(1S,8S,10R,13R)-10-(dimethoxymethyl)-6-iodo-2-oxa-9-azatetracyclo[6.5.1.01,5.09,13]tetradeca-4,6-dien-3-one | 1375017-58-5

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: (1S,8S,10R,13R)-10-(dimethoxymethyl)-6-iodo-2-oxa-9-azatetracyclo[6.5.1.01,5.09,13]tetradeca-4,6-dien-3-one
• CAS: 1375017-58-5
• 化学式: C₁₅H₁₈INO₄
• 分子量: 403.217
• InChiKey: WPGYDGPNYQFQGE-NBZZCRHSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  48
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  甲醇 、 一叶秋碱 在 N-碘代丁二酰亚胺 作用下， 以39.8%的产率得到14-iodosecurinine
  参考文献：
  名称：

  姜黄素的意外环收缩和氧化重排反应

  摘要：

  研究了箭毒碱的溴化和氧化反应。在甲醇中水苏氨酸与三溴-异氰尿酸或1,3-二溴-5,5-二甲基乙内酰脲反应期间，观察到一个有趣且令人惊讶的重排，产生立体选择性环收缩的正苏尿碱衍生物。同时还报道了两种氧化重排产物。从这些重排进行了一些关于水仙碱反应性的初步讨论。据信它是由分子的碱性氮原子诱导的。

  DOI：

  10.1016/j.tet.2012.03.084

文献信息

• Synthesis and Antiproliferative and Metabolic Evaluations of Novel Securinine Derivatives
  作者：Marc Perez、Tahar Ayad、Philippe Maillos、Valérie Poughon、Jacques Fahy、Virginie Ratovelomanana-Vidal

  DOI：10.1021/acsmedchemlett.5b00441

  日期：2016.4.14

  New securinine analogues have been prepared by semisynthesis. Two series were developed using either Suzuki or Sonogashira cross coupling reactions. The in vitro cytotoxicity of the compounds was assayed against HCT-116 colon cancer cells. The most potent derivatives showed promising growth inhibition on four tumoral cell lines giving a valuable insight on the structure–activity relationship (SAR)

  通过半合成已经制备了新的箭毒碱类似物。使用Suzuki或Sonogashira交叉偶联反应开发了两个系列。在体外的化合物的细胞毒性进行测定针对HCT-116结肠癌细胞。最有效的衍生物在四种肿瘤细胞系上显示出有希望的生长抑制作用，从而提供了关于水cur碱结构-活性关系（SAR）的宝贵见解。此外，在IC 50高达60 nM的情况下，观察到了对A-375（黑色素瘤）的高抗增殖作用。
• [EN] SMALL MOLECULE SECURININE AND NORSECURININE ANALOGS AND THEIR USE IN INHIBITING MYELOPEROXIDASE<br/>[FR] ANALOGUES DE SÉCURININE ET DE NORSÉCURININE À PETITES MOLÉCULES ET LEUR UTILISATION POUR INHIBER LA MYÉLOPEROXYDASE
  申请人：MIRX PHARMACEUTICALS LLC

  公开号：WO2015051276A1

  公开（公告）日：2015-04-09

  The present invention relates to novel securinine and norsecurine analogs that have reduced or non-reduced gamma-delta bond. The present invention also provides for methods of using securinine analogs, comprising administering one or more of the analogs to a myeloperoxidase enzyme, such as an enzyme with or proximal to a cell. As set out herein, the securinine analogs directly bind to and inhibit myeloperoxidase (MPO) activity. Accordingly, contacting or administering the analogs to an MPO enzyme allows for inhibition of MPO activity.

  本发明涉及一种具有减少或未减少γ-δ键的新型安全琳和诺安全琳类似物。本发明还提供了使用安全琳类似物的方法，包括将一个或多个类似物给予髓过氧化物酶酶，例如与细胞接近或接近的酶。如本文所述，安全琳类似物直接结合并抑制髓过氧化物酶（MPO）活性。因此，将类似物与MPO酶接触或给予类似物可使MPO活性受到抑制。
• Securinine and norsecurinine analogue compounds for the treatment of myeloid disorders
  申请人：CASE WESTERN RESERVE UNIVERSITY

  公开号：US10806723B2

  公开（公告）日：2020-10-20

  The present application relates to securinine or norsecurinine analogues that, when administered to immature myeloid cells, promote differentiation of these cells to mature cells that do not readily proliferate. Therefore, the agents are useful in the treatment of myeloid disorders including myeloproliferative disorders, acute myeloid leukemia, and autoimmune diseases. The agents may also be used as a myeloablative agent in conjunction with a bone marrow transplant or stem cell therapy.

  本申请涉及securinine或norsecurinine类似物，当对未成熟髓系细胞施用时，可促进这些细胞分化为不易增殖的成熟细胞。因此，这些制剂可用于治疗髓系疾病，包括骨髓增生性疾病、急性髓系白血病和自身免疫性疾病。这些制剂还可用作骨髓移植或干细胞疗法的髓鞘脱落剂。
• SMALL MOLECULE SECURININE AND NORSECURININE ANALOGS AND THEIR USE IN CANCERS, INFLAMMATORY DISEASES AND INFECTIONS
  申请人：GUNDLURU Mahesha K.

  公开号：US20160229861A1

  公开（公告）日：2016-08-11

  The present invention relates to novel securinine and norsecurine analogs and their applicapility in treating cellular proliferative disorders.
• SMALL MOLECULE SECURININE AND NORSECURININE ANALOGS AND THEIR USE IN INHIBITING MYELOPEROXIDASE
  申请人：GUNDLURU Mahesh K.

  公开号：US20160250196A1

  公开（公告）日：2016-09-01

  The present invention relates to novel securinine and norsecurine analogs that have reduced or non-reduced gamma-delta bond. The present invention also provides for methods of using securinine analogs, comprising administering one or more of the analogs to a myeloperoxidase enzyme, such as an enzyme with or proximal to a cell. As set out herein, the securinine analogs directly bind to and inhibit myeloperoxidase (MPO) activity. Accordingly, contacting or administering the analogs to an MPO enzyme allows for inhibition of MPO activity.