(3R-cis)-3-(acetyloxy)-1,3,4,5-tetrahydro-4-(4-methoxyphenyl)-1-[2-(methylamino)ethyl]-6-(trifluoromethyl)-2H-1-benzazepin-2-one | 132201-65-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: (3R-cis)-3-(acetyloxy)-1,3,4,5-tetrahydro-4-(4-methoxyphenyl)-1-[2-(methylamino)ethyl]-6-(trifluoromethyl)-2H-1-benzazepin-2-one
• 英文别名: Acetic acid 4-(4-methoxy-phenyl)-1-(2-methylamino-ethyl)-2-oxo-6-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-3-yl ester；[(3R,4S)-4-(4-methoxyphenyl)-1-[2-(methylamino)ethyl]-2-oxo-6-(trifluoromethyl)-4,5-dihydro-3H-1-benzazepin-3-yl] acetate
• CAS: 132201-65-1
• 化学式: C₂₃H₂₅F₃N₂O₄
• 分子量: 450.458
• InChiKey: VTEAXXWOUVPHFD-LAUBAEHRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (3R-cis)-3-(acetyloxy)-1,3,4,5-tetrahydro-4-(4-methoxyphenyl)-1-[2-(methylamino)ethyl]-6-(trifluoromethyl)-2H-1-benzazepin-2-one 在 三溴化硼 作用下， 生成 (3R,4S)-3-Hydroxy-4-(4-hydroxy-phenyl)-1-(2-methylamino-ethyl)-6-trifluoromethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-one
  参考文献：
  名称：

  Benzazepinone calcium channel blockers. 4. Structure-activity overview and intracellular binding site

  摘要：

  We have synthesized a series of benzazepinones (2) in order to determine the structure-activity relationships (SAR) for calcium channel blockers related to diltiazem. A prerequisite for calcium channel blocking activity in vitro and in vivo is the presence of two pharmacophores: a 4'-aryl methyl ether and a basic substituent appended to N1 with a pK(a) in the physiological range. When these constraints are satisfied, a wide variety of substitution is tolerated at C6, C7, and C3. The presence of an electron-withdrawing group at C6 appears to enhance potency in vitro and in vivo. For such benzazepinones, activity is primarily dependent upon lipophilicity, as measured by log P. We believe these compounds must partition into the cell membrane in order to access their receptor. The quaternary methiodide 15k was used to demonstrate that the binding site for benzazepinones is on the intracellular face of the membrane. This work represents the first comprehensive SAR of diltiazem-like calcium channel blockers.

  DOI：

  10.1021/jm00082a020
• 作为产物：
  描述：

  Acetic acid (3R,4S)-4-(4-methoxy-phenyl)-1-{2-[methyl-(2,2,2-trichloro-ethoxycarbonyl)-amino]-ethyl}-2-oxo-6-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-3-yl ester 在 溶剂黄146 、 锌 作用下， 反应 26.0h， 生成 (3R-cis)-3-(acetyloxy)-1,3,4,5-tetrahydro-4-(4-methoxyphenyl)-1-[2-(methylamino)ethyl]-6-(trifluoromethyl)-2H-1-benzazepin-2-one
  参考文献：
  名称：

  苯并ze庚酮钙通道阻滞剂。2.结构活性和药物代谢研究导致有效的降压药。与苯并噻嗪酮的比较。

  摘要：

  作为发现地尔硫卓有效降压类似物的程序的一部分，我们制备了1-benzazepin-2-ones（4）。苯并ze庚因酮竞争性地取代了放射性标记的地尔硫卓，并在钙通道受体蛋白上表现出相同的绝对立体化学偏好。在稠合的芳族环中含有三氟甲基取代基的4的衍生物表现出有效的长效降压活性。对4的代谢的研究导致了代谢稳定的降压钙通道阻滞剂5a和5c。与第二代地尔硫卓类似物TA-3090（3e）相比，苯并ze庚酮5a是更长效且更有效的降压药。

  DOI：

  10.1021/jm00082a018

文献信息

• Benzazepine derivatives
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US04952692A1

  公开（公告）日：1990-08-28

  Novel compounds of the formula ##STR1## exhibit calcium channel blocking activity and are useful as cardiovascular agents.

  公式为##STR1##的新化合物具有钙通道阻滞活性，可用作心血管药物。
• Method for inhibiting loss of cognitive functions employing a calcium channel blocker alone or in combination with an ace inhibitor
  申请人：E.R. SQUIBB & SONS, INC.

  公开号：EP0344995A2

  公开（公告）日：1989-12-06

  A method is provided for inhibiting loss of cognitive function, including memory, which may or may not be associated with Alzheimer's disease, in a mammalian species by administering a benzazepine-type calcium channel blocker such as diltiazem, SQ 31,765 or SQ 32,324 alone or in combination with an ACE inhibitor, such as captopril or SQ 29,852, over a prolonged period of treatment.

  本发明提供了一种用于抑制哺乳动物认知功能（包括记忆力）丧失的方法，这种丧失可能与阿尔茨海默病有关，也可能与阿尔茨海默病无关，其方法是通过单独或与 ACE 抑制剂（如卡托普利或 SQ 29 852）联合长期服用苯并氮杂卓类钙通道阻滞剂，如地尔硫卓、SQ 31,765 或 SQ 32,324。
• Combination of a calcium channel blocker and thromboxane A2 receptor antagonist or synthetase inhibitor and method for treating ischemia employing such combination
  申请人：E.R. SQUIBB & SONS, INC.

  公开号：EP0351755A1

  公开（公告）日：1990-01-24

  A method is provided for treating ischemia in a mammalian species by administering a combination of a calcium channel blocker such as diltiazem, SQ 31,765 or SQ 32,324 and a thromboxane A2 receptor antagonist such as SQ 30,741 or a thromboxane synthetase inhibitor such as dazoxiben.

  本发明提供了一种治疗哺乳动物缺血的方法，即给药钙通道阻滞剂如地尔硫卓、SQ 31,765 或 SQ 32,324 和血栓素 A2 受体拮抗剂如 SQ 30,741 或血栓素合成酶抑制剂如达唑西本的组合。
• Use of a calcium channel blocker for preventing or treating anxiety
  申请人：E.R. Squibb & Sons, Inc.

  公开号：EP0400665A2

  公开（公告）日：1990-12-05

  The use of a calcium channel blocker such as diltiazem or nifedipine for inhibiting onset of or treating anxiety over a prolonged period of treatment is provided.

  提供了使用地尔硫卓或硝苯地平等钙通道阻滞剂抑制焦虑症发病或治疗焦虑症的长期治疗方法。
• FLOYD, DAVID;KRAPCHO, JOHN
  作者：FLOYD, DAVID、KRAPCHO, JOHN

  DOI：——

  日期：——