2-(6-Hydroxy-2,3,4,9-tetrahydro-1H-carbazol-3-yl)-isoindole-1,3-dione | 171783-42-9

• 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: 2-(6-Hydroxy-2,3,4,9-tetrahydro-1H-carbazol-3-yl)-isoindole-1,3-dione
• 英文别名: 2-(6-hydroxy-2,3,4,9-tetrahydro-1H-carbazol-3-yl)isoindole-1,3-dione
• CAS: 171783-42-9
• 化学式: C₂₀H₁₆N₂O₃
• 分子量: 332.359
• InChiKey: JIHUMVXVXIIPKK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  25
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  73.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(6-Hydroxy-2,3,4,9-tetrahydro-1H-carbazol-3-yl)-isoindole-1,3-dione 在 一水合肼 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 27.0h， 生成 (6-amino-6,7,8,9-tetrahydro-5H-carbazol-3-yl) trifluoromethanesulfonate
  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 、 三溴化硼 、 potassium carbonate 、 溶剂黄146 、 pyridinium chlorochromate 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 反应 7.5h， 生成 2-(6-Hydroxy-2,3,4,9-tetrahydro-1H-carbazol-3-yl)-isoindole-1,3-dione
  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

• 5-(Sulfonyl)oxy-tryptamines and ethylamino side chain restricted derivatives. Structure–affinity relationships for h5-HT 1B and h5-HT 1D receptors
  作者：Tjeerd Barf、Håkan Wikström、Petrus J. Pauwels、Christiane Palmier、Stephanie Tardif、Max Lundmark、Staffan Sundell

  DOI：10.1016/s0968-0896(98)00079-0

  日期：1998.9

  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.
• Binding of <i>O</i>-Alkyl Derivatives of Serotonin at Human 5-HT1Dβ Receptors
  作者：Richard A. Glennon、Seoung-Soo Hong、Mikhail Bondarev、Ho Law、Malgorzata Dukat、Suman Rakhit、Patricia Power、Ermei Fan、Diana Kinneau、Rajender Kamboj、Milt Teitler、Katharine Herrick-Davis、Carol Smith

  DOI：10.1021/jm950498t

  日期：1996.1.1

  populations of receptors. Examination of a series of 5-(alkyloxy)tryptamine derivatives demonstrated that compounds with unbranched alkyl groups of up to eight carbon atoms bind with high affinity at human 5-HT1D beta receptors (Ki < 5 nM) but demonstrate less than 50-fold selectivity relative to 5-HT1A receptors. Alkyl groups longer than eight carbon atoms impart reduced affinity for 5-HT1A receptors whereas

  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