ethyl 8-bromo-5-n-octyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate

• 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: ethyl 8-bromo-5-n-octyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate
• 英文别名: 2-carbethoxy-8-bromo-5-n-octyl-1,2,3,4-tetrahydropyrido[4,3-b]indole；2-Carbethoxy-8-bromo-5-n-octyl-1,2,3,4-tetrahydropyrido[4,3-b]indole；ethyl 8-bromo-5-octyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2-carboxylate
• 化学式: C₂₂H₃₁BrN₂O₂
• 分子量: 435.404
• InChiKey: VWDDHINYCZCLAT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  34.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  ethyl 8-bromo-5-n-octyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate 在 水 、 三乙胺 、 potassium hydroxide 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 18.5h， 生成 8-bromo-2-(methylsulfonyl)-5-n-octyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole
  参考文献：
  名称：

  Functionalized tetrahydro-1H-pyrido[4,3-b]indoles: A novel chemotype with Sirtuin 2 inhibitory activity

  摘要：

  Sirtuins are protein deacylases with regulatory roles in metabolism and stress response. Functionalized tetrahydro-1H-pyrido[4,3-b]indoles were identified as preferential sirtuin 2 inhibitors, with in vitro inhibitory potencies in the low micromolar concentrations (IC50 3-4 mu M) for the more promising candidates. The functional relevance of sirtuin inhibition was corroborated in western blots that showed hyperacetylation of p53 and alpha-tubulin in treated HepG2 and MDA-MB-231 cells. Molecular docking showed that the tetrahydropyridoindole scaffold was positioned in the NAD + pocket and the acetylated substrate channel of the sirtuin 2 protein by van der Waals/hydrophobic, H bonding and stacking interactions. Functionalized tetrahydropyridoindoles represent a novel class of sirtuin 2 inhibitors that could be further explored for its therapeutic potential. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.12.027
• 作为产物：
  描述：

  4-溴苯肼盐酸盐 在 sodium hydride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.25h， 生成 ethyl 8-bromo-5-n-octyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate
  参考文献：
  名称：

  Functionalized tetrahydro-1H-pyrido[4,3-b]indoles: A novel chemotype with Sirtuin 2 inhibitory activity

  摘要：

  Sirtuins are protein deacylases with regulatory roles in metabolism and stress response. Functionalized tetrahydro-1H-pyrido[4,3-b]indoles were identified as preferential sirtuin 2 inhibitors, with in vitro inhibitory potencies in the low micromolar concentrations (IC50 3-4 mu M) for the more promising candidates. The functional relevance of sirtuin inhibition was corroborated in western blots that showed hyperacetylation of p53 and alpha-tubulin in treated HepG2 and MDA-MB-231 cells. Molecular docking showed that the tetrahydropyridoindole scaffold was positioned in the NAD + pocket and the acetylated substrate channel of the sirtuin 2 protein by van der Waals/hydrophobic, H bonding and stacking interactions. Functionalized tetrahydropyridoindoles represent a novel class of sirtuin 2 inhibitors that could be further explored for its therapeutic potential. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.12.027

文献信息

• [EN] ICMT Inhibitors<br/>[FR] INHIBITEURS D'ICMT
  申请人：UNIV SINGAPORE

  公开号：WO2013180656A1

  公开（公告）日：2013-12-05

  The invention provides a 1,3,5-substituted indole wherein the substituent at position 1 is a C6 to C12 alkyl group; the substituent at position 3 is CH2NR1R2 wherein R1 is H or C1 to C3 alkyl, R1 being optionally substituted with -OH, -SH, -NH2 or NHalkyl, wherein alkyl is a C1 to C4 alkyl group, and R2 is C1 to C3 alkyl or (CH2)n bonded to position 2 of the indole, wherein n is 1, 2 or 3; and the substituent at position 5 is either an optionally substituted nitrogen containing heteroaromatic ring or an aminosulfonylphenyl group or an alkylsulfonylphenyl group.

  该发明提供了一种1,3,5-取代吲哚，其中位置1处的取代基是C6到C12的烷基基团；位置3处的取代基是CH2NR1R2，其中R1是H或C1到C3的烷基，R1可选择地被-OH，-SH，-NH2或NH烷基取代，其中烷基是C1到C4的烷基基团，R2是C1到C3的烷基或(CH2)n与吲哚的位置2结合，其中n为1、2或3；位置5处的取代基是一个可选择地取代的含氮杂芳环或氨基磺基苯基团或烷基磺基苯基团。
• ICMT INHIBITORS
  申请人：National University of Singapore

  公开号：US20150218095A1

  公开（公告）日：2015-08-06

  The invention provides a 1,3,5-substituted indole wherein the substituent at position 1 is a C6 to C12 alkyl group; the substituent at position 3 is CH 2 NR 1 R 2 wherein R 1 is H or C1 to C3 alkyl, R 1 being optionally substituted with —OH, —SH, —NH 2 or NHalkyl, wherein alkyl is a C1 to C4 alkyl group, and R 2 is C1 to C3 alkyl or (CH 2 ) n bonded to position 2 of the indole, wherein n is 1, 2 or 3; and the substituent at position 5 is either an optionally substituted nitrogen containing heteroaromatic ring or an aminosulfonylphenyl group or an alkylsulfonylphenyl group.

  本发明提供了一种1,3,5-取代吲哚，其中第1位取代基为C6到C12烷基；第3位取代基为CH2NR1R2，其中R1为H或C1到C3烷基，R1可选地被取代为-OH，-SH，-NH2或NH烷基，其中烷基为C1到C4烷基，R2为C1到C3烷基或(CH2)n与吲哚的第2位连接，其中n为1、2或3；第5位取代基为可选取代的含氮杂芳环或氨基磺酰基苯基或烷基磺酰基苯基。
• ICMT inhibitors
  申请人：National University of Singapore

  公开号：US09422238B2

  公开（公告）日：2016-08-23

  The invention provides a 1,3,5-substituted indole wherein the substituent at position 1 is a C6 to C12 alkyl group; the substituent at position 3 is CH2NR1R2 wherein R1 is H or C1 to C3 alkyl, R1 being optionally substituted with —OH, —SH, —NH2 or NHalkyl, wherein alkyl is a C1 to C4 alkyl group, and R2 is C1 to C3 alkyl or (CH2)n bonded to position 2 of the indole, wherein n is 1, 2 or 3; and the substituent at position 5 is either an optionally substituted nitrogen containing heteroaromatic ring or an aminosulfonylphenyl group or an alkylsulfonylphenyl group.

  本发明提供了一种1,3,5-取代吲哚，其中取代基在1号位是一个C6到C12的烷基基团；在3号位是CH2NR1R2，其中R1是H或C1到C3的烷基，R1可以选择性地被取代为-OH，-SH，-NH2或NH烷基，其中烷基是C1到C4的烷基基团，而R2是C1到C3的烷基或(CH2)n与吲哚的2号位连接，其中n为1、2或3；在5号位的取代基是一个可选择性取代的含氮杂环芳香环或氨基磺酰基苯基团或烷基磺酰基苯基团。
• US9422238B2
  申请人：——

  公开号：US9422238B2

  公开（公告）日：2016-08-23
• Functionalized tetrahydro-1H-pyrido[4,3-b]indoles: A novel chemotype with Sirtuin 2 inhibitory activity
  作者：Tianming Yang、Xiao Chen、Hai-xiao Jin、Gautam Sethi、Mei-Lin Go

  DOI：10.1016/j.ejmech.2014.12.027

  日期：2015.3

  Sirtuins are protein deacylases with regulatory roles in metabolism and stress response. Functionalized tetrahydro-1H-pyrido[4,3-b]indoles were identified as preferential sirtuin 2 inhibitors, with in vitro inhibitory potencies in the low micromolar concentrations (IC50 3-4 mu M) for the more promising candidates. The functional relevance of sirtuin inhibition was corroborated in western blots that showed hyperacetylation of p53 and alpha-tubulin in treated HepG2 and MDA-MB-231 cells. Molecular docking showed that the tetrahydropyridoindole scaffold was positioned in the NAD + pocket and the acetylated substrate channel of the sirtuin 2 protein by van der Waals/hydrophobic, H bonding and stacking interactions. Functionalized tetrahydropyridoindoles represent a novel class of sirtuin 2 inhibitors that could be further explored for its therapeutic potential. (C) 2014 Elsevier Masson SAS. All rights reserved.