desmethyl desamino pateamine A

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯类和类似物
• 英文名称: desmethyl desamino pateamine A
• 英文别名: (3S,6Z,8E,11S)-3-[(1E,3E,5E)-7-(dimethylamino)-2,5-dimethylhepta-1,3,5-trienyl]-9,11-dimethyl-4,12-dioxa-20-thia-21-azabicyclo[16.2.1]henicosa-1(21),6,8,18-tetraene-5,13-dione
• 化学式: C₃₀H₄₂N₂O₄S
• 分子量: 526.74
• InChiKey: VSVORQIMRUVRPE-MMPYLIGOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  37
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  97
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (2E,4E)-N,N,3-trimethyl-5-(tributylstannyl)penta-2,4-dien-1-amine 、 (6Z,8E)-(3S,11S)-3-((E)-2-Bromo-propenyl)-9,11-dimethyl-4,12-dioxa-20-thia-21-aza-bicyclo[16.2.1]henicosa-1(21),6,8,18-tetraene-5,13-dione 在 tris(dibenzylideneacetone)dipalladium(0) chloroform complex 、 三苯胂 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以76%的产率得到desmethyl desamino pateamine A
  参考文献：
  名称：

  免疫抑制和抗肿瘤天然产物 Pateamine A 中单独结合和支架结构域的证据：设计、合成和活性研究导致有效的简化衍生物

  摘要：

  Pateamine A (PatA) 是一种来自 Mycale sp. 的海洋代谢物，是 T 细胞受体发出的细胞内信号转导途径的有效抑制剂，可导致细胞因子如白细胞介素 2 (IL-2) 的转录。基于 PatA 的结构和最初的生物学结果，提出了一个假设，即 PatA 结构中存在不同的结合和支架结构域，与它推定的细胞受体的相互作用有关。我们采用涉及 Hantzsch 耦合策略的高度收敛方法，通过制备简化的 PatA 衍生物（去甲基、去氨基 PatA、DMDAPatA、3）来探讨这一假设。与 PatA 相比，该衍生物的合成步骤少了 10 步，并且确实发现其具有更高的效力（IC50 0.81 +/- 0 27 nM) 相对于 PatA (IC50 4.01 +/- 0.94 nM) 抑制 IL-2 产生，从而为结合/支架结构域假设提供支持。此外，为了找到更稳定的衍生物并进一步了解构效关系，在 IL-2

  DOI：

  10.1021/ja040065s

文献信息

• Alpha-amino pateamine A derivatives and methods for treating chronic lymphocytic leukemia
  申请人：The Texas A&M University System

  公开号：US10407444B2

  公开（公告）日：2019-09-10

  Pateamine A derivatives and pharmaceutical compositions that include the derivatives. The pateamine A derivatives are α-amino pateamine A derivatives that lack the C5-methyl group of pateamine A.

  儿茶酚胺 A 衍生物和包括这些衍生物的药物组合物。儿茶酚胺 A 衍生物是缺少儿茶酚胺 A 的 C5-甲基的 α-氨基儿茶酚胺 A 衍生物。
• Beta-amino pateamine a derivatives and methods for treating chronic lymphocytic leukemia
  申请人：The Texas A&M University System

  公开号：US10889596B2

  公开（公告）日：2021-01-12

  Pateamine A derivatives, pharmaceutical compositions that include the derivatives, and methods for treating chronic lymphocytic leukemia using the derivatives.

  儿茶酚胺 A 衍生物、包括这些衍生物的药物组合物，以及使用这些衍生物治疗慢性淋巴细胞白血病的方法。
• Potent immunosuppressive agents derivatives and use
  申请人：Romo Daniel

  公开号：US20070149581A1

  公开（公告）日：2007-06-28

  Provided herein include compositions, all related stereoisomers as well as pharmaceutically acceptable salts provided as simplified analogs of pateamine A, in which the analogs generally are devoid of the C3-amino and C5-methyl groups, also referred to as desmethyl, desamino-pateamine A. Suitable analogs provide anticancer and antiproliferative effects in vivo and in vitro by a novel drugs mechanism of action described herein for pateamine A, including inhibition of eIF4A-dependent translation initiation. As with pateamine A, as described herein, suitable analogs cause cell cycle arrest or induce apoptosis in transformed cells. However, toxicity of such compounds to slow growing normal cells is low. In addition, such analogs, like pateamine A, target translation initiation factors and are useful as anticancer and antiproliferative agents in subjects in need thereof. Moreover, the analogs, like pateamine A, are valuable molecular probes for evalutaion of eukaryotic translation initiation and as lead compounds for development of improved anticancer agents.
• POTENT IMMUNOSUPPRESSIVE AGENTS, DERIVATIVES AND USES
  申请人：Romo Daniel

  公开号：US20110053994A1

  公开（公告）日：2011-03-03

  Provided herein include compositions, all related stereoisomers as well as pharmaceutically acceptable salts provided as simplified analogs of pateamine A, in which the analogs generally are devoid of the C3-amino and C5-methyl groups, also referred to as desmethyl, desamino-pateamine A. Suitable analogs provide anticancer and antiproliferative effects in vivo and in vitro by a novel drugs mechanism of action described herein for pateamine A, including inhibition of eIF4A-dependent translation initiation. As with pateamine A, as described herein, suitable analogs cause cell cycle arrest or induce apoptosis in transformed cells. However, toxicity of such compounds to slow growing normal cells is low. In addition, such analogs, like pateamine A, target translation initiation factors and are useful as anticancer and antiproliferative agents in subjects in need thereof. Moreover, the analogs, like pateamine A, are valuable molecular probes for evalutaion of eukaryotic translation initiation and as lead compounds for development of improved anticancer agents.
• ALPHA-AMINO PATEAMINE A DERIVATIVES AND METHODS FOR TREATING CHRONIC LYMPHOCYTIC LEUKEMIA
  申请人：The Texas A&M University System

  公开号：US20180118764A1

  公开（公告）日：2018-05-03

  Pateamine A derivatives and pharmaceutical compositions that include the derivatives. The pateamine A derivatives are α-amino pateamine A derivatives that lack the C5-methyl group of pateamine A.