an attractive therapeutic target in multiple malignancies. In this study, a series of novel (E)-N'-(2,3-dihydro-1H-inden-1-ylidene) benzohydrazides were synthesized and biologically evaluated for their potential LSD1 inhibitory effect. Among them, compounds 5a and 5n showed the most potent LSD1 inhibitory activity with IC50 values of 1.4 and 1.7 nM, respectively, which were about 10 times more potent compared with (E)-N-(1-(5-chloro-2-hydroxyphenyl) ethylidene)-3-(morpholinosulf-only) benzohydrazide (J. Med. Chem. 2013, 56, 9496-9508; as reference compound). Compounds 5a and 5n also exhibited marked anti-proliferation activities against cancer cell lines that highly expressed LSD1. These results suggest that these optimized compounds might be served as promising LSD1 inhibitors against cancer, which merit further study. (C) 2016 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2015.06.054

文献信息

• [EN] SUBSTITUTED (E)-N'-(1-PHENYLETHYLIDENE) BENZOHYDRAZIDE ANALOGS AS HISTONE DEMETHYLASE INHIITORS<br/>[FR] ANALOGUES DE (E)-N'-(1-PHÉNYLÉTHYLIDÈNE)BENZOHYDRAZIDE SUBSTITUÉS EN TANT QU'INHIBITEURS DE L'HISTONE DÉMÉTHYLASE
  申请人：UNIV UTAH RES FOUND

  公开号：WO2013025805A1

  公开（公告）日：2013-02-21

  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，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。
• 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。
• Indole and azaindole haloallylamine derivative inhibitors of lysyl oxidases and uses thereof
  申请人：PHARMAXIS LTD.

  公开号：US10717734B2

  公开（公告）日：2020-07-21

  The present invention relates to novel compounds which are capable of inhibiting certain amine oxidase enzymes. These compounds are useful for treatment of a variety of indications, e.g., fibrosis, cancer and/or angiogenesis in human subjects as well as in pets and livestock. In addition, the present invention relates to pharmaceutical compositions containing these compounds, as well as various uses thereof.

  本发明涉及能够抑制某些胺氧化酶的新型化合物。这些化合物可用于治疗各种适应症，如人类、宠物和家畜的纤维化、癌症和/或血管生成。此外，本发明还涉及含有这些化合物的药物组合物及其各种用途。
• 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.