2-氯-1-(10,11-二氢二苯并[B,F]氮杂平-5-基)-乙酮 | 3534-05-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 中文名称: 2-氯-1-(10,11-二氢二苯并[B,F]氮杂平-5-基)-乙酮
• 中文别名: 5-氯乙酰基-亚氨基二苄
• 英文名称: 2-chloro-1-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)ethan-1-one
• 英文别名: 5-chloroacetyl-10,11-dihydro-5H-dibenzazepine；5-chloroacetyl-10,11-dihydro-5H-dibenzo[b,f]azepine；5-chloroacetyl-10,11-dihydro-5H-dibenz[b,f]azepine；5-Chloracetyl-10,11-dihydro-5H-dibenz[b,f]azepin；10,11-Dihydro-5-(chloracetyl)-5H-dibenz azepin；5-Chloracetyl-10,11-dihydro-5H-dibenzazepin；5-(Chloroacetyl)-10,11-dihydro-5H-dibenzo[b,f]azepine；2-chloro-1-(5,6-dihydrobenzo[b][1]benzazepin-11-yl)ethanone
• CAS: 3534-05-2
• 化学式: C₁₆H₁₄ClNO
• mdl: MFCD00250086
• 分子量: 271.746
• InChiKey: TXCPQCCKJNJBJU-UHFFFAOYSA-N

物化性质

• 熔点：
  97-100 °C
• 沸点：
  474.8±44.0 °C(Predicted)
• 密度：
  1.249±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.187
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  N-甲基哌嗪 、 2-氯-1-(10,11-二氢二苯并[B,F]氮杂平-5-基)-乙酮 在 sodium carbonate 作用下， 以 乙醇 为溶剂， 反应 5.0h， 以84%的产率得到5-(2-(4-methyl-1-piperazinyl)acetyl)-10,11-dihydro-5H-dibenzazepine
  参考文献：
  名称：

  Tricyclic compounds as selective antimuscarinics. 1. Structural requirements for selectivity towards the muscarinic acetylcholine receptor in a series of pirenzepine and imipramine analogs

  摘要：

  The M1-selective antiulcer drug pirenzepine (1) is a tricyclic compound with close resemblance to tricyclic psychotropic agents such as imipramine (2). Despite this fact, pirenzepine is devoid of any psychotropic effects, exhibiting measurable antagonistic effects in biochemical assays and receptor binding studies only toward the muscarinic receptor system. To understand how different groups in these tricyclic molecules affect binding affinities, a set of nine compounds structurally related to pirenzepine (1) and imipramine (2) has been selected for analysis, comprising three different tricycles and three different side chains. The compounds were tested for their affinity to the imipramine and muscarinic receptors in homogenized rat cortex tissue. The result of these studies suggests that it is the nature and placement of accessory groups that determine the differences in receptor recognition and the binding process. In the case of pirenzepine (1), preferential binding toward the muscarinic receptor is brought about by the endocyclic amide group, by the positioning of the protonated N atom of the side chain, and to a minor extent by the exocyclic amide group. From these findings a putative model for the explanation of selective binding of pirenzepine (1) to the muscarinic receptor has been derived.

  DOI：

  10.1021/jm00391a019
• 作为产物：
  描述：

  亚氨基二苄 、 氯乙酰氯 以 甲苯 为溶剂， 以73 %的产率得到2-氯-1-(10,11-二氢二苯并[B,F]氮杂平-5-基)-乙酮
  参考文献：
  名称：

  具有新反应基团的 SARS-CoV-2 3C 样蛋白酶抑制剂的发现及机制研究

  摘要：

  3CL pro是治疗 COVID-19 的一个有吸引力的靶点。使用支架跳跃策略，我们鉴定了 3CL pro ( 3a )的有效抑制剂，其含有硫氰酸盐部分作为新型弹头，可以与蛋白质的 Cys145 形成共价键。串联质谱 (MS/MS) 和 X 射线晶体学证实了3a与其催化口袋中的蛋白质之间形成共价键的机制。此外，还设计并合成了化合物3a的几种类似物。其中，化合物3h对3CL pro的抑制效果最好，IC 50为0.322 μM，k inact / K i值为1669.34 M –1 s –1，并且对3CL pro对宿主蛋白酶表现出良好的靶点选择性。化合物3c可抑制 Vero E6 细胞中的 SARS-CoV-2 (EC 50 = 2.499 μM)，且细胞毒性较低 (CC 50 > 200 μM)。这些研究为未来探索和开发新的 3CL前体抑制剂提供了思路和见解。

  DOI：

  10.1021/acs.jmedchem.3c00818

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。
• Über Derivate des Iminodibenzyls
  作者：W. Schindler、F. Häfliger

  DOI：10.1002/hlca.19540370211

  日期：——

  1. Es wird die Darstellung von aminoalkylierten und aminoacylierten Derivaten des Iminodibenzyls (10, 11-Dihydro-5-dibenzo-[b, f]-azepin) beschrieben.

  1.描述了亚氨基二苄基（10，11-二氢-5-二苯并-[b，f]-氮杂）的氨基烷基化和氨基酰化衍生物的制备。
• TRICYCLIC COMPOUNDS AS ANTICANCER AGENTS
  申请人：Ohlmeyer Michael

  公开号：US20140213578A1

  公开（公告）日：2014-07-31

  Tricyclic chemical modulators of FOXO transcription factor proteins are disclosed. The compounds are useful to treat cancer, age-onset proteotoxicity, stress-induced depression, inflammation, and acne. The compounds are of the following phenothiazine, dibenzoazepine and annulene and similar genera:

  本文披露了三环化学调节剂对FOXO转录因子蛋白的调节作用。这些化合物可用于治疗癌症、年龄相关蛋白质毒性、压力引起的抑郁症、炎症和痤疮。这些化合物属于以下苯硫噻嗪、二苯并氮杂环和环戊烯类似物系列：
• Hulinska, Hana; Polivka, Zdenek; Jilek, Jiri, Collection of Czechoslovak Chemical Communications, 1988, vol. 53, # 8, p. 1820 - 1844
  作者：Hulinska, Hana、Polivka, Zdenek、Jilek, Jiri、Sindelar, Karel、Holubek, Jiri、et al.

  DOI：——

  日期：——
• Inhibitory effect of phenothiazine- and phenoxazine-derived chloroacetamides on Leishmania major growth and Trypanosoma brucei trypanothione reductase
  作者：Ana Marcu、Uta Schurigt、Klaus Müller、Heidrun Moll、R. Luise Krauth-Siegel、Helge Prinz

  DOI：10.1016/j.ejmech.2015.11.023

  日期：2016.1

  A number of phenothiazine-, phenoxazine- and related tricyclics-derived chloroacetamides were synthesized and evaluated in vitro for antiprotozoal activities against Leishmania major (L. major) promastigotes. Several analogs were remarkably potent inhibitors, with antileishmanial activities being comparable or superior to those of the reference antiprotozoal drugs. Furthermore, we explored the structure activity relationships of N-10 haloacetamides that influence the potency of such analogs toward inhibition of L major promastigote growth in vitro. With respect to the mechanism of action, selected compounds were evaluated for time -dependent inactivation of Trypanosoma brucei trypanothione reductase. Our results are indicative of a covalent interaction which could account for potent antiprotozoal activities. (C) 2015 Elsevier Masson SAS. All rights reserved.