1,1'-<2,6-pyridylbis(methylene)>bis<4,8,11-tris(p-tolylsulfonyl)-1,4,8,11-tetraazacyclotetradecane> | 151191-04-7

• 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: 1,1'-<2,6-pyridylbis(methylene)>bis<4,8,11-tris(p-tolylsulfonyl)-1,4,8,11-tetraazacyclotetradecane>
• 英文别名: 1,1'-[2,6-Pyridinebis-(methylene)]-bis-tris-(p-toluenesulphonyl)-1,4,8,11-tetraazacyclotetradecane；1,4,8-Tris-(4-methylphenyl)sulfonyl-11-[[6-[[4,8,11-tris-(4-methylphenyl)sulfonyl-1,4,8,11-tetrazacyclotetradec-1-yl]methyl]pyridin-2-yl]methyl]-1,4,8,11-tetrazacyclotetradecane
• CAS: 151191-04-7
• 化学式: C₆₉H₈₉N₉O₁₂S₆
• 分子量: 1428.91
• InChiKey: XKUHELYBPSCOEW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.8
• 重原子数：
  96
• 可旋转键数：
  16
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  294
• 氢给体数：
  0
• 氢受体数：
  21

反应信息

• 作为反应物：
  描述：

  1,1'-<2,6-pyridylbis(methylene)>bis<4,8,11-tris(p-tolylsulfonyl)-1,4,8,11-tetraazacyclotetradecane> 在 氢溴酸 、 溶剂黄146 作用下， 以 水 为溶剂， 反应 48.0h， 以65%的产率得到1,1'-<2,6-pyridylbis(methylene)>bis<1,4,8,11-tetraazacyclotetradecane> octahydrobromide
  参考文献：
  名称：

  Linked cyclic polyamines with activity against hiv.

  摘要：

  揭示了一种药物组合物，其包含一种作为活性成分的一般式I的环链化合物，其中Z和Y分别是具有9至32个环成员和3至8个胺氮的环状多胺基团，这些胺氮在环中相距至少2个或更多个碳原子，A是芳香或杂芳基团，R和R'分别是取代或未取代的烷基链或含有杂原子的链，或其酸盐或金属络合物，与药用可接受的稀释剂或载体混合或结合。

  公开号：

  EP1223166A1
• 作为产物：
  描述：

  2,6-双(溴甲基)吡啶氢溴酸盐 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 22.0h， 以93%的产率得到1,1'-<2,6-pyridylbis(methylene)>bis<4,8,11-tris(p-tolylsulfonyl)-1,4,8,11-tetraazacyclotetradecane>
  参考文献：
  名称：

  Linked cyclic polyamines with activity against hiv.

  摘要：

  揭示了一种药物组合物，其包含一种作为活性成分的一般式I的环链化合物，其中Z和Y分别是具有9至32个环成员和3至8个胺氮的环状多胺基团，这些胺氮在环中相距至少2个或更多个碳原子，A是芳香或杂芳基团，R和R'分别是取代或未取代的烷基链或含有杂原子的链，或其酸盐或金属络合物，与药用可接受的稀释剂或载体混合或结合。

  公开号：

  EP1223166A1

文献信息

• Linked cyclic polyamines with activity against hiv.
  申请人：AnorMED Inc.

  公开号：EP1223166A1

  公开（公告）日：2002-07-17

  There is disclosed a pharmaceutical composition comprising as active ingredient a linked cyclic compound of general formula I,         Z - R - A - R' - Y     (I) in which Z and Y are independently cyclic polyamine moieties having from 9 to 32 ring members and from 3 to 8 amine nitrogens in the ring spaced by 2 or more carbon atoms from each other,    A is an aromatic or heteroaromatic moiety,    R and R' are each a substituted or unsubstituted alkylene chain or heteroatom containing chain. or an acid addition salt or metal complex thereof, in admixture or association with a pharmaceutically acceptable diluent or carrier.

  揭示了一种药物组合物，其包含一种作为活性成分的一般式I的环链化合物，其中Z和Y分别是具有9至32个环成员和3至8个胺氮的环状多胺基团，这些胺氮在环中相距至少2个或更多个碳原子，A是芳香或杂芳基团，R和R'分别是取代或未取代的烷基链或含有杂原子的链，或其酸盐或金属络合物，与药用可接受的稀释剂或载体混合或结合。
• Synthesis and Structure−Activity Relationships of Phenylenebis(methylene)- Linked Bis-tetraazamacrocycles That Inhibit Human Immunodeficiency Virus Replication. 2. Effect of Heteroaromatic Linkers on the Activity of Bicyclams
  作者：Gary J. Bridger、Renato T. Skerlj、Sreenivasan Padmanabhan、Stephen A. Martellucci、Geoffrey W. Henson、Michael J. Abrams、Heidi C. Joao、Myriam Witvrouw、Karen De Vreese、Rudi Pauwels、Erik De Clercq

  DOI：10.1021/jm950584t

  日期：1996.1.1

  A series of bicyclam analogs connected through a heteroaromatic linker have been synthesized and evaluated for their inhibitory effects on HIV-1 (IIIB) and HIV-2 (ROD) replication in MT-4 cells. The activity of pyridine- and pyrazine-linked bicyclams was found to be highly dependent upon the substitution of the heteroaromatic linker connecting the cyclam rings. For example, 2,6- and 3,5-pyridine-linked bicyclams were potent inhibitors of HIV-1 and HIV-2 replication, whereas the 2,5- and 2,4-substituted pyridine-linked compounds exhibited substantially reduced activity and, in addition, were found to be highly toxic to MT-4 cells. We have subsequently discovered that these effects are not unique; amino-substituted linkers also have the potential to deactivate phenylenebis(methylene)-linked bicyclams. A model is proposed to explain the deactivating effects of the pyridine group in certain substitution patterns based on the ability of the pyridine nitrogen to participate in pendant conformations (complexation) with the adjacent azamacrocyclic ring, which may involve hydrogen bonding or coordination to a transition metal. The introduction of a sterically hindering group such as phenyl at the 6-position of the 2,4-substituted pyridine-linked bicyclam appears to prevent pendant conformations, providing an analog with comparable anti-HIV-1 and anti-HIV-2 activities to the parent m-phenylenebis(methylene)-linked bicyclam, The results of this study have been used to develop a quantitative structure-activity relationship model with improved predictive capability in order to aid the design of antiviral bis-azamacrocyclic analogs.