二氯脱氢松香酸 | 65281-77-8

• 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
• 中文名称: 二氯脱氢松香酸
• 英文名称: 12,14-Dichlorodehydroabietic acid
• 英文别名: (1R,4aS,10aR)-6,8-dichloro-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthrene-1-carboxylic acid
• CAS: 65281-77-8
• 化学式: C₂₀H₂₆Cl₂O₂
• 分子量: 369.331
• InChiKey: RKQWIQSTFSBVMQ-CDHQVMDDSA-N

物化性质

• 熔点：
  222 - 237°C
• 沸点：
  469.6±45.0 °C(Predicted)
• 密度：
  1.200±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

制备方法与用途

生物活性

12,14-二氯去氢松香酸（12,14-Dichlorodehydroabietic acid）是一种有效的Ca²⁺激活K⁺ (BK) 通道开启剂。它能够阻止哺乳动物大脑中GABA依赖的氯离子内流，并作为非竞争性 GABAA 拮抗剂发挥作用。此外，12,14-二氯去氢松香酸还能增加细胞内游离Ca²⁺含量，促进递质释放。

靶点

• Ca²⁺激活K⁺ (BK) 通道
• GABA_A

反应信息

• 作为反应物：
  描述：

  二氯脱氢松香酸 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 甲醇 、 乙醚 、 乙醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 145.08h， 生成 1,3-bis[[5-(12,14-dichloro-13-isopropyl-8,11a-dimethyl-8-methoxycarbonyl-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：

  脱氢松香酸 在 氯 作用下， 以 四氯化碳 为溶剂， 反应 1.5h， 以39%的产率得到二氯脱氢松香酸
  参考文献：
  名称：

  基于己二烯二萜衍生物肟化的BK通道开放剂的设计，合成和表征

  摘要：

  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。

  DOI：

  10.1016/j.bmc.2010.09.072

文献信息

• 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.
• Dehydroabietic acid derivatives as a novel scaffold for large-Conductance calcium-Activated K+ channel openers
  作者：Tomohiko Ohwada、Taro Nonomura、Keisuke Maki、Kazuho Sakamoto、Susumu Ohya、Katsuhiko Muraki、Yuji Imaizumi

  DOI：10.1016/j.bmcl.2003.08.072

  日期：2003.11

  We found that the dehydroabietic acid structure is a new scaffold for chemical modulators of large-conductance calcium-activated K+ channels (BK channels). Structure-activity relationship (SAR) studies of the dehydroabietic acid derivatives and related non-aromatic compounds such as pimaric acid revealed the importance of the carboxyl functionality and an appropriate hydrophobic moiety of the molecules for BK channel-opening ability. (C) 2003 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：——
• LEE, HING-BIU;PEART, THOMAS E.;CARRON, JOHN M., J. CHROMATOGR., 498,(1990) N, C. 367-379
  作者：LEE, HING-BIU、PEART, THOMAS E.、CARRON, JOHN M.

  DOI：——

  日期：——
• US7385083B2
  申请人：——

  公开号：US7385083B2

  公开（公告）日：2008-06-10