1-Benzo[b][1]benzazepin-11-yl-6-bromohexan-1-one | 316362-97-7

• 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: 1-Benzo[b][1]benzazepin-11-yl-6-bromohexan-1-one
• CAS: 316362-97-7
• 化学式: C₂₀H₂₀BrNO
• 分子量: 370.289
• InChiKey: QYPZBIFZJQQKNV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  potassium 4-benzoylphenolate 、 1-Benzo[b][1]benzazepin-11-yl-6-bromohexan-1-one 生成 6-(4-Benzoyl-phenoxy)-1-dibenzo[b,f]azepin-5-yl-hexan-1-one
  参考文献：
  名称：

  Triplet energy transfer of the intramolecular system having benzophenone and dibenz[b,f]azepine at the chain ends: chain length dependence

  摘要：

  Intramolecular triplet-triplet energy transfer in a series of polymethylene chains having a benzophenone (BP) group as an energy donor and a dibenz[b,f]azepine (DBA) group as an energy acceptor (BP-O(CH2)nCO-DBA) has been studied by phosphorescence measurement and nanosecond laser photolysis. In a rigid solution and PMMA matrix, the quantum yield of triplet-triplet energy transfer is close to unity for the chain lengths shorter than n = 5. On the basis of the through-space mechanism of energy transfer, phosphorescence decay curves were analyzed by Dexter's equation in which the distribution of donor-acceptor distance was calculated by the conformational energy analysis. The results of the simulation were in fairly good agreement with the experimentally observed decay curves. The rate constant of triplet-triplet energy transfer is strongly dependent on the chain length, i.e., about one-tenth decrease per every methylene unit, and the rate is much smaller than that of singlet-singlet energy transfer.

  DOI：

  10.1021/j100162a009
• 作为产物：
  描述：

  亚氨基芪 、 6-溴己酰氯 在 N,N-二甲基苯胺 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以96%的产率得到1-Benzo[b][1]benzazepin-11-yl-6-bromohexan-1-one
  参考文献：
  名称：

  Synthesis of New Cardioselective M2 Muscarinic Receptor Antagonists.

  摘要：

  一系列5H-二苯[b, f]氮杂环戊烯衍生物被合成并评估其对体外毒蕈碱受体的结合亲和力。在这些化合物中，化合物8对人重组M2受体表现出高亲和力（Ki=2.6 nM），对M4受体的亲和力较低（比M2受体低39倍），对M1和M3受体的亲和力非常低（分别比M2受体低119倍和112倍）。化合物8的高M2选择性可能归因于氮杂环上的烯键。功能实验表明，8是一个竞争性拮抗剂，对心脏的亲和力较高（pA2=7.1），而对肠道毒蕈碱受体的亲和力较低（IC50=0.54 μM）。体内实验确认了8的体外M2选择性。经过静脉注射和十二指肠内给药后，乙酰胆碱诱导的心动过缓在大鼠中呈剂量依赖性被拮抗。在大鼠中，介导M1或M3受体的胆碱能功能（唾液分泌、瞳孔直径、胃排空、肠道转运时间）在口服给药8的情况下未受到影响，即使在高达抗心动过缓有效剂量30倍的剂量下。此外，8在小鼠中没有镇痛活性，表明其对中枢神经系统的穿透性差。在犬中，口服给药后夜间心动过缓呈剂量依赖性抑制，作用持续约24小时。化合物8似乎是一种有前途的心脏选择性抗毒蕈碱药物，可用于治疗心脏传导系统的功能障碍，如窦性或结性心动过缓（“病态窦综合征”）和房室传导阻滞。

  DOI：

  10.1248/cpb.48.1611

文献信息

• Synthesis of New Cardioselective M2 Muscarinic Receptor Antagonists.
  作者：Giacomina R. MANDELLI、Stefano MAIORANA、Patrizia TERNI、Giuseppina LAMPERTI、Maria Luisa COLIBRETTI、Bruno P. IMBIMBO

  DOI：10.1248/cpb.48.1611

  日期：——

  A series of 5H-dibenz[b, f]azepine derivatives was prepared and evaluated for binding affinities to muscarinic receptors in vitro. Among them, compound 8 showed a high affinity for human recombinant M2 receptors (Ki=2.6 nM), a low affinity for M4 receptors (39-fold less than for M2 receptors) and a very low affinity for M1 and M3 receptors (119- and 112-fold less than for M2 receptors, respectively). The high M2 selectivity of 8 may be attributed to the olefinic bond of the azepine ring. Functional experiments showed 8 to be a competitive antagonist with high affinity to the cardiac (pA2=7.1) and low affinity to the intestinal muscarinic receptors (IC50=0.54 μM). In vivo experiments confirmed the in vitro M2 selectivity of 8. Acetylcholine-induced bradycardia was dose-dependently antagonized in rats after both intravenous and intraduodenal administration of 8. In rats, cholinergic functions mediated by M1 or M3 receptors (salivary secretion, pupil diameter, gastric emptying, intestinal transit time) were not affected by the oral administration of 8 even at doses as high as 30 times the antibradycardic effective dose. Furthermore, 8 had no analgesic activity in mice, indicating poor central nervous system penetration. In dogs, nocturnal bradycardia was dose-dependently inhibited by the oral route with a duration of action of about 24 h. Compound 8 appears to be a promising cardioselective antimuscarinic agent for the treatment of dysfunctions of the cardiac conduction system such as sinus or nodal bradycardia ("sick-sinus syndrome") and atrioventricular block.

  一系列5H-二苯[b, f]氮杂环戊烯衍生物被合成并评估其对体外毒蕈碱受体的结合亲和力。在这些化合物中，化合物8对人重组M2受体表现出高亲和力（Ki=2.6 nM），对M4受体的亲和力较低（比M2受体低39倍），对M1和M3受体的亲和力非常低（分别比M2受体低119倍和112倍）。化合物8的高M2选择性可能归因于氮杂环上的烯键。功能实验表明，8是一个竞争性拮抗剂，对心脏的亲和力较高（pA2=7.1），而对肠道毒蕈碱受体的亲和力较低（IC50=0.54 μM）。体内实验确认了8的体外M2选择性。经过静脉注射和十二指肠内给药后，乙酰胆碱诱导的心动过缓在大鼠中呈剂量依赖性被拮抗。在大鼠中，介导M1或M3受体的胆碱能功能（唾液分泌、瞳孔直径、胃排空、肠道转运时间）在口服给药8的情况下未受到影响，即使在高达抗心动过缓有效剂量30倍的剂量下。此外，8在小鼠中没有镇痛活性，表明其对中枢神经系统的穿透性差。在犬中，口服给药后夜间心动过缓呈剂量依赖性抑制，作用持续约24小时。化合物8似乎是一种有前途的心脏选择性抗毒蕈碱药物，可用于治疗心脏传导系统的功能障碍，如窦性或结性心动过缓（“病态窦综合征”）和房室传导阻滞。
• Triplet energy transfer of the intramolecular system having benzophenone and dibenz[b,f]azepine at the chain ends: chain length dependence
  作者：Hideaki Katayama、Shogo Maruyama、Shinzaburo Ito、Yoshinobu Tsujii、Akira Tsuchida、Masahide Yamamoto

  DOI：10.1021/j100162a009

  日期：1991.5

  Intramolecular triplet-triplet energy transfer in a series of polymethylene chains having a benzophenone (BP) group as an energy donor and a dibenz[b,f]azepine (DBA) group as an energy acceptor (BP-O(CH2)nCO-DBA) has been studied by phosphorescence measurement and nanosecond laser photolysis. In a rigid solution and PMMA matrix, the quantum yield of triplet-triplet energy transfer is close to unity for the chain lengths shorter than n = 5. On the basis of the through-space mechanism of energy transfer, phosphorescence decay curves were analyzed by Dexter's equation in which the distribution of donor-acceptor distance was calculated by the conformational energy analysis. The results of the simulation were in fairly good agreement with the experimentally observed decay curves. The rate constant of triplet-triplet energy transfer is strongly dependent on the chain length, i.e., about one-tenth decrease per every methylene unit, and the rate is much smaller than that of singlet-singlet energy transfer.