9-benzyl-3-methylene-1,5-ditosyl-1,5,9-triazacyclododecane (CADA) | 182316-44-5

• 物质功能分类: 有机原料 - 烃类化合物及其衍生物 - 芳香烃
• 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: 9-benzyl-3-methylene-1,5-ditosyl-1,5,9-triazacyclododecane (CADA)
• 英文别名: 9-benzyl-3-methylene-1,5-bis(4-methylbenzenesulfonyl)-1,5,9-triazacyclododecane；9-benzyl-3-methylene-1,5-ditosyl-1,5,9-triazacyclododecane；CADA；9-Benzyl-3-methylene-1,5-bis(p-tolylsulfonyl)-1,5,9-triazacyclododecane；9-benzyl-3-methylidene-1,5-bis-(4-methylphenyl)sulfonyl-1,5,9-triazacyclododecane
• CAS: 182316-44-5
• 化学式: C₃₁H₃₉N₃O₄S₂
• 分子量: 581.8
• InChiKey: SRJIECKMPIRMJJ-UHFFFAOYSA-N

物化性质

• 熔点：
  160-164 °C(Solv: ethyl acetate (141-78-6))
• 沸点：
  706.2±70.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  40
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  94.8
• 氢给体数：
  0
• 氢受体数：
  7

安全信息

• 储存条件：
  -20°C下保存，需避光、干燥且密封。

制备方法与用途

Cyclotriazadisulfonamide (CADA) 是一个特异性的CD4靶向的HIV进入抑制剂，它通过信号肽依赖的方式抑制CD4的内质网腔共翻译转位过程。

反应信息

• 作为反应物：
  描述：

  9-benzyl-3-methylene-1,5-ditosyl-1,5,9-triazacyclododecane (CADA) 在 1-氯乙基氯甲酸酯 、 sodium cyanoborohydride 作用下， 以 甲醇 、 1,2-二氯乙烷 为溶剂， 反应 41.5h， 生成 3-Methylene-1,5-bis(p-tolylsulfonyl)-9-(2-pyridylmethyl)-1,5,9-triazacyclododecane
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship Studies of CD4 Down-Modulating Cyclotriazadisulfonamide (CADA) Analogues

  摘要：

  HIV attachment via the CD4 receptor is an important target for developing novel approaches to HIV chemotherapy. Cyclotriazadisulfonamide (CADA) inhibits HIV at submicromolar levels by specifically down-modulating cell-surface and intracellular CD4. An effective five-step synthesis of CADA in 30% overall yield is reported. This synthesis has also been modified to produce more than 50 analogues. Many tail-group analogues have been made by removing the benzyl tail of CADA and replacing it with various alkyl, acyl, alkoxycarbonyl and aminocarbonyl substituents. A series of sidearm analogues, including two unsymmetrical compounds, have also been prepared by modifying the CADA synthesis, replacing the toluenesulfonyl sidearms with other sulfonyl groups. Testing 30 of these compounds in MT-4 cells shows a wide range of CD4 down-modulation potency, which correlates with ability to inhibit HIV-1. Three-dimensional quantitative structure-activity relationship (3D-QSAR) models were constructed using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) approaches. The X-ray crystal structures of four compounds, including CADA, show the same major conformation of the central 12-membered ring. The solid-state structure of CADA was energy minimized and used to generate the remaining 29 structures, which were similarly minimized and aligned to produce the 3D-QSAR models. Both models indicate that steric bulk of the tail group, and, to a lesser extent, the sidearms mainly determine CD4 down-modulation potency in this series of compounds.

  DOI：

  10.1021/jm0582524
• 作为产物：
  描述：

  双(2-氰基乙基)胺 在 镍 sodium hydroxide 、 氢气 、 sodium hydride 、 碳酸氢钠 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 80.0~100.0 ℃ 、275.79 kPa 条件下， 反应 71.0h， 生成 9-benzyl-3-methylene-1,5-ditosyl-1,5,9-triazacyclododecane (CADA)
  参考文献：
  名称：

  双环三胺的合成、构象和碱性

  摘要：

  描述了几种双环三胺的多步合成，所有这些都具有嵌入的 1,5,9-三氮杂环十二烷环。在 1,5,9-三氮杂双环 [7.3.3] 十五烷 12、13、15 和 16 中，两个氮被三个碳桥接。这些三胺的单质子化形式通过涉及桥和两个桥头氮的氢键网络高度稳定，在其单质子化和双质子化形式的酸度中产生超过 8 pK(a) 单位的差异。1,5,9-三氮杂双环[9.1.1]十三烷（23）和7-甲基-1,5,9-三氮杂双环[5.5.0]十二烷（39）中的一碳和零碳桥不会增强它们的单质子化形式的稳定性。12.HI 和 16.HI 的 X 射线晶体结构和计算研究揭示了与 15.HI 相似但稍弱的氢键网络。13.HI (14.4 +/- 0.2 kcal/mol)、16.HI (15.0 +/- 0.1 kcal/mol) 和 16 (8.8 +/- 0.3 kcal/mol) 构象反转的活化自由能通过以下方式测量变温

  DOI：

  10.1021/ja030236d

文献信息

• Anti-viral triaza compounds and compositions
  申请人：The Research Foundation of State University of New York

  公开号：US06342492B1

  公开（公告）日：2002-01-29

  The invention relates to a family of new synthetic triamine compounds which can be used in antiviral pharmaceutical compositions.

  本发明涉及一族新的合成三胺化合物，可用于抗病毒药物组合物中。
• [EN] TRIAZACYCLODODECANSULFONAMIDE ("TCD")-BASED PROTEIN SECRETION INHIBITORS<br/>[FR] INHIBITEURS DE SÉCRÉTION DE PROTÉINE À BASE DE TRIAZACYCLODODÉCANSULFONAMIDE ("TCD")
  申请人：KEZAR LIFE SCIENCES

  公开号：WO2019178510A1

  公开（公告）日：2019-09-19

  Provided herein are triazacyclododecansulfonamide ("TCD")-based protein secretion inhibitors, such as inhibitors of Sec61, methods for their preparation, related pharmaceutical compositions, and methods for using the same. For example, provided herein are compounds of Formula (I) and pharmaceutically acceptable salts and compositions including the same. The compounds disclosed herein may be used, for example, in the treatment of diseases including inflammation and/or cancer.

  本文提供了基于三氮杂环十二烷磺酰胺（"TCD"）的蛋白质分泌抑制剂，例如Sec61的抑制剂，其制备方法，相关的药物组合物，以及使用它们的方法。例如，本文提供了符合Formula（I）的化合物及其药用盐和包括它们的组合物。本文披露的化合物可以用于治疗炎症和/或癌症等疾病。
• Anti-viral triaza compounds
  申请人：——

  公开号：US20020019423A1

  公开（公告）日：2002-02-14

  A method of inhibiting viruses in which a virus is contacted with an antiviral amount of a compound of formula I. Activity is shown against HIV and other viruses. 1 wherein W is a bridge carbon which has a polar or non-polar side group; X and Y independently are an aromatic group, an alkyl group, a sulfonyl group or a carbonyl group, said aromatic group is selected from the group consisting of Ar, Ar sulfonyl, Ar carboxy and Ar alkyl, where Ar is an aromatic cyclic or aromatic heterocyclic ring having from five to seven members; said alkyl group having from one to ten carbons; Z is a group listed for X and Y, a fused aryl moiety having from seven to ten carbons or hydrogen; a, d and e independently are a number from zero to 10; c and b independently are a number from one to 10; and the formula is cyclic or acyclic and includes sufficient hydrogens for a stable molecule.

  一种抑制病毒的方法，其中将病毒与式I化合物的抗病毒量接触。该化合物对HIV和其他病毒表现出活性。式中，W是具有极性或非极性侧基的桥碳；X和Y独立地是芳香基，烷基，磺酰基或羰基，所述芳香基从由五到七个成员组成的芳香环或芳香杂环环中选择，所述烷基具有一到十个碳；Z是列在X和Y中的一组，具有七到十个碳的融合芳基基团或氢；a，d和e独立地是从零到10的数字；c和b独立地是从一到10的数字；该式是环状或非环状的，并包括足够的氢以形成稳定的分子。
• Triaza Compound Immunoregulatory Agents
  申请人：Bell Thomas

  公开号：US20090048222A1

  公开（公告）日：2009-02-19

  The invention provides certain macrocyclic triaza compounds which down-regulate CD4 expression for use in the treatment of autoimmune diseases and inflammatory diseases or conditions. In a specific embodiment, the invention provides certain naphthalene substituted triaza macrocycles which exhibit high activity for down regulation of CD4 expression. In particular, triaza macrocycles having dansyl groups are provided for use in pharmaceutical compositions.

  本发明提供了某些大环三氮杂化合物，其下调CD4表达用于治疗自身免疫性疾病和炎症性疾病或情况。在具体实施例中，本发明提供了某些萘取代的三氮杂大环，其表现出高活性以下调CD4表达。特别地，提供了具有丹磺酰基团的三氮杂大环，用于制备制药组合物。
• EP0809504A4
  申请人：——

  公开号：EP0809504A4

  公开（公告）日：1998-11-04