N,N'-hexanediyl-bis-methanesulfonamide | 13910-94-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磺酸及其衍生物
• 英文名称: N,N'-hexanediyl-bis-methanesulfonamide
• 英文别名: N,N'-Hexandiyl-bis-methansulfonamid；N-{6-[(methylsulfonyl)amino]hexyl}methanesulfonamide；N-[6-(methanesulfonamido)hexyl]methanesulfonamide
• CAS: 13910-94-6
• 化学式: C₈H₂₀N₂O₄S₂
• mdl: MFCD02371271
• 分子量: 272.39
• InChiKey: GBIKLLVSHBWFKJ-UHFFFAOYSA-N

物化性质

• 熔点：
  128-129 °C(Solv: water (7732-18-5))
• 沸点：
  427.6±55.0 °C(Predicted)
• 密度：
  1.236±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  16
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(4-fluorobenzyl)-8-hydroxy-5-bromo-1,6-naphthyridine-7-carboxamide 、 N,N'-hexanediyl-bis-methanesulfonamide 在 吡啶 、 copper(I) oxide 作用下， 反应 10.0h， 以35%的产率得到N-[(4-fluorophenyl)methyl]-8-hydroxy-5-[6-(methanesulfonamido)hexyl-methylsulfonylamino]-1,6-naphthyridine-7-carboxamide
  参考文献：
  名称：

  Repositioning HIV-1 Integrase Inhibitors for Cancer Therapeutics: 1,6-Naphthyridine-7-carboxamide as a Promising Scaffold with Drug-like Properties

  摘要：

  Among a large number of HIV-1 integrase (IN) inhibitors, the 8-hydroxy-[1,6]naphthyridines (i.e., L-870,810) were one of the promising class of antiretroviral drugs developed by Merck Laboratories. In spite of its remarkable potency and efficacy, unfortunately upon completion of phase I clinical studies, development of L-870,810 was halted. Because of its desirable pharmacological and pharmaceutical properties we were intrigued to design novel analogues of L-870,810 with goals to (1) improve upon limitations of naphthyridine-7-carboxamides as antiviral agents and (2) to reposition their use as innovative cytotoxic agents for cancer therapeutics. Herein, we report on the design and synthesis of a series of 1,6-naphthyridine-7-carboxamides with various substitutions at the 5- and 8-positions. All the new 5-substituted-8-hydroxy-[1,6]naphthyridines were potent IN inhibitors and the 5-substituted-8-amino-[1,6]naphthyridines were significantly cytotoxic. Further optimization of the 5,8-disubstituted-[1,6]naphthyridines with structural variation on 7-carboxamide delivered novel compounds with significant cytotoxicity in a panel of cancer cell lines and effective inhibition against select oncogenic kinases.

  DOI：

  10.1021/jm300667v
• 作为产物：
  描述：

  1,6-己二胺 、 甲基磺酰氯 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N,N'-hexanediyl-bis-methanesulfonamide
  参考文献：
  名称：

  [EN] COMPOSITIONS AND METHODS FOR MODULATING HEXIM1 EXPRESSION
  [FR] COMPOSITIONS ET PROCÉDÉS DE MODULATION DE L'EXPRESSION D'HEXIM1

  摘要：

  一系列诱导己六亚甲基双乙酰胺（HMBA）衍生物（化学式I）的效力，能够诱导己六亚甲基双乙酰胺诱导蛋白1（HEXIM1）在癌细胞中的表达已经确定。揭示了在癌细胞和HIV细胞中诱导HEXIM1表达和细胞分化的方法。还讨论了对称和非对称的HMBA类似物的优化。

  公开号：

  WO2015116968A1

文献信息

• NOVEL COMPOUND HAVING MULTIMER STRUCTURE OF XANTHENE DERIVATIVE, COLORING COMPOSITION, INK FOR INKJET RECORDING, METHOD OF INKJET RECORDING, COLOR FILTER, AND COLOR TONER
  申请人：FUJIFILM CORPORATION

  公开号：US20140176653A1

  公开（公告）日：2014-06-26

  There is provided a compound represented by formula (1): in formula (1), L represents a divalent to tetravalent linking group; D represents a residue obtained by removing 1 to 5 hydrogen atoms from a compound represented by formula (2); m represents an integer of 1 to 10, however, each L may be the same with or different from every other L; n represents an integer of 2 to 10, however, each D may be the same with or different from every other D; and in formula (2), each of R 4 to R 24 independently represents a hydrogen atom or a substituent, provided that formula (2) has at least one or more ionic hydrophilic groups.

  提供了一种由公式(1)表示的化合物：在公式(1)中，L代表二价到四价的连接基团；D代表通过从由公式(2)表示的化合物中去除1到5个氢原子获得的残基；m代表1到10的整数，但是，每个L可以相同也可以不同于其他L；n代表2到10的整数，但是，每个D可以相同也可以不同于其他D；在公式(2)中，R4到R24中的每一个独立地代表一个氢原子或一个取代基，前提是公式(2)至少有一个或更多的离子亲水基团。
• [EN] COMPOSITIONS AND METHODS FOR MODULATING HEXIM1 EXPRESSION<br/>[FR] COMPOSITIONS ET PROCÉDÉS DE MODULATION DE L'EXPRESSION D'HEXIM1
  申请人：UNIV CASE WESTERN RESERVE

  公开号：WO2015116968A1

  公开（公告）日：2015-08-06

  The potency of a series of Hexamethylene bis-acetamide (HMBA) derivatives of formula I, that induce Hexamethylene bis-acetamide inducible protein 1 (HEXIM1 ) was determined in cancer cells. The method of inducing HEXIM1 expression and cell differentiation in cancer and HIV cells are disclosed. Optimization of HMBA analogs that are symmetrical and unsymmetrical are also discussed.

  一系列诱导己六亚甲基双乙酰胺（HMBA）衍生物（化学式I）的效力，能够诱导己六亚甲基双乙酰胺诱导蛋白1（HEXIM1）在癌细胞中的表达已经确定。揭示了在癌细胞和HIV细胞中诱导HEXIM1表达和细胞分化的方法。还讨论了对称和非对称的HMBA类似物的优化。
• New Epoxide Resins by Reaction of Epichlorohydrin with Sulfonamides
  作者：Merrill Cohen

  DOI：10.1021/ie50550a024

  日期：1955.10
• Repositioning HIV-1 Integrase Inhibitors for Cancer Therapeutics: 1,6-Naphthyridine-7-carboxamide as a Promising Scaffold with Drug-like Properties
  作者：Li-Fan Zeng、Yong Wang、Roza Kazemi、Shili Xu、Zhong-Liang Xu、Tino W. Sanchez、Liu-Meng Yang、Bikash Debnath、Srinivas Odde、Hua Xie、Yong-Tang Zheng、Jian Ding、Nouri Neamati、Ya-Qiu Long

  DOI：10.1021/jm300667v

  日期：2012.11.26

  Among a large number of HIV-1 integrase (IN) inhibitors, the 8-hydroxy-[1,6]naphthyridines (i.e., L-870,810) were one of the promising class of antiretroviral drugs developed by Merck Laboratories. In spite of its remarkable potency and efficacy, unfortunately upon completion of phase I clinical studies, development of L-870,810 was halted. Because of its desirable pharmacological and pharmaceutical properties we were intrigued to design novel analogues of L-870,810 with goals to (1) improve upon limitations of naphthyridine-7-carboxamides as antiviral agents and (2) to reposition their use as innovative cytotoxic agents for cancer therapeutics. Herein, we report on the design and synthesis of a series of 1,6-naphthyridine-7-carboxamides with various substitutions at the 5- and 8-positions. All the new 5-substituted-8-hydroxy-[1,6]naphthyridines were potent IN inhibitors and the 5-substituted-8-amino-[1,6]naphthyridines were significantly cytotoxic. Further optimization of the 5,8-disubstituted-[1,6]naphthyridines with structural variation on 7-carboxamide delivered novel compounds with significant cytotoxicity in a panel of cancer cell lines and effective inhibition against select oncogenic kinases.
• Lead optimization of HMBA to develop potent HEXIM1 inducers
  作者：Bo Zhong、Rati Lama、Wannarasmi Ketchart、Monica M. Montano、Bin Su

  DOI：10.1016/j.bmcl.2014.01.025

  日期：2014.3

  The potency of a series of Hexamethylene bis-acetamide (HMBA) derivatives inducing Hexamethylene bis-acetamide inducible protein 1 (HEXIM1) was determined in LNCaP prostate cancer cells. Several compounds with unsymmetrical structures showed significantly improved activity. Distinct from HMBA, these analogs have increased hydrophobicity and can improve the short half-life of HMBA, which is one of the factors that have limited the application of HMBA in clinics. The unsymmetrical scaffolds of the new analogs provide the basis for further lead optimization of the compounds using combinatorial chemistry strategy. Published by Elsevier Ltd.