5-(3-氯-丙基)-10,11-二氢-5H-二苯并[b,f]氮杂卓 | 16036-79-6

• 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: 5-(3-氯-丙基)-10,11-二氢-5H-二苯并[b,f]氮杂卓
• 英文名称: 5-(3-chloropropyl)-10,11-dihydro-5H-dibenzo[b,f]azepine
• 英文别名: 5-(3-Chlorpropyl)-10,11-dihydro-5H-dibenzoazepin；11-(3-chloropropyl)-5,6-dihydrobenzo[b][1]benzazepine
• CAS: 16036-79-6
• 化学式: C₁₇H₁₈ClN
• 分子量: 271.79
• InChiKey: BXMXGIZWHZIJPA-UHFFFAOYSA-N

物化性质

• 熔点：
  43-45°C
• 沸点：
  401.5±44.0 °C(Predicted)
• 密度：
  1.130±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿、二氯甲烷、DMSO、乙酸乙酯

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  3.2
• 氢给体数：
  0
• 氢受体数：
  1

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  5-(3-氯-丙基)-10,11-二氢-5H-二苯并[b,f]氮杂卓 在 sodium azide 作用下， 以 二甲基亚砜 、 苯 为溶剂， 反应 48.0h， 以61%的产率得到5-(3-azidopropyl)-10,11-dihydro-5H-dibenzo[b,f]azepine
  参考文献：
  名称：

  In vitro antiplasmodial activity of triazole-linked chloroquinoline derivatives synthesized from 7-chloro-N-(prop-2-yn-1-yl)quinolin-4-amine

  摘要：

  The synthesis and in vitro evaluation of novel triazole-linked chloroquinoline derivatives as potential antiplasmodial agents against Plasmodium falciparum is reported. The 15 synthesized target compounds were obtained by means of a copper(I)-mediated click reaction between a variety of 1,2- and 1,3-azidoamines and 7-chloro-N-(prop-2-yn-1-yl) quinolin-4-amine in moderate to good yields (53-85%). The compounds were screened for antiplasmodial activity against NF54 chloroquine-sensitive and Dd2 chloroquine-resistant strains, alongside chloroquine and artesunate as reference compounds. Six of the test compounds revealed a 3-5 fold increase in antiplasmodial activity against chloroquine-resistant strain Dd2 compared to chloroquine. Among the six compounds with good antiplasmodial activity, a reduced cross-resistance relative to artesunate (>3 fold in comparison to chloroquine) was observed, mainly in derivatives that incorporated chloroquine-resistance reversing pharmacophores. A general trend for reduced chloroquine cross-resistance was also detected among 12 out of the 15 compounds tested. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.06.044
• 作为产物：
  描述：

  亚氨基二苄 在 三氟化硼四氢呋喃络合物 作用下， 生成 5-(3-氯-丙基)-10,11-二氢-5H-二苯并[b,f]氮杂卓
  参考文献：
  名称：

  Influence of chain length and N-alkylation on the selective serotonin receptor ligand 9-(aminomethyl)-9,10-dihydroanthracene

  摘要：

  Comparison of the serotonin 5-HT2A receptor affinities of chain lengthened and N-alkylated analogues of the novel ligand 9-aminomethyl-9,10-dihydroanthracene (AMDA) and a structurally similar prototypical tricyclic amine imipramine suggests that the two agents bind to the receptor in different fashions. The demonstration that AMDA is highly selective for serotonin receptors (5-HT2A, K-i = 20 nM; 5-HT2c, K-i = 43 nM) versus the dopamine D-2 receptor (K-i >10,000 nM), as well as the serotonin and norepinephrine transporters (Ki >10,000 nM) further suggests that AMDA and the nonselective ligand imipramine interact with these target macromolecules in different ways. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00023-3
• 作为试剂：
  描述：

  亚氨基二苄 、 正丁基锂 、 1-溴-3-氯丙烷 、 甲苯 在 5-(3-氯-丙基)-10,11-二氢-5H-二苯并[b,f]氮杂卓 作用下， 以 乙醚 、 正己烷 为溶剂， 反应 29.0h， 以there was obtained 7.0 gms的产率得到5-(3-氯-丙基)-10,11-二氢-5H-二苯并[b,f]氮杂卓
  参考文献：
  名称：

  5-(3-)SUBSTITUTED-10,11-DIHYDRO-5H-dibenz[b,f]azepines

  摘要：

  本发明揭示了作为抗抑郁剂使用的5-(3-)取代的10,11-二氢-5H-二苯[b,f]氮杂环化合物及其制备方法。

  公开号：

  US03968217A1

文献信息

• Reversed isoniazids: Design, synthesis and evaluation against Mycobacterium tuberculosis
  作者：Malkeet Kumar、Kawaljit Singh、Andile H. Ngwane、Fahreta Hamzabegovic、Getahun Abate、Bienyameen Baker、Ian Wiid、Daniel F. Hoft、Peter Ruminski、Kelly Chibale

  DOI：10.1016/j.bmc.2017.12.047

  日期：2018.2

  Novel reversed isoniazid (RINH) agents were synthesized by covalently linking isoniazid with various efflux pump inhibitor (EPI) cores and their structural motifs. These RINH agents were then evaluated for anti-mycobacterial activity against sensitive, isoniazid mono-resistant and MDR clinical isolates of M. tuberculosis and a selected number of compounds were also tested ex vivo for intracellular

  通过将异烟肼与各种外排泵抑制剂（EPI）核及其结构基序共价连接，合成了新型反向异烟肼（RINH）剂。这些RINH剂然后针对敏感，异烟肼单抗性和MDR临床分离株的抗分枝杆菌活性的评估结核分枝杆菌和所选择的一些化合物还测试了离体细胞内的活性以及在溴化乙锭（EB）测定外排泵抑制功效。针对的各种菌株一些化合物的效力的结核分枝杆菌（4A - ç，7和8 ;分枝杆菌H37Rv-MIC 99 ≤1.25μM，R5401-MIC 99≤2.5微米，X_61-MIC 99 ≤5微米）证明的逆转抗结核剂战略走向新的抗分枝杆菌剂的发展，解决耐药性的迅速增长的问题的可能性。此外，对于> 90％的通过抑制巨噬细胞活性1A - Ç和图3b（MIC 90 ≤13.42μM）和EB的抑制流出证明这些化合物是令人鼓舞的。
• Sequential Metabolism of Secondary Alkyl Amines to Metabolic-Intermediate Complexes: Opposing Roles for the Secondary Hydroxylamine and Primary Amine Metabolites of Desipramine, (<i>S</i>)-Fluoxetine, and <i>N-</i>Desmethyldiltiazem
  作者：Kelsey L. Hanson、Brooke M. VandenBrink、Kantipudi N. Babu、Kyle E. Allen、Wendel L. Nelson、Kent L. Kunze

  DOI：10.1124/dmd.110.032391

  日期：2010.6

  Three secondary amines desipramine (DES), ( S )-fluoxetine [( S )-FLX], and N -desmethyldiltiazem (MA) undergo N -hydroxylation to the corresponding secondary hydroxylamines [ N -hydroxydesipramine, ( S )- N -hydroxyfluoxetine, and N -hydroxy- N -desmethyldiltiazem] by cytochromes P450 2C11, 2C19, and 3A4, respectively. The expected primary amine products, N -desmethyldesipramine, ( S )-norfluoxetine, and N,N -didesmethyldiltiazem, are also observed. The formation of metabolic-intermediate (MI) complexes from these substrates and metabolites was examined. In each example, the initial rates of MI complex accumulation followed the order secondary hydroxylamine > secondary amine ≫ primary amine, suggesting that the primary amine metabolites do not contribute to formation of MI complexes from these secondary amines. Furthermore, the primary amine metabolites, which accumulate in incubations of the secondary amines, inhibit MI complex formation. Mass balance studies provided estimates of the product ratios of N -dealkylation to N -hydroxylation. The ratios were 2.9 (DES-CYP2C11), 3.6 [( S )-FLX-CYP2C19], and 0.8 (MA-CYP3A4), indicating that secondary hydroxylamines are significant metabolites of the P450-mediated metabolism of secondary alkyl amines. Parallel studies with N -methyl-d3-desipramine and CYP2C11 demonstrated significant isotopically sensitive switching from N -demethylation to N -hydroxylation. These findings demonstrate that the major pathway to MI complex formation from these secondary amines arises from N -hydroxylation rather than N -dealkylation and that the primary amines are significant competitive inhibitors of MI complex formation.

  三种仲胺去甲丙咪嗪（DES）、（S）-氟西汀[（S）-FLX]和N-去甲基地尔硫卓（MA）分别经细胞色素P450 2C11、2C19和3A4催化进行N-羟基化反应，生成相应的仲羟基胺[N-羟基去甲丙咪嗪、（S）-N-羟基氟西汀和N-羟基-N-去甲基地尔硫卓]。同时，也观察到了预期的伯胺产物：N-去甲基去甲丙咪嗪、（S）-去甲氟西汀和N,N-二去甲基地尔硫卓。研究了这些底物和代谢物形成代谢中间体（MI）复合物的过程。在每种情况下，MI复合物积累的初始速率遵循仲羟基胺 > 仲胺 ≫ 伯胺的顺序，表明伯胺代谢物不参与这些仲胺形成MI复合物的过程。此外，在仲胺孵育中积累的伯胺代谢物抑制MI复合物的形成。质量平衡研究表明，N-脱烷基化与N-羟基化的产物比例估计为2.9（DES-CYP2C11）、3.6[（S）-FLX-CYP2C19]和0.8（MA-CYP3A4），表明仲羟基胺是P450介导的仲烷基胺代谢的重要代谢物。与N-甲基-d3-去甲丙咪嗪和CYP2C11的平行研究表明，存在从N-脱甲基化到N-羟基化的显著同位素敏感性转换。这些发现表明，这些仲胺形成MI复合物的主要途径来自N-羟基化而非N-脱烷基化，并且伯胺是MI复合物形成的显著竞争性抑制剂。
• N-substituted azaheterocyclic carboxylic acids and esters thereof
  申请人：Novo Nordisk A/S

  公开号：US06239148B1

  公开（公告）日：2001-05-29

  The present invention relates to novel N-substituted azaheterocyclic carboxylic acids and esters thereof in which a substituted alkyl chain forms part of the N-substituent or salts thereof, to methods for their preparation, to compositions containing them, and to their use for the clinical treatment of painful, hyperalgesic and/or inflammatory conditions in which C-fibers play a pathophysiological role by eliciting neurogenic pain or inflammation.

  本发明涉及新型N-取代的氮杂环羧酸及其酯，其中取代烷基链构成N-取代基的一部分或其盐，以及其制备方法、含有它们的组合物，以及它们在临床治疗疼痛、高敏感和/或炎症条件中的应用，其中C-纤维通过引发神经源性疼痛或炎症发挥病理生理作用。
• 1,4-disubstituted piperazines
  申请人：Novo Nordisk A/S

  公开号：US05916889A1

  公开（公告）日：1999-06-29

  The present invention relates to 1,4-disubstituted piperazines of the general formula ##STR1## wherein X, Y, Z, R.sup.1, R.sup.2 and r are as defined in the detailed part of the present description or salts thereof, to methods for their preparation, to compositions containing them, and to their use for the clinical treatment of painful, hyperalgesic and/or inflammatory conditions in which C-fibers play a pathophysiological role by eliciting neurogenic pain or inflammation as well as their use for the treatment of indications caused by or related to the secretion and circulation of insulin antagonizing peptides, e.g. non-insulin-dependent diabetes mellitus (NIDDM) and ageing-associated obesity.

  本发明涉及一般式为##STR1##的1,4-二取代哌嗪，其中X、Y、Z、R.sup.1、R.sup.2和r如本说明书详细部分所定义，或其盐，以及它们的制备方法、含有它们的组合物，以及它们用于临床治疗疼痛、高敏感和/或炎症症状的用途，其中C-纤维通过诱导神经源性疼痛或炎症发挥病理生理作用，以及它们用于治疗由胰岛素拮抗肽的分泌和循环引起或相关的适应症，例如非胰岛素依赖性糖尿病（NIDDM）和与衰老相关的肥胖症。
• Studies on psychotropic agents. I. Synthesis of 3,8-disubstituted-1-oxa-3,8-diazaspiro(4,5)decan-2,4-dione derivatives.
  作者：YASUTAKA NAGAI、AKIO MAKI、HISASHI KANDA、KAGAYAKI NATSUKA、SUSUMU UMEMOTO

  DOI：10.1248/cpb.24.1179

  日期：——

  A series of 3, 8-disubstituted-1-oxa-3, 8-diazaspiro [4, 5] decan-2, 4-diones (XI) were synthesized for pharmacological testing. 3-Substituted-8-benzyl compounds (IIIb-h), the intermediates of XI, were prepared by the following three methods : 1) condensation of methyl 1-benzyl-4-hydroxyisonipecotate (II) with urea, followed by alkylation, 2) treatment of II with isocyanates and 3) reaction of 1-benzyl-4-cyano-4-piperidinol (I) with isocyanates followed by hydrolysis. The last method was inferior to the other two methods. Reductive debenzylation of III followed by condensation with appropriate halides afforded XI. Among the compounds (XI) synthesized, 8-[3-(2-chlorophenothiazin-10-yl) propyl]-3-methyl compound (XIa) had excellent central nervous system depressing activities.

  为了进行药理测试，合成了一系列3,8-二取代-1-氧杂-3,8-二氮杂螺[4,5]癸烷-2,4-二酮(XI)。3-取代-8-苄基化合物(IIIb-h)是XI的中间体，通过以下三种方法制备： 1) 甲基1-苄基-4-羟基异哌啶酸酯(II)与尿素缩合，随后进行烷基化 2) 将II与异氰酸酯反应 3) 1-苄基-4-氰基-4-哌啶醇(I)与异氰酸酯反应，然后水解 最后一种方法不如前两种方法。III脱苄基还原后与适当的卤化物缩合得到XI。在合成的化合物(XI)中，8-[3-(2-氯吩噻嗪-10-基)丙基]-3-甲基化合物(XIa)具有优异的中枢神经系统抑制活性。