12,14-dichloro-13-isopropyl-8,11a-dimethyl-6-oxo-5-[5-(4-iodophenyl)pent-4-ynyl]-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[b,d]azepine-8-carboxylic acid methyl ester | 915151-02-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 12,14-dichloro-13-isopropyl-8,11a-dimethyl-6-oxo-5-[5-(4-iodophenyl)pent-4-ynyl]-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[b,d]azepine-8-carboxylic acid methyl ester
• CAS: 915151-02-9
• 化学式: C₃₂H₃₆Cl₂INO₃
• 分子量: 680.453
• InChiKey: OEZULPXVKGSTMV-ZIIROOFJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.53
• 重原子数：
  39.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  46.61
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  12,14-dichloro-13-isopropyl-8,11a-dimethyl-6-oxo-5-[5-(4-iodophenyl)pent-4-ynyl]-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[b,d]azepine-8-carboxylic acid methyl ester 在 bis-triphenylphosphine-palladium(II) chloride 氢氧化钾 、 copper(l) iodide 、 18-冠醚-6 、 三乙胺 作用下， 以 甲醇 为溶剂， 反应 91.0h， 生成 1,4-bis[[5-(12,14-dichloro-13-isopropyl-8,11a-dimethyl-8-hydroxycarbonyl-6-oxo-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[b,d]azepin-5-yl)]pent-1-ynyl]benzene
  参考文献：
  名称：

  Design, synthesis, and BK channel-opening activity of hexahydrodibenzazepinone derivatives

  摘要：

  In order to explore new scaffolds for large-conductance Ca2+ -activated K+ channel (BK channel) openers, we carried out molecular design and synthesis on the basis of the following two concepts: (1) introduction of a heteroatom into the dehydroabietic acid (BK channel opener) skeleton would allow easier introduction of substituents. (2) Because of the fourfold symmetrical structure of BK channels, dimeric compounds in which two pharmacophores are linked through a tether are expected to have a greater binding probability to the channels, resulting in increased channel-opening activity. Herein, we explore the usefulness of the hexahydrodibenzazepinone structure as a new scaffold for BK channel openers. The synthesized monomer compounds of hexahydrodibenzazepinone derivatives, which can be derived from dehydroabietic acid, were subjected to electrophysiological patch-clamp studies, followed by Magnus contraction-relaxation assay using rabbit urinary bladder smooth muscle strips to assess overall activities. Dimeric compounds were designed by linking the monomeric hexahydrodibenzazepinone derivatives through a diacetylenebenzene tether, and their channel-opening activities were evaluated by electrophysiological methods. Finally, we concluded that the critical structure for BK channel-opening activity is the hexahydrodibenzazepin one monomer substituted with a phenyl-bearing alkynyl substituent on the lactam amide. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.07.042
• 作为产物：
  描述：

  12,14-dichlorodehydroabietic acid methyl ester 在 bis-triphenylphosphine-palladium(II) chloride 吡啶 、 chromium(VI) oxide 、 copper(l) iodide 、 盐酸羟胺 、 乙酸酐 、 sodium hydride 、 溶剂黄146 、 三乙胺 、 三氟乙酸 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 86.5h， 生成 12,14-dichloro-13-isopropyl-8,11a-dimethyl-6-oxo-5-[5-(4-iodophenyl)pent-4-ynyl]-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[b,d]azepine-8-carboxylic acid methyl ester
  参考文献：
  名称：

  Design, synthesis, and BK channel-opening activity of hexahydrodibenzazepinone derivatives

  摘要：

  In order to explore new scaffolds for large-conductance Ca2+ -activated K+ channel (BK channel) openers, we carried out molecular design and synthesis on the basis of the following two concepts: (1) introduction of a heteroatom into the dehydroabietic acid (BK channel opener) skeleton would allow easier introduction of substituents. (2) Because of the fourfold symmetrical structure of BK channels, dimeric compounds in which two pharmacophores are linked through a tether are expected to have a greater binding probability to the channels, resulting in increased channel-opening activity. Herein, we explore the usefulness of the hexahydrodibenzazepinone structure as a new scaffold for BK channel openers. The synthesized monomer compounds of hexahydrodibenzazepinone derivatives, which can be derived from dehydroabietic acid, were subjected to electrophysiological patch-clamp studies, followed by Magnus contraction-relaxation assay using rabbit urinary bladder smooth muscle strips to assess overall activities. Dimeric compounds were designed by linking the monomeric hexahydrodibenzazepinone derivatives through a diacetylenebenzene tether, and their channel-opening activities were evaluated by electrophysiological methods. Finally, we concluded that the critical structure for BK channel-opening activity is the hexahydrodibenzazepin one monomer substituted with a phenyl-bearing alkynyl substituent on the lactam amide. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.07.042