11H-dibenzo[b,e]azepine 5-oxide | 74860-03-0

• 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: 11H-dibenzo[b,e]azepine 5-oxide
• 英文别名: 11H-dibenz[b,e]azepine-5-oxide；11H-dibenzo[b,e]azepine5-oxide；morphanthridine 5-oxide；morphanthridine-5-oxide；11H-dibenz[b,e]azepine,5-oxide；5-oxido-11H-benzo[c][1]benzazepin-5-ium
• CAS: 74860-03-0
• 化学式: C₁₄H₁₁NO
• 分子量: 209.247
• InChiKey: ZCVGKKXCUXOPMT-UHFFFAOYSA-N

物化性质

• 熔点：
  125.0-126.5 °C(Solv: ethyl acetate (141-78-6))
• 沸点：
  394.1±45.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  28.8
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  11H-dibenzo[b,e]azepine 5-oxide 在 palladium on activated charcoal lithium aluminium tetrahydride 、 aluminium amalgam 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 氯仿 、 水 为溶剂， 20.0 ℃ 、275.8 kPa 条件下， 反应 21.17h， 生成 {2-hydroxy-2,3,9,13b-tetrahydro-1H-dibenzo[c,f]pyrrolo[2,1-a]azepin-1-yl}methylethanesulfonate
  参考文献：
  名称：

  Asymmetric 1,3-dipolar reactions of 3-sulfinylfuran-2(5 H )-ones with 11 H -dibenzo[ b,e ]azepine 5-oxide. Synthesis of pyrroloazepines via isoxazoloazepines

  摘要：

  The addition of morphanthridine N-oxide (1) to homochiral 3-p-tolylsulfinylfuran-2(5H)-ones (2a and 2b) under mild conditions affords furoisoxazoloazepines (3a and 3b) in high yields and with complete regioselectivity. The pi-facial and endo-selectivities are also complete from 2a, which yields anti-3a-endo as the only diastereoisomer, whereas cycloreversion determines that the anti-3b-endo adduct can be almost exclusively isolated from 2b. Proper manipulation of the furoisoxazoloazepines allows the synthesis of the optically pure isoxazoloazepines and pyrroloazepines. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2004.04.108
• 作为产物：
  描述：

  [2-(苄)苯基]甲醇 在 硫酸 、 2-(Phenylsulfonyl)-3-phenyloxaziridin 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 11H-dibenzo[b,e]azepine 5-oxide
  参考文献：
  名称：

  Synthesis and structure–activity relationship of 2-(aminoalkyl)-2,3,3a,8-tetrahydrodibenzo[c,f]isoxazolo[2,3-a]azepine derivatives: a novel series of 5-HT2A/2C receptor antagonists. Part 1

  摘要：

  The synthesis of a series of novel 2-(aminoalkyl)-2,3,3a,8-tetrahydrodibenzo[c,f]isoxazolo[2,3-a]azepine derivatives as well as their 5-HT2A/2C and H-1 receptor binding affinities are described. The in vivo activity as potential anxiolytics of the svnthesised compounds was measured in a mCPP challenge test. One of the compounds, 2a, proved to be a potent 5-HT2A 2C c receptor antagonist showing as well oral activity and therefore could be considered as a potential anxiolytic/antidepressant agent. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00721-1

文献信息

• Tetracyclic heterocycles as CNS agents
  作者：Robert Bruce Moffett

  DOI：10.1002/jhet.5570170226

  日期：1980.3

  A considerable number of new tri and tetracyclic heterocycles (II) and open chain intermediates were synthesized. These were tested in a battery of assays designed to reveal central nervous system (CNS) activity. However, none showed useful activity greater than known analogs.

  合成了大量新的三环和四环杂环（II）和开链中间体。在一系列旨在揭示中枢神经系统（CNS）活性的检测方法中对它们进行了测试。然而，没有一个显示出比已知类似物更大的有用活性。
• Search for ideal sulfinyl dienophile and dipolarophile
  作者：José L. García Ruano、Ana M. Martín Castro、Jesús H. Rodríguez Ramos

  DOI：10.1002/hc.10066

  日期：——

  substituted vinyl sulfoxides so far reported, (Z)-3-p-tolylsulfinyl acrylonitriles are proposed as the best sulfinyl dienophiles. The stereoselective synthesis of these compounds was optimized by hydrocyanation of sulfinyl alkynes with Et2AlCN. Their behavior as chiral dienophiles and dipolarophiles is responsible for the high stereocontrol of Diels–Alder and 1,3-dipolar reactions, respectively. © 2002 Wiley

  通过分析迄今为止报道的不同取代乙烯基亚砜的优缺点，(Z)-3-p-甲苯基亚磺酰基丙烯腈被认为是最好的亚磺酰基亲二烯体。这些化合物的立体选择性合成通过亚磺酰基炔烃与 Et2AlCN 的氢氰化作用进行了优化。它们作为手性亲二烯体和偶极体的行为分别导致 Diels-Alder 和 1,3-偶极反应的高度立体控制。© 2002 Wiley Periodicals, Inc. 杂原子化学 13:453–462, 2002; 在线发表于 Wiley Interscience (www.interscience.wiley.com)。DOI 10.1002/hc.10066
• Substituted tetracyclic azepine derivatives
  申请人：Janssen Pharmaceutica N.V.

  公开号：US05552399A1

  公开（公告）日：1996-09-03

  This invention concerns the compounds of formula (I), the pharmaceutically acceptable salts and stereoisomeric forms thereof, and also the N-oxide forms thereof. ##STR1## wherein: R.sup.1 and R.sup.2 each independently are hydrogen; C.sub.1-6 alkyl; C.sub.1-6 alkylcarbonyl; trihalomethylcarbonyl; C.sub.1-6 alkyl substituted with hydroxy, C.sub.1-6 alkyloxy, carboxyl, C.sub.1-6 alkylcarbonyloxy, C.sub.1-6 alkyloxycarbonyl or aryl; or R.sup.1 and R.sup.2 taken together with the nitrogen atom to which they are attached may form a morpholinyl ring or an optionally substituted heterocycle; R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.9, R.sup.10, R.sup.11 or R.sup.12 each independently are hydrogen, halo, cyano, hydroxy, trifluoromethyl, trifluoromethoxy, carboxyl, nitro, amino, mono- or di(C.sub.1-6 alkyl)-amino, C.sub.1-6 alkylcarbonylamino, aminosulfonyl, mono- or di(C.sub.1-6 alkyl)-aminosulfonyl, C.sub.1-6 alkyl, C.sub.1-6 alkyloxy, C.sub.1-6 alkylcarbonyl, C.sub.1-6 alkyloxy-carbonyl; R.sup.7 and R.sup.8 are each independently hydrogen, hydroxy, C.sub.1-6 alkyl, C.sub.1-6 alkyloxy or R.sup.7 and R.sup.8 taken together may form mono- or di(cyano)methylene, or together with the carbon atom to which they are attached form a carbonyl or a spiro substituent; or R.sup.7 and R.sup.8 taken together may form methylene; R.sup.13 is hydrogen, C.sub.1-6 alkyl, or trifluoromethyl; R.sup.14 is hydrogen, C.sub.1-6 alkyl, cyano, or trifluoromethyl; n is zero to 6. These compounds were tested as mCPP-antagonists in rats. The compounds of formula (I) may be used as therapeutic agents in the treatment or the prevention of CNS disorders, cardiovascular disorders or gastrointestinal disorders.

  这项发明涉及式(I)的化合物，其药学上可接受的盐和立体异构体，以及它们的N-氧化物形式。其中：R.sup.1和R.sup.2分别独立地是氢；C.sub.1-6烷基；C.sub.1-6烷基羰基；三卤甲基羰基；带有羟基、C.sub.1-6烷氧基、羧基、C.sub.1-6烷基羰氧基、C.sub.1-6烷氧羰基或芳基的C.sub.1-6烷基；或者R.sup.1和R.sup.2与它们所连接的氮原子一起可以形成吗啡啉环或一个可选择地取代的杂环；R.sup.3、R.sup.4、R.sup.5、R.sup.6、R.sup.9、R.sup.10、R.sup.11或R.sup.12分别独立地是氢、卤、氰、羟基、三氟甲基、三氟甲氧基、羧基、硝基、氨基、单或双(C.sub.1-6烷基)-氨基、C.sub.1-6烷基羰胺基、氨基磺酰基、单或双(C.sub.1-6烷基)-氨基磺酰基、C.sub.1-6烷基、C.sub.1-6烷氧基、C.sub.1-6烷基羰基、C.sub.1-6烷氧羰基；R.sup.7和R.sup.8各自独立地是氢、羟基、C.sub.1-6烷基、C.sub.1-6烷氧基或R.sup.7和R.sup.8一起可以形成单或双(氰)亚甲基，或者与它们连接的碳原子一起形成羰基或螺旋取代基；或者R.sup.7和R.sup.8一起可以形成亚甲基；R.sup.13是氢、C.sub.1-6烷基或三氟甲基；R.sup.14是氢、C.sub.1-6烷基、氰或三氟甲基；n为0到6。这些化合物在大鼠中作为mCPP拮抗剂进行了测试。式(I)的化合物可用作治疗或预防中枢神经系统疾病、心血管疾病或消化系统疾病的治疗剂。
• [EN] SUBSTITUTED TETRACYCLIC AZEPINE DERIVATIVES WHICH HAVE AFFINITY FOR 5-HT2 RECEPTORS<br/>[FR] DERIVES D'AZEPINE TETRACYCLIQUE SUBSTITUES, PRESENTANT UNE AFFINITE POUR LES RECEPTEURS 5-HT2
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：WO1996014320A1

  公开（公告）日：1996-05-17

  (EN) This invention concerns the compounds of formula (I), the pharmaceutically acceptable salts and stereoisomeric forms thereof, and also the $i(N)-oxide forms thereof. In formula (I) R1 and R2 each independently are hydrogen; C1-6alkyl; C1-6alkylcarbonyl; trihalomethylcarbonyl; C1-6alkyl substituted with hydroxy, C1-6alkyloxy, carboxyl, C1-6alkylcarbonyloxy, C1-6alkyloxycarbonyl or aryl; or R1 and R2 taken together with the nitrogen atom to which they are attached may form a morpholinyl ring or an optionally substitued heterocycle; R3, R4, R5, R6, R9, R10, R11 or R12 each independently are hydrogen, halo, cyano, hydroxy, trifluoromethyl, trifluoromethoxy, carboxyl, nitro, amino, mono- or di(C1-6alkyl)-amino, C1-6alkylcarbonylamino, aminosulfonyl, mono- or di(C1-6alkyl)-aminosulfonyl, C1-6alkyl, C1-6alkyloxy, C1-6alkylcarbonyl, C1-6alkyloxy-carbonyl; R7 and R8 are each independently hydrogen, hydroxy, C1-6alkyl, C1-6alkyloxy or R7 and R8 taken together may form mono- or di(cyano)methylene, or together with the carbon atom to which they are attached form a carbonyl or a spiro substituent; or R7 and R8 taken together may form methylene; R13 is hydrogen, C1-6alkyl, or trifluoromethyl; R14 is hydrogen, C1-6alkyl, cyano, or trifluoromethyl; n is zero to 6. These compounds were tested as mCPP-antagonists in rats. The compounds of formula (I) may be used as therapeutic agents in the treatment or the prevention of CNS disorders, cardiovascular disorders or gastrointestinal disorders.(FR) La présente invention concerne les composés représentés par la formule générale (I), leurs sels acceptables du point de vue pharmaceutique, leurs formes stéréo-isomères, ainsi que leurs formes $i(N)-oxyde. Dans cette formule R1 et R2 sont chacun indépendamment hydrogène, C1-6alkyle, C1-6alkylocarbonyle, trihalométhylocarbonyle, C1-6alkyle substitué par un hydroxy, par un C1-6alkylocarbonyloxy, par un C1-6alkylocarbonyle, ou par un aryle; ou bien, R1 et R2 pris ensemble avec l'atome d'azote auquel ils sont attachés peuvent former un noyau morpholinyle ou un hétérocycle éventuellement substitué; R3, R4, R5, R6, R9, R10, R11 ou R12 sont chacun indépendamment hydrogène, halo, cyano, hydroxy, trifluorométhyle, trifluorométhoxy, carboxyle, nitro, amino, mono- ou di(C1-6alkyl)-amino, C1-6alkylocarbonylamino, aminosulfonyle, mono- ou di(C1-6alkyl)-aminosulfonyle, C1-6alkyloxy-carbonyle; R7 et R8 sont chacun indépendamment hydrogène, hydroxy, C1-6alkyle, C1-6alkyloxy, ou bien R7 et R8 pris ensemble peuvent former un mono- ou di(cyano)méthylène, ou former, avec l'atome de carbone auquel ils sont attachés, un substitut carbonyle ou spiro; en outre, R7 et R8 pris ensemble peuvent former un méthylène; R13 est hydrogène, C1-6alkyle ou trifluorométhyle; R14 est hydrogène, C1-6alkyle, cyano ou trifluorométhyle; n est un entier valant de zéro à 6. Ces composés ont été testés chez le rat comme antagonistes CPPm. Ces composés de la formule (I) sont utilisables comme agents thérapeutiques dans le traitement ou la prévention des troubles du système nerveux central, des troubles cardio-vasculaires ou des troubles gastro-intestinaux.

  本发明涉及式（I）的化合物，其在药学上可接受的盐和立体异构体形式，以及其$i(N)-氧化物形式。在式（I）中，R1和R2各自独立地为氢; C1-6烷基; C1-6烷基羰基; 三卤甲基羰基; C1-6烷基取代羟基，C1-6烷氧基，羧基，C1-6烷基羰氧基，C1-6烷氧羰基或芳基; 或R1和R2与它们连接的氮原子一起可以形成吗啡啶环或可选择取代的杂环; R3、R4、R5、R6、R9、R10、R11或R12各自独立地为氢、卤、氰、羟基、三氟甲基、三氟甲氧基、羧基、硝基、氨基、单或双（C1-6烷基）-氨基，C1-6烷基羰基胺基，氨基磺酰基，单或双（C1-6烷基）-氨基磺酰基，C1-6烷基，C1-6烷氧基，C1-6烷基羰基，C1-6烷氧羰基; R7和R8各自独立地为氢，羟基，C1-6烷基，C1-6烷氧基或R7和R8一起可以形成单或双（氰）亚甲基，或与它们连接的碳原子一起形成羰基或螺旋取代基; 或R7和R8一起可以形成亚甲基; R13为氢，C1-6烷基或三氟甲基; R14为氢，C1-6烷基，氰或三氟甲基; n为0到6。这些化合物在大鼠中作为mCPP拮抗剂进行了测试。式（I）的化合物可用作治疗或预防中枢神经系统疾病、心血管疾病或胃肠道疾病的治疗剂。
• Regio- and stereoselective synthesis of pyrrolo or azepine-fused cyclopenta[<i>d</i>]isoxazolines from 2-<i>p</i>-tolylsulfinylcyclopent-2-en-1-one
  作者：José L. García Ruano、José F. Soriano、Alberto Fraile、M. Rosario Martín、Alberto Núñez

  DOI：10.1080/17415993.2012.705286

  日期：2013.4.1

  Reactions of enantiopure 2-p-tolylsulfinylcyclopent-2-en-1-one with cyclic nitrones afforded pyrrolo or azepine-fused cyclopenta[d]isoxazolidines in high yields under mild conditions. Comparison of these results with those obtained with cyclopent-2-en-1-one as the dipolarophile shows that the sulfinyl group increases the reactivity of the enonic system and efficiently controls the pi-facial and endo/exo selectivities of the cycloadditions, which are also dependent on the easy cycloreversion of the resulting compounds. Results obtained in reactions with other dipoles (benzonitrile oxides and those resulting from allenoate and PPh3) are also reported.[GRAPHICS].