5-(1-hydroxylcyclohexyl)indole | 262593-62-4

• 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: 5-(1-hydroxylcyclohexyl)indole
• 英文别名: 1-(1H-Indol-5-yl)cyclohexanol；1-(1H-indol-5-yl)cyclohexan-1-ol
• CAS: 262593-62-4
• 化学式: C₁₄H₁₇NO
• 分子量: 215.295
• InChiKey: YWVARHCIOPAINC-UHFFFAOYSA-N

物化性质

• 沸点：
  421.1±20.0 °C(Predicted)
• 密度：
  1.206±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  36
• 氢给体数：
  2
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  5-(1-hydroxylcyclohexyl)indole 在 lithium aluminium tetrahydride 、 三氯化铝 、 sodium methylate 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 乙腈 为溶剂， 反应 35.5h， 生成 1-(2-deoxy-β-D-erythropentafuranosyl)-5-cyclohexylindole
  参考文献：
  名称：

  Hydrophobicity, Shape, and π-Electron Contributions during Translesion DNA Synthesis

  摘要：

  Translesion DNA synthesis, the ability of a DNA polymerase to misinsert a nucleotide opposite a damaged DNA template, represents a common route toward mutagenesis and possibly disease development. To further define the mechanism of this promutagenic process, we synthesized and tested the enzymatic incorporation of two isosteric 5-substituted indolyl-2'deoxyriboside triphosphates opposite an abasic site. The catalytic efficiency for the incorporation of the 5-cyclohexene-indole derivative opposite an abasic site is 75-fold greater than that for the 5-cyclohexyl-indole derivative. The higher efficiency reflects a substantial increase in the k(pol) value (compare 25 versus 0.5 s(-1), respectively) as opposed to an influence on ground-state binding of either non-natural nucleotide. The faster k(pol) value for the 5-cyclohexene-indole derivative indicates that pi-electron density enhances the rate of the enzymatic conformational change step required for insertion opposite the abasic site. However, the kinetic dissociation constants for the non-natural nucleotides are identical and indicate that pi-electron density does not directly influence groundstate binding opposite the DNA lesion. Surprisingly, each non-natural nucleotide can be incorporated opposite natural templating bases, albeit with a greatly reduced catalytic efficiency. In this instance, the lower catalytic efficiency is caused by a substantial decrease in the k(pol) value rather than perturbations in ground-state binding. Collectively, these data indicate that the rate of the conformational change during translesion DNA synthesis depends on T-electron density, while the enhancement in ground-state binding appears related to the size and shape of the non-natural nucleotide.

  DOI：

  10.1021/ja0546830
• 作为产物：
  描述：

  5-溴吲哚 、 环己酮 在 potassium hydride 、 叔丁基锂 作用下， 以 四氢呋喃 为溶剂， 反应 2.75h， 以6 g的产率得到5-(1-hydroxylcyclohexyl)indole
  参考文献：
  名称：

  Hydrophobicity, Shape, and π-Electron Contributions during Translesion DNA Synthesis

  摘要：

  Translesion DNA synthesis, the ability of a DNA polymerase to misinsert a nucleotide opposite a damaged DNA template, represents a common route toward mutagenesis and possibly disease development. To further define the mechanism of this promutagenic process, we synthesized and tested the enzymatic incorporation of two isosteric 5-substituted indolyl-2'deoxyriboside triphosphates opposite an abasic site. The catalytic efficiency for the incorporation of the 5-cyclohexene-indole derivative opposite an abasic site is 75-fold greater than that for the 5-cyclohexyl-indole derivative. The higher efficiency reflects a substantial increase in the k(pol) value (compare 25 versus 0.5 s(-1), respectively) as opposed to an influence on ground-state binding of either non-natural nucleotide. The faster k(pol) value for the 5-cyclohexene-indole derivative indicates that pi-electron density enhances the rate of the enzymatic conformational change step required for insertion opposite the abasic site. However, the kinetic dissociation constants for the non-natural nucleotides are identical and indicate that pi-electron density does not directly influence groundstate binding opposite the DNA lesion. Surprisingly, each non-natural nucleotide can be incorporated opposite natural templating bases, albeit with a greatly reduced catalytic efficiency. In this instance, the lower catalytic efficiency is caused by a substantial decrease in the k(pol) value rather than perturbations in ground-state binding. Collectively, these data indicate that the rate of the conformational change during translesion DNA synthesis depends on T-electron density, while the enhancement in ground-state binding appears related to the size and shape of the non-natural nucleotide.

  DOI：

  10.1021/ja0546830

文献信息

• 3-bicycloindole compounds
  申请人：NPS Allelix Corp.

  公开号：US06562809B1

  公开（公告）日：2003-05-13

  Described herein are compounds selective for a 5-HT1D receptor, which have the general formula:

  本文描述了一些具有选择性5-HT1D受体的化合物，其通式为：
• 3-BICYCLOINDOLE COMPOUNDS AS 5-HT1D RECEPTOR LIGANDS
  申请人：NPS Allelix Corp.

  公开号：EP1114049B1

  公开（公告）日：2003-03-19
• US6562809B1
  申请人：——

  公开号：US6562809B1

  公开（公告）日：2003-05-13
• [EN] 3-BICYCLOINDOLE COMPOUNDS AS 5-HT1D LIGANDS<br/>[FR] COMPOSES DE 3-BICYCLOINDOLE COMME LIGANDS DE 5-HT1D
  申请人：ALLELIX BIOPHARMA

  公开号：WO2000017198A1

  公开（公告）日：2000-03-30

  Described herein are compounds selective for a 5-HT1D receptor, which have general Formula (I) wherein: R1 is selected from the group consisting of a group of Formula (II), H, halo, OH, C¿1-6?alkyl, C1-6alkoxy, C2-6alkenyl, C3-7cycloalkoxy, C3-7cycloalkylthio, optionally substituted furanyl, optionally substituted thienyl, optionally substituted phenyloxy, and others; X is selected from the group consisting of O, S, SO, SO2, NR?10 and CR11R12¿;-----, in ring A and ring B, represents a single or double bond provided that only one double bond is present in a ring at a time; R2 is selected from the group consisting of H, OH, C¿1-6?alkyl and C1-6alkoxy; R?3¿ is selected from the group consisting of H, OH, C¿1-6?alkyl, C1-6alkoxy, C1-6alkylthio and optionally substituted benzyloxy; R?4¿ is selected from the group consisting of H and C¿1-4?alkyl; R?5¿ is selected from the group consisting of H, OH, C¿1-6?alkyl and C1-6alkoxy; R?6¿ is selected from the group consisting of H, OH, C¿1-6?alkoxy or null; R?10¿ is selected from the group consisting of H, C¿1-6?alkyl, and optionally substituted benzyl; one of R?11 and R12¿ is selected from the group consisting of H, C¿1-6?alkyl and optionally substituted benzyl and the other is H; n is selected from the group consisting of an integer of from 1-3; and Z is selected from the group consisting of C and N. Also described is the use of these compounds as pharmaceuticals to treat indications where stimulation of a 5-HT1D receptor is indicated, such as migraine.