(10-{3-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-propyl}-10H-phenothiazin-2-ylmethylene)-malononitrile | 58271-71-9

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: (10-{3-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-propyl}-10H-phenothiazin-2-ylmethylene)-malononitrile
• 英文别名: 2-[[10-[3-[4-(2-Hydroxyethyl)piperazin-1-yl]propyl]phenothiazin-2-yl]methylidene]propanedinitrile
• CAS: 58271-71-9
• 化学式: C₂₅H₂₇N₅OS
• 分子量: 445.588
• InChiKey: KZDSOTGJTCVKOP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  10-{3-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-propyl}-10H-phenothiazine-2-carbonitrile 在 镍 哌啶 作用下， 以 甲酸 、 乙醇 、 水 为溶剂， 生成 (10-{3-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-propyl}-10H-phenothiazin-2-ylmethylene)-malononitrile
  参考文献：
  名称：

  氟苯嗪的新的2-取代的类似物的合成和生物活性。

  摘要：

  DOI：

  10.1021/jm00225a005

文献信息

• Methods of Treating Disorders Associated with Protein Aggregation
  申请人：Pak Stephen C.

  公开号：US20130024953A1

  公开（公告）日：2013-01-24

  The present invention relates to methods of treatment of clinical disorders associated with protein aggregation comprising administering, to a subject, an effective amount of an anti-protein aggregate (“APA”) compound selected from the group consisting of pimozide, fluphenazine (e.g., fluphenazine hydrochloride), tamoxifen (e.g., tamoxifen citrate), taxol, cantharidin, cantharidic acid, salts thereof and their structurally related compounds. It is based, at least in part, on the discovery that each of the aforelisted compounds were able to promote degradation of aggregated ATZ protein in a Caenorhabditis elegans model system. According to the invention, treatment with one or more of these APA compounds may be used to ameliorate the symptoms and signs of AT deficiency as well as other disorders marked by protein aggregation, including, but not limited to, Alzheimer's Disease, Parkinson's Disease, and Huntington's Disease.

  本发明涉及与蛋白质聚集相关的临床疾病的治疗方法，包括向受试者施用来自以下组中选择的抗蛋白质聚集（“APA”）化合物的有效量：哌唑酮，氟哌利多（例如氟哌利多盐酸盐），他莫昔芬（例如他莫昔芬柠檬酸盐），紫杉醇，蝉蜕素，蝉酸及其盐和结构相关化合物。本发明至少部分基于以下发现：上述每种化合物均能促进Caenorhabditis elegans模型系统中聚集的ATZ蛋白的降解。根据本发明，使用这些APA化合物之一或多个进行治疗，可用于缓解AT缺陷以及其他由蛋白质聚集标记的疾病的症状和体征，包括但不限于阿尔茨海默病、帕金森病和亨廷顿病。
• METHODS OF TREATING DISORDERS ASSOCIATED WITH PROTEIN AGGREGATION
  申请人：University Of Pittsburgh - of the Commonwealth System of Higher Education

  公开号：US20150265626A1

  公开（公告）日：2015-09-24

  The present invention relates to methods of treatment of clinical disorders associated with protein aggregation comprising administering, to a subject, an effective amount of an anti-protein aggregate (“APA”) compound selected from the group consisting of pimozide, fluphenazine (e.g., fluphenazine hydrochloride), tamoxifen (e.g., tamoxifen citrate), taxol, cantharidin, cantharidic acid, salts thereof and their structurally related compounds. It is based, at least in part, on the discovery that each of the aforelisted compounds were able to promote degradation of aggregated ATZ protein in a Caenorhabditis elegans model system. According to the invention, treatment with one or more of these APA compounds may be used to ameliorate the symptoms and signs of AT deficiency as well as other disorders marked by protein aggregation, including, but not limited to, Alzheimer's Disease, Parkinson's Disease, and Huntington's Disease.

  本发明涉及治疗与蛋白质聚集相关的临床疾病的方法，包括向受试者施用来自以下组中选择的抗蛋白质聚集（“APA”）化合物的有效量：哌唑酮，氟苯奈嗪（例如，氟苯奈嗪盐酸盐），他莫昔芬（例如，他莫昔芬柠檬酸盐），紫杉醇，鲍鱼毒素，鲍鱼毒酸，其盐及其结构相关化合物。该发明至少部分基于以下发现：上述每种化合物均能够促进在秀丽隐杆线虫模型系统中聚集的ATZ蛋白质的降解。根据本发明，使用这些APA化合物中的一个或多个进行治疗可以用于改善AT缺乏症状和体征以及其他以蛋白质聚集为特征的疾病，包括但不限于阿尔茨海默病、帕金森病和亨廷顿病。
• BOSSLE P. C.; FERGUSON C. P.; SULTAN W. E.; LENNOX W. J.; DUDLEY G. E.; R+, J. MED. CHEM. <JMCM-AR>, 1976, 19, NO 3, 370-373
  作者：BOSSLE P. C.、 FERGUSON C. P.、 SULTAN W. E.、 LENNOX W. J.、 DUDLEY G. E.、 R+

  DOI：——

  日期：——
• US9072772B2
  申请人：——

  公开号：US9072772B2

  公开（公告）日：2015-07-07
• US9452171B2
  申请人：——

  公开号：US9452171B2

  公开（公告）日：2016-09-27