9-(2-Methylbutyl)-3-methylene-1,5-bis(p-tolylsulfonyl)-1,5,9-triazacyclododecane

• 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-(2-Methylbutyl)-3-methylene-1,5-bis(p-tolylsulfonyl)-1,5,9-triazacyclododecane
• 英文别名: 9-(2-methylbutyl)-3-methylidene-1,5-bis-(4-methylphenyl)sulfonyl-1,5,9-triazacyclododecane
• 化学式: C₂₉H₄₃N₃O₄S₂
• 分子量: 561.81
• InChiKey: SNSWWRDSINTZSL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  38
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  94.8
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  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 25.5h， 生成 9-(2-Methylbutyl)-3-methylene-1,5-bis(p-tolylsulfonyl)-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

文献信息

• 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。