1-(2-(N,N-Dimethylamino)ethyl)-6-(N-methyl-4-hydroxy-4-piperidinyl)-1H-indole | 281202-74-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-(2-(N,N-Dimethylamino)ethyl)-6-(N-methyl-4-hydroxy-4-piperidinyl)-1H-indole
• 英文别名: 4-[1-[2-(Dimethylamino)ethyl]indol-6-yl]-1-methylpiperidin-4-ol
• CAS: 281202-74-2
• 化学式: C₁₈H₂₇N₃O
• 分子量: 301.432
• InChiKey: PHNQDOBOVYNSPB-UHFFFAOYSA-N

物化性质

• 沸点：
  472.6±45.0 °C(Predicted)
• 密度：
  1.11±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  31.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2-(N,N-Dimethylamino)ethyl)-6-(N-methyl-4-hydroxy-4-piperidinyl)-1H-indole 在 三氟乙酸 作用下， 以 四氢呋喃 为溶剂， 生成 N,N-dimethyl-2-[6-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)indol-1-yl]ethanamine
  参考文献：
  名称：

  Design, synthesis and biological activity of novel dimethyl-{2-[6-substituted-indol-1-yl]-ethyl}-amine as potent, selective, and orally-Bioavailable 5-HT 1D agonists

  摘要：

  A novel series of highly potent human 5-HT1D agonists, dimethyl-{2-[6-substituted-indol-1-yl]-ethyl}-amine, was synthesized. Structure-activity relationship (SAR) investigation revealed 4-[1-(2-dimethylamino-ethyl)-1H-indol-6-yl]-tetrahydro-thiopyran-4-ol, 11b (ALX-2732), as a potent (K-i = 2.4 nM) agonist at the human 5-HT1D receptor with good selectivity over the other serotonin receptor subtypes. This compound demonstrated favorable in vitro metabolic stability in human and rat liver microsomes and was found to be orally bioavailable in rats (F-po = 51%) (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.09.025
• 作为产物：
  描述：

  6-溴吲哚 在 叔丁基锂 、 potassium hydride 、 sodium hydride 、 二异丁基氢化铝 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 1-(2-(N,N-Dimethylamino)ethyl)-6-(N-methyl-4-hydroxy-4-piperidinyl)-1H-indole
  参考文献：
  名称：

  Design, synthesis and biological activity of novel dimethyl-{2-[6-substituted-indol-1-yl]-ethyl}-amine as potent, selective, and orally-Bioavailable 5-HT 1D agonists

  摘要：

  A novel series of highly potent human 5-HT1D agonists, dimethyl-{2-[6-substituted-indol-1-yl]-ethyl}-amine, was synthesized. Structure-activity relationship (SAR) investigation revealed 4-[1-(2-dimethylamino-ethyl)-1H-indol-6-yl]-tetrahydro-thiopyran-4-ol, 11b (ALX-2732), as a potent (K-i = 2.4 nM) agonist at the human 5-HT1D receptor with good selectivity over the other serotonin receptor subtypes. This compound demonstrated favorable in vitro metabolic stability in human and rat liver microsomes and was found to be orally bioavailable in rats (F-po = 51%) (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.09.025

文献信息

• N-alkylamino-indoles for the treatment of migraine
  申请人：NPS Allelix Corp.

  公开号：US06380242B1

  公开（公告）日：2002-04-30

  The present invention is directed to compounds useful in the treatment of migraine which have the general formula (II).

  本发明涉及一种具有通式（II）的化合物，用于治疗偏头痛。
• [EN] INDOLE AND INDOLIZIDINE DERIVATIVES FOR THE TREATMENT OF MIGRAINE<br/>[FR] DERIVES INDOLE ET INDOLIZIDINE PERMETTANT DE TRAITER LES MIGRAINES
  申请人：ALLELIX BIOPHARMA

  公开号：WO2000038677A1

  公开（公告）日：2000-07-06

  Described herein are compounds useful in the treatment of migraine, which have general formula (I) wherein: X is selected from the group consisting of N, CH; R1 represents a 5- to 7-membered monocyclic or benzo-fused heterocyclic ring, which may be unsaturated, and which may contain one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, amino and mono- or di-lower alkyl amino; Ak represents a C1-3alkylene chain which may be substituted with R2, where R2 represents lower alkyl; R3 and R4 are independently selected from the group consisting of H, lower alkyl, lower alkenyl, cycloalkyl and optionally-substituted benzyl; or one pair of R2 and R3 or R3 and R4 together may form an alkylene or alkenylene bridge which, with the nitrogen atom, form a 3- to 7-membered ring which may contain one or more substituents selected from the group consisting of lower alkyl, hydroxy, hydroxymethyl, alkoxymethyl, amino and substituted amino; R5 is selected from the group consisting of H, lower alkyl and a 4- to 7-membered carbocyclic or heterocyclic group, which may be unsaturated; and a salt, solvate or prodrug thereof. Also disclosed are novel compounds of formula (II) wherein: X is selected from the group consisting of N and CH; R6 represents a 5- to 7-membered monocyclic or benzo-fused heterocyclic ring, which may be unsaturated, and which may contain one or more substituents selected from the group consisting of lower alkyl, hydroxy, lower alkoxy, amino and mono- or di-lower alkyl amino; Ak represents a C1-3alkylene chain which may be substituted with R7, where R7 represents lower alkyl; R8 and R9 are independently selected from the group consisting of H, lower alkyl, lower alkenyl, cycloalkyl and optionally-substituted benzyl; R10 is selected from the group consisting of H, lower alkyl and a 4- to 7-membered carbocyclic or heterocyclic group, which may be unsaturated, and a salt, solvate or prodrug thereof.

  本文介绍了一些用于治疗偏头痛的化合物，其具有一般式 (I)，其中：X选自N，CH组成的群；R1表示一个5-至7-成员的单环或苯并螺环，可以不饱和，并且可以含有一个或多个取代基，所述取代基选自较低烷基，羟基，较低烷氧基，氨基和单个或双个较低烷基氨基；Ak表示可以用R2取代的C1-3烷基链，其中R2表示较低烷基；R3和R4独立地选自H，较低烷基，较低烯基，环烷基和可选取代的苄基；或者R2和R3或R3和R4中的一对可以一起形成烷基或烯基桥，与氮原子一起形成一个3-至7-成员的环，所述环可以含有一个或多个取代基，所述取代基选自较低烷基，羟基，羟甲基，烷氧甲基，氨基和取代氨基；R5选自H，较低烷基和一个4-至7-成员的碳环或杂环基，可以不饱和；以及其盐，溶剂化合物或前药。本文还公开了新的化合物，其具有式（II），其中：X选自N和CH组成的群；R6表示一个5-至7-成员的单环或苯并螺环，可以不饱和，并且可以含有一个或多个取代基，所述取代基选自较低烷基，羟基，较低烷氧基，氨基和单个或双个较低烷基氨基；Ak表示可以用R7取代的C1-3烷基链，其中R7表示较低烷基；R8和R9独立地选自H，较低烷基，较低烯基，环烷基和可选取代的苄基；R10选自H，较低烷基和一个4-至7-成员的碳环或杂环基，可以不饱和；以及其盐，溶剂化合物或前药。
• Use of N-alkylamino-heterocylic compounds for the treatment of migraine
  申请人：NPS Allexlix Corp.

  公开号：US20020169322A1

  公开（公告）日：2002-11-14

  Described are compounds having formula I or II: 1 wherein: X is N, CH or C-lower alkyl; R 1 represents a 5 to 7-membered monocyclic or benzo-fused heterocyclic ring, Ak represents a C 1-3 alkylene chain; R 3 and R 4 are H, lower alkyl, lower alkenyl or optionally-substituted benzyl; or one pair of R 2 , R 3 or R 3 , R 4 together may form an alkylene or alkenylene bridge which, with the nitrogen atom, form a 3- to 7-membered ring; R 5 is H, lower alkyl or a 4- to 7-membered carbocyclic or heterocyclic group; R 6 represents a 5 to 7-membered monocyclic or benzo-fused heterocyclic ring; R 8 and R 9 are H, lower alkyl, lower alkenyl or optionally-substituted benzyl; R 10 is H, lower alkyl or a 4- to 7-membered carbocyclic or heterocyclic group; and a salt, solvate or prodrug thereof.

  描述了具有公式I或II的化合物：1其中：X为N、CH或C-较低烷基；R1表示5至7成员的单环或苯并嵌杂环；Ak表示C1-3烷基链；R3和R4为H、较低烷基、较低烯基或可选取代苄基；或者R2、R3或R3、R4中的一对可以共同形成与氮原子一起形成3至7成员环的烷基或烯基桥；R5为H、较低烷基或4至7成员的碳环或杂环基团；R6表示5至7成员的单环或苯并嵌杂环；R8和R9为H、较低烷基、较低烯基或可选取代苄基；R10为H、较低烷基或4至7成员的碳环或杂环基团；以及其盐、溶剂化物或前药。
• INDOLE AND INDOLIZIDINE DERIVATIVES FOR THE TREATMENT OF MIGRAINE
  申请人：NPS Allelix Corp.

  公开号：EP1140074A1

  公开（公告）日：2001-10-10
• US6380242B1
  申请人：——

  公开号：US6380242B1

  公开（公告）日：2002-04-30