trans(6a-H,10a-H)-cis(10a-H,11-H)-11-amino-6,6a,7,8,9,10,10a,11-octahydrodibenzoxepine | 130933-29-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噁庚英
• 英文名称: trans(6a-H,10a-H)-cis(10a-H,11-H)-11-amino-6,6a,7,8,9,10,10a,11-octahydrodibenzoxepine
• 英文别名: (6aR,10aR,11R)-6,6a,7,8,9,10,10a,11-octahydrobenzo[c][1]benzoxepin-11-amine
• CAS: 130933-29-8
• 化学式: C₁₄H₁₉NO
• 分子量: 217.311
• InChiKey: ZPXCDCQGDGAVNJ-MISXGVKJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  35.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  trans(6a-H,10a-H)-cis(10a-H,11-H)-11-amino-6,6a,7,8,9,10,10a,11-octahydrodibenzoxepine 、 4-<4-(4-fluorophenyl)-1-piperazinyl>butyric acid 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 4-[4-(4-Fluoro-phenyl)-piperazin-1-yl]-N-(6aS,10aS,11S)-6,6a,7,8,9,10,10a,11-octahydro-dibenzo[b,e]oxepin-11-yl-butyramide
  参考文献：
  名称：

  A new class of calcium antagonists. Synthesis and biological activity of 11-[(.omega.-aminoalkanoyl)amino]-6,6a,7,8,9,10,10a,11-octahydrodibenzo[b,e]thiepin derivatives

  摘要：

  A series of 11-[(omega-aminoalkanoyl)amino]-6,6a,7,8,9,10,10a,11?? -octahydrodibenzo[b,e]thiepin derivatives were prepared and found to be a structurally new class of calcium antagonists. The structure-activity relationship studies indicated that the optimum was (6aR*, 10aR*, 11R*)-11-[[4-[4-(4-fluorophenyl)-1-piperazinyl]butyryl]amino]-6,6a7,8,9,10,10a,11-octahydrodibenzo[b,e]thiepin (31, pA2 8.16), which was superior to diltiazem (pA2 7.42) in calcium antagonistic activity. Compound 31 showed antihypertensive activity in anesthetized rats, without a significant effect on the heart rate. It had also antianginal effects in vasopressin-induced ST-depression and methacholine-induced ST-elevation testings in rats. These potencies of 31 were essentially equal to those of diltiazem.

  DOI：

  10.1021/jm00106a019
• 作为产物：
  描述：

  trans-6a-H,10a-H-6,6a,7,8,9,10,10a,11-octahydro-11-hydroxydibenzooxepin 在 氯化亚砜 、 氨 作用下， 以 二氯甲烷 为溶剂， 反应 73.5h， 生成 trans(6a-H,10a-H)-cis(10a-H,11-H)-11-amino-6,6a,7,8,9,10,10a,11-octahydrodibenzoxepine
  参考文献：
  名称：

  Synthesis and Stereochemistry of 11-Amino-6,6a,7,8.8.10,10a,11-octahydrodibenzo(b,e)thiepines and -oxepines.

  摘要：

  11-氨基-6、6a、7、8、9、10、10a、11-八氢二苯并[b，e]硫杂卓(6a-d)和-氧杂卓(7a-d)通过 6、6a、7、8、9、10、10a、11-八氢-11-氧二苯并[b，e]硫杂卓(1a，b)和-氧杂卓(2a，b)的 Leuckart 反应合成、10、10a、11-八氢-11-氧代二苯并[b，e]硫杂卓 (1a, b) 和-氧杂卓 (2a, b) 通过 Leuckart 反应合成，然后分别水解反应产物 4a-d 和 5a-d。四种非对映异构体，即顺式（6a-H，10a-H）-顺式（10a-H，11-H）6a 和 7a、顺式（6a-H，10a-H）-反式（10a-H，11-H）6b 和 7b、反式（6a-H，10a-H）-反式（10a-H，11a-H）6c 和 7c，以及反式（6a-H，10a-H）-顺式（10a-H、11-H）6d 和 7d，并通过化学方法以及 1H 核磁共振光谱和 X 射线晶体学分析阐明了它们的构型和构象。

  DOI：

  10.1248/cpb.40.2270

文献信息

• A new class of calcium antagonists. Synthesis and biological activity of 11-[(.omega.-aminoalkanoyl)amino]-6,6a,7,8,9,10,10a,11-octahydrodibenzo[b,e]thiepin derivatives
  作者：Mikio Kurokawa、Fuminori Sato、Naonobu Hatano、Yayoi Honda、Hitoshi Uno

  DOI：10.1021/jm00106a019

  日期：1991.2

  A series of 11-[(omega-aminoalkanoyl)amino]-6,6a,7,8,9,10,10a,11?? -octahydrodibenzo[b,e]thiepin derivatives were prepared and found to be a structurally new class of calcium antagonists. The structure-activity relationship studies indicated that the optimum was (6aR*, 10aR*, 11R*)-11-[[4-[4-(4-fluorophenyl)-1-piperazinyl]butyryl]amino]-6,6a7,8,9,10,10a,11-octahydrodibenzo[b,e]thiepin (31, pA2 8.16), which was superior to diltiazem (pA2 7.42) in calcium antagonistic activity. Compound 31 showed antihypertensive activity in anesthetized rats, without a significant effect on the heart rate. It had also antianginal effects in vasopressin-induced ST-depression and methacholine-induced ST-elevation testings in rats. These potencies of 31 were essentially equal to those of diltiazem.
• Synthesis and Stereochemistry of 11-Amino-6,6a,7,8.8.10,10a,11-octahydrodibenzo(b,e)thiepines and -oxepines.
  作者：Mikio KUROKAWA、Akira ITOGAWA、Jun-ichi MATAUMOTO、Yoshihisa FUKUMOTO、Tomitake TSUKIHARA

  DOI：10.1248/cpb.40.2270

  日期：——

  11-Amino-6, 6a, 7, 8, 9, 10, 10a, 11-octahydrodibebenzo[b, e]thiepines (6a-d) and -oxepines (7a-d) were synthesized by the Leuckart reaction of 6, 6a, 7, 8, 9, 10, 10a, 11-octahydro-11-oxodibenzo[b, e]thiepines (1a, b)and -oxepines (2a, b) followed by hydrolysis of the reaction products 4a-d and 5a-d, respectively. The four diastereomers, cis(6a-H, 10a-H)-cis(10a-H, 11-H) 6a and 7a, cis(6a-H, 10a-H)-trans(10a-H, 11-H) 6b and 7b, trans(6a-H, 10a-H)-trans(10a-H, 11a-H)6c and 7c, and trans(6a-H, 10a-H)-cis(10a-H, 11-H) 6d and 7d, were isolated and their configurations and conformations were elucidated by chemical methods together with 1H-nuclear magnetic resonance spectroscopic and X-ray crystallographic analyses.

  11-氨基-6、6a、7、8、9、10、10a、11-八氢二苯并[b，e]硫杂卓(6a-d)和-氧杂卓(7a-d)通过 6、6a、7、8、9、10、10a、11-八氢-11-氧二苯并[b，e]硫杂卓(1a，b)和-氧杂卓(2a，b)的 Leuckart 反应合成、10、10a、11-八氢-11-氧代二苯并[b，e]硫杂卓 (1a, b) 和-氧杂卓 (2a, b) 通过 Leuckart 反应合成，然后分别水解反应产物 4a-d 和 5a-d。四种非对映异构体，即顺式（6a-H，10a-H）-顺式（10a-H，11-H）6a 和 7a、顺式（6a-H，10a-H）-反式（10a-H，11-H）6b 和 7b、反式（6a-H，10a-H）-反式（10a-H，11a-H）6c 和 7c，以及反式（6a-H，10a-H）-顺式（10a-H、11-H）6d 和 7d，并通过化学方法以及 1H 核磁共振光谱和 X 射线晶体学分析阐明了它们的构型和构象。