12,14-dichlorodehydroabietic acid methyl ester | 915150-85-5

• 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-dichlorodehydroabietic acid methyl ester
• 英文别名: methyl (1R,4aS,10aR)-6,8-dichloro-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthrene-1-carboxylate
• CAS: 915150-85-5
• 化学式: C₂₁H₂₈Cl₂O₂
• 分子量: 383.358
• InChiKey: JBCWLELYEDSKOH-MAODMQOUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  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 96.5h， 生成 12,14-dichloro-13-isopropyl-8,11a-dimethyl-6-oxo-5-[5-(3-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
• 作为产物：
  描述：

  脱氢松香酸 在 氯 、 三氯化铁 作用下， 以 四氯化碳 、 乙醚 为溶剂， 生成 12,14-dichlorodehydroabietic acid methyl ester
  参考文献：
  名称：

  Thakore,A.N.; Oehlschlager,A.C., Canadian Journal of Chemistry, 1977, vol. 55, p. 3298 - 3303

  摘要：

  DOI：

文献信息

• Design, synthesis, and characterization of BK channel openers based on oximation of abietane diterpene derivatives
  作者：Yong-Mei Cui、Eriko Yasutomi、Yuko Otani、Katsutoshi Ido、Takashi Yoshinaga、Kohei Sawada、Tomohiko Ohwada

  DOI：10.1016/j.bmc.2010.09.072

  日期：2010.12

  ether derivatives at the benzylic position of unsubstituted, dichloro, trichloro, and monobromo derivatives of the aromatic C-ring of dehydroabietic acid and podocarpic acid were synthesized and evaluated as BK channel openers in an assay system of CHO-K1 cells expressing hBKα channels. Detailed SAR analysis showed that the oximation was particularly effective in the cases of dehydroabietic acid derivatives

  合成了脱氢松香酸和罗汉果酸的芳香C环的未取代，二氯，三氯和一溴衍生物的苄基位置上的肟醚衍生物，并在表达hBKα通道的CHO-K1细胞分析系统中将其作为BK通道开放剂进行评估。详细的SAR分析表明，在脱氢松香酸衍生物的情况下，肟化作用特别有效，并且这些肟衍生物中的一些表现出比标准化合物NS1619更有效的BK通道活性。本研究为开发有效的BK通道开放剂提供了新的结构基础。
• Novel oxime and oxime ether derivatives of 12,14-dichlorodehydroabietic acid: Design, synthesis, and BK channel-opening activity
  作者：Yong-Mei Cui、Eriko Yasutomi、Yuko Otani、Takashi Yoshinaga、Katsutoshi Ido、Kohei Sawada、Masatoshi Kawahata、Kentaro Yamaguchi、Tomohiko Ohwada

  DOI：10.1016/j.bmcl.2008.10.078

  日期：2008.12

  Oxime ether derivatives of the benzylic ketone of 12,14-dichlorodehydroabietic acid (diCl-DHAA, 4b) were synthesised, and their BK channel-opening activity was evaluated in an assay system of CHO-K1 cells expressing hBK alpha channels. Oxime ether structure on the B ring of diCl-DHAA significantly increased the BK channel-opening activity. (C) 2008 Elsevier Ltd. All rights reserved.
• Thakore,A.N.; Oehlschlager,A.C., Canadian Journal of Chemistry, 1977, vol. 55, p. 3298 - 3303
  作者：Thakore,A.N.、Oehlschlager,A.C.

  DOI：——

  日期：——
• Design, synthesis, and BK channel-opening activity of hexahydrodibenzazepinone derivatives
  作者：Toshihiko Tashima、Yoshimi Toriumi、Yumi Mochizuki、Taro Nonomura、Satoru Nagaoka、Katsuo Furukawa、Hiromichi Tsuru、Satomi Adachi-Akahane、Tomohiko Ohwada

  DOI：10.1016/j.bmc.2006.07.042

  日期：2006.12

  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.