N-(6-methoxy-1,2,3,4-tetrahydrocarbazol-3-yl)phthalimide | 147009-21-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: N-(6-methoxy-1,2,3,4-tetrahydrocarbazol-3-yl)phthalimide
• 英文别名: 3-phthalimido-6-methoxy-1,2,3,4-tetrahydrocarbazole；2-(6-methoxy-2,3,4,9-tetrahydro-1H-carbazol-3-yl)isoindole-1,3-dione
• CAS: 147009-21-0
• 化学式: C₂₁H₁₈N₂O₃
• 分子量: 346.386
• InChiKey: VIPOQPIKJGSUCR-UHFFFAOYSA-N

物化性质

• 沸点：
  556.8±50.0 °C(Predicted)
• 密度：
  1.391±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  62.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(6-methoxy-1,2,3,4-tetrahydrocarbazol-3-yl)phthalimide 在 一水合肼 作用下， 生成 3-Amino-6-methoxy-1,2,3,4-tetrahydrocarbazole hydrochloride
  参考文献：
  名称：

  5-(Sulfonyl)oxy-tryptamines and ethylamino side chain restricted derivatives. Structure–affinity relationships for h5-HT 1B and h5-HT 1D receptors

  摘要：

  A number of sulfonic acid ester derivatives of serotonin (5-hydroxytryptamine; 5-HT; 1) were prepared and their affinities are compared to that of the reference compound 5-[[(trifluoromethyl)sulfonyl]oxy]-tryptamine (8b). The structure-affinity relationship (SAFIR) is discussed in terms of in vitro binding for cloned human h5-HT1A, h5-HT1B and h5-HT1D receptors. All tryptamine derivatives exhibited the best affinities for h5-HT1D receptors but still, these were comparatively lower than that of compound 8b. 5-Tosylated tryptamine 11b (K-i = 6 nM) and the sulfamate derivatives 13b and 14b (K-i = 7 and 11 nM, respectively) were found to have the highest affinities for the h5-HT1D receptor. Other tryptamine derivatives displayed moderate binding for h5-HT1A and h5-HT1B receptors, along with Ki values ranging from 14-20 nM for the h5-HT1D sites. In addition, the syntheses of two alkylamino side chain restricted derivatives are described. 3-Amino-6-[[(trifluoromethyl)sulfonyl]oxy]-1,2,3,4-tetrahydrocarbazole 21, as well as 4-[5-[[(trifluoromethyl)sulfonyl]oxy]-1H-indol-3-yl]piperidines 24 and 25, induced a shift in selectivity in favor of the h5-HT1B receptor. The relatively longer distance between the basic amine and a hydrogen-bond accepting oxygen in 21, 24 and 25 as compared to the non-restricted tryptamines, is likely responsible for this observation. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)00079-0
• 作为产物：
  描述：

  trans-4-Aminocyclohexanol 在 4 A molecular sieve 、 potassium carbonate 、 溶剂黄146 、 pyridinium chlorochromate 作用下， 以 二氯甲烷 为溶剂， 反应 5.5h， 生成 N-(6-methoxy-1,2,3,4-tetrahydrocarbazol-3-yl)phthalimide
  参考文献：
  名称：

  血清素的O-烷基衍生物在人5-HT1Dβ受体上的结合。

  摘要：

  在人类中，5-HT1D血清素受体代表末端自身受体，并且有一些证据表明5-HT1D配体可用于治疗偏头痛。最广泛使用的5-HT1D激动剂是舒马普坦。然而，据报道该试剂对5-HT1D的选择性相对于5-HT1A受体几乎没有。为了鉴定具有增强的5-HT1D相对于5-HT1A选择性的新型5-羟色胺能药物，我们尝试利用与这两个受体的5-HT结合位点的5-位相关的体积耐受性区域中的可能差异。对一系列5-（烷氧基）色胺的衍生物的研究表明，具有多达8个碳原子的直链烷基的化合物以高亲和力与人5-HT1Dβ受体结合（Ki < 5 nM），但相对于5-HT1A受体，选择性不足50倍。长于八个碳原子的烷基会降低对5-HT1A受体的亲和力，而长于九个碳原子的烷基会导致对5-HT1Dβ受体的亲和力降低的化合物。5-（壬氧基）色胺（10）代表具有最佳5-HT1Dβ亲和力（Ki = 1 nM）和选择性（> 300倍）的化合物。烷基链分支成5-[（（7

  DOI：

  10.1021/jm950498t

文献信息

• Optimization of pharmacokinetic properties by modification of a carbazole-based cannabinoid receptor subtype 2 (CB2) ligand
  作者：Dominik Heimann、Frederik Börgel、Henk de Vries、Kim Bachmann、Victoria E. Rose、Bastian Frehland、Dirk Schepmann、Laura H. Heitman、Bernhard Wünsch

  DOI：10.1016/j.ejmech.2017.10.049

  日期：2018.1

  13b) were synthesized and pharmacologically evaluated. The key step in the synthesis of substituted carbazoles 23a, 24a and 26a was a Fischer indole synthesis. Nucleophilic substitution of tosylated lactate 5 by carbazole anion provided the fluoroisopropyl derivatives 13a and 13b. Partial hydrogenation of the aromatic carbazole system (26a) was not tolerated by the CB2 receptor. A methylsulfonyl moiety

  近来，已经报道了用于中枢神经系统中CB 2受体成像的氟化PET示踪剂[ 18 F] 1a的开发。[ 18 F] 1a与CB 1亚型相比，具有较高的CB 2亲和力和选择性，但在小鼠中具有快速的生物转化。除酰胺水解外，氧化N-脱烷基化和咔唑氧化被认为是主要的代谢途径。基于这些结果，发现具有新的6-取代基（23a，24a），改性的氢化态（26a）和扩大的氟烷基取代基（13a）的新型咔唑衍生物，13b）被合成并进行药理学评价。合成取代咔唑23a，24a和26a的关键步骤是费希尔吲哚合成。咔唑阴离子对甲苯磺酸酯5的亲核取代提供了氟异丙基衍生物13a和13b。CB 2受体不容许芳族咔唑系统（26a）的部分氢化。6位（24a）处的甲磺酰基部分导致CB 2亲和力大大降低，而6甲氧基部分（23a））的耐受性良好。1a的氟乙基侧链中的另一个甲基部分导致氟异丙基衍生物13具有不变的高CB 2亲和力和CB 2：CB
• Use of tetrahydrocarbazone derivatives as 5HT.sub.1 receptor agonists
  申请人：SmithKline Beecham P.L.C.

  公开号：US05464864A1

  公开（公告）日：1995-11-07

  ##STR1## Use of a compound of general formula (I), wherein R.sup.1 represents hydrogen, halogen, trifluoromethyl, nitro, hydroxy, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, arylC.sub.1-6 alkoxy, --CO.sub.2 R.sup.4, --(CH.sub.2).sub.n CN, --(CH.sub.2).sub.n CONR.sup.5 R.sup.6, --(CH.sub.2).sub.n SO.sub.2 NR.sup.5 R.sup.6, C.sub.1-6 alkanoylamino(CH.sub.2).sub.n, or C.sub.1-6 alkylsulphonylamino(CH.sub.2).sub.n ; R.sup.4 represents hydrogen, C.sub.1-6 alkyl or arylC.sub.1-6 alkyl; R.sup.5 and R.sup.6 each independently represent hydrogen or C.sub.1-6 alkyl, or R.sup.5 and R.sup.6 together with the nitrogen atom to which they are attached form a ring; n represents 0, 1 or 2; and R.sup.2 and R.sup.3 each independently represent hydrogen, C.sub.1-6 alkyl; or benzyl or together with the nitrogen atom to which they are attached form a pyrrolidino, piperidino or hexahydroazepino ring; or a physiologically acceptable salt thereof, in the manufacture of a medicament for the treatment of a condition where a 5-HT.sub.1 -like agonist is indicated, for example migraine. Novel compounds of formula (I), processes for preparing them and pharmaceutical compositions containing them are also described.

  在制备治疗5-HT1-样受体激动剂适用的药物时，使用通式（I）的化合物，其中R^1代表氢、卤素、三氟甲基、硝基、羟基、C1-6烷基、C1-6烷氧基、芳基C1-6烷氧基、-CO2R^4、-(CH2)nCN、-(CH2)nCONR^5R^6、-(CH2)nSO2NR^5R^6、C1-6烷酰氨基(CH2)n或C1-6烷基磺酰氨基(CH2)n；R^4代表氢、C1-6烷基或芳基C1-6烷基；R^5和R^6分别独立表示氢或C1-6烷基，或R^5和R^6与其连接的氮原子一起形成环；n代表0、1或2；R^2和R^3分别独立表示氢、C1-6烷基；或苄基，或与其连接的氮原子一起形成吡咯啉、哌啶或六氢脲环；或其生理上可接受的盐，在制备这些化合物和含有它们的药物组合物的过程中也有描述。
• Medicaments 1,2,3,4-tetrahydrocarbazoles and 5-HT.sub.1 agonist use
  申请人：Smithkline Beecham plc

  公开号：US05827871A1

  公开（公告）日：1998-10-27

  Use of a compound of general formula (I): ##STR1## wherein R.sup.1 represents hydrogen, halogen, trifluoromethyl, nitro, hydroxy, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, arylC.sub.1-6 alkoxy, --CO.sub.2 R.sup.4, --(CH.sub.2).sub.n CN, --(CH.sub.2).sub.n CONR.sup.5 R.sup.6, --(CH.sub.2).sub.n SO.sub.2 NR.sup.5 R.sup.6, C.sub.1-6 alkanoylamino(CH.sub.2).sub.n, or C.sub.1-6 alkylsulphonylamino(CH.sub.2).sub.n ; R.sup.4 represents hydrogen, C.sub.1-6 alkyl or arylC.sub.1-6 alkyl; R.sup.5 and R.sup.6 each independently represent hydrogen or C.sub.1-6 alkyl, or R.sup.5 and R.sup.6 together with the nitrogen atom to which they are attached form a ring; n represents 0, 1 or 2; and R.sup.2 and R.sup.3 each independently represent hydrogen, C.sub.1-6 alkyl or benzyl or together with the nitrogen atom to which they are attached form a pyrrolidino, piperidino or hexahydroazepino ring; or a physiologically acceptable salt thereof, in the manufacture of a medicament for the treatment of a condition where a 5-HT.sub.1 -like agonist is indicated, for example migraine. Novel compounds of formula (I), processes for preparing them and pharmaceutical compositions containing them are also described.

  将通用公式(I)的化合物用于制造药物，用于治疗需要5-HT1样受体激动剂的情况，例如偏头痛。公式(I)的新化合物、制备它们的方法以及含有它们的药物组成物也有描述。
• [EN] USE OF TETRAHYDROCARBAZONE DERIVATIVES AS 5HT1 RECEPTOR AGONISTS
  申请人：SMITHKLINE BEECHAM PLC

  公开号：WO1993000086A1

  公开（公告）日：1993-01-07

  (EN) Use of a compound of general formula (I), wherein R1 represents hydrogen, halogen, trifluoromethyl, nitro, hydroxy, C1-6alkyl, C1-6alkoxy, arylC1-6alkoxy, -CO2R4, -(CH2)nCN, -(CH2)nCONR5R6, -(CH2)nSO2NR5R6, C1-6alkanolyamino(CH2)n, or C1-6alkylsulphonylamino(CH2)n; R4 represents hydrogen, C1-6alkyl or arylC1-6alkyl; R5 and R6 each independently represent hydrogen or C1-6¿alkyl, or R5 and R6 together with the nitrogen atom to which they are attached form a ring; n represents 0, 1 or 2; and R2 and R3 each independently represent hydrogen, C¿1-6alkyl or benzyl or together with the nitrogen atom to which they are attached form a pyrrolidino, piperidino or hexahydroazepino ring; or a physiologically acceptable salt thereof, in the manufacture of a medicament for the treatment of a condition where a 5-HT1-like agonist is indicated, for example migraine. Novel compounds of formula (I), processes for preparing them and pharmaceutical compositions containing them are also described.(FR) Utilisation d'un composé de la formule (I) dans laquelle R1 représente hydrogène, halogène, trifluorométhyle, nitro, hydroxy, C1-6alkyle, C1-6alcoxy, arylC1-6alcoxy, -CO2R4, -(CH2)nCN, -(CH2)nCONR5R6, -(CH2)nSO2NR5R6, C1-6alcanoylamino(CH2)n, ou C1-6alkylsulphonylamino(CH2)n; R4 représente hydrogène, C1-6alkyle ou arylC1-6alkyle; R5 et R6 représentent chacun indépendamment hydrogène ou C1-6alkyle, ou R5 et R6 forment avec l'atome d'azote auquel ils sont attachés une chaîne fermée, n représente 0, 1 ou 2; et R2 et R3 représentent chacun indépendamment hydrogène, C1-6alkyle ou benzyle ou forment avec l'atome d'azote auquel ils sont attachés une chaîne fermée pyrrolidino, pipéridino ou hexahydroazépino; ou d'un sel physiologiquement acceptable de ce composé, dans la fabrication d'un médicament destiné au traitement d'états tels que la migraine où un agoniste analogue au 5-HT1 est prescrit. Des composés de la formule (I), leurs procédés de préparation et des compositions pharmaceutiques les contenant sont également décrits.

  使用通式（I）的化合物，其中R1代表氢，卤素，三氟甲基，硝基，羟基，C1-6烷基，C1-6烷氧基，芳基C1-6烷氧基，-CO2R4，-(CH2)nCN，-(CH2)nCONR5R6，-(CH2)nSO2NR5R6，C1-6酰胺基(CH2)n或C1-6烷基磺酰胺基(CH2)n; R4代表氢，C1-6烷基或芳基C1-6烷基; R5和R6各自独立地表示氢或C1-6烷基，或者R5和R6与它们所连接的氮原子一起形成一个环; n表示0，1或2; R2和R3各自独立地表示氢，C1-6烷基或苄基，或者与它们所连接的氮原子一起形成吡咯烷，哌啶或六氢噁唑环; 或其生理上可接受的盐，在制造用于治疗需要5-HT1样受体激动剂的情况的药物中，例如偏头痛。还描述了通式（I）的新化合物、制备它们的方法以及含有它们的制药组合物。
• Medicaments
  申请人：SmithKline Beecham p.l.c.

  公开号：US05637611A1

  公开（公告）日：1997-06-10

  Use of a compound of general formula (I): ##STR1## wherein: R.sup.1 represents hydrogen, halogen, trifluoromethyl, nitro, hydroxy, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, arylC.sub.1-6 alkoxy, --CO.sub.2 R.sup.4, --(CH.sub.2).sub.n CN, --(CH.sub.2).sub.n CONR.sup.5 R.sup.6, --(CH.sub.2).sub.n SO.sub.2 NR.sup.5 R.sup.6, C.sub.1-6 alkanoylamino (CH.sub.2).sub.n, or C.sub.1-6 alkylsulphonylamino (CH.sub.2).sub.n ; R.sup.4 represents hydrogen, C.sub.1-6 alkyl or arylC.sub.1-6 alkyl; R.sup.5 and R.sup.6 each independently represent hydrogen or C.sub.1-6 alkyl, or R.sup.5 and R.sup.6 together with the nitrogen atom to which they are attached form a ring; n represents 0, 1 or 2; and R.sup.2 and R.sup.3 each independently represent hydrogen, C.sub.1-6 alkyl or benzyl or together with the nitrogen atom to which they are attached form a pyrrolidino, piperidino or hexahydroazepino ring; or a physiologically acceptable salt thereof, in the manufacture of a medicament for the treatment of a condition where a 5-HT.sub.1 -like agonist is indicated, for example migraine. Novel compounds of formula (I), processes for preparing them and pharmaceutical compositions containing them are also described.

  使用一般式(I)的化合物：##STR1## 其中：R.sup.1代表氢，卤素，三氟甲基，硝基，羟基，C.sub.1-6烷基，C.sub.1-6烷氧基，芳基C.sub.1-6烷氧基，--CO.sub.2R.sup.4，--(CH.sub.2).sub.n CN，--(CH.sub.2).sub.n CONR.sup.5 R.sup.6，--(CH.sub.2).sub.n SO.sub.2NR.sup.5 R.sup.6，C.sub.1-6烷酰胺基(CH.sub.2).sub.n或C.sub.1-6烷基磺酰胺基(CH.sub.2).sub.n; R.sup.4代表氢，C.sub.1-6烷基或芳基C.sub.1-6烷基; R.sup.5和R.sup.6各自独立地代表氢或C.sub.1-6烷基，或R.sup.5和R.sup.6与它们连接的氮原子一起形成一个环; n代表0、1或2; R.sup.2和R.sup.3各自独立地代表氢、C.sub.1-6烷基或苄基，或者与它们连接的氮原子一起形成吡咯烷，哌啶或六氢噁唑环; 或其生理上可接受的盐，在制造治疗5-HT.sub.1样受体激动剂适用的情况下的药物中，例如偏头痛。还描述了公式(I)的新化合物、制备它们的过程和含有它们的药物组成物。