[3-(1H-Indol-3-yl)-propyl]-[2-(quinolin-8-yloxy)-ethyl]-amine

• 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: [3-(1H-Indol-3-yl)-propyl]-[2-(quinolin-8-yloxy)-ethyl]-amine
• 英文别名: 3-(1H-indol-3-yl)-N-(2-quinolin-8-yloxyethyl)propan-1-amine
• 化学式: C₂₂H₂₃N₃O
• 分子量: 345.444
• InChiKey: IRZUEVZANGAMPR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  49.9
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-吲哚丙酸 在 lithium aluminium tetrahydride 、 偶氮二甲酸二异丙酯 、 三苯基膦 、 N,N'-羰基二咪唑 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 26.0h， 生成 [3-(1H-Indol-3-yl)-propyl]-[2-(quinolin-8-yloxy)-ethyl]-amine
  参考文献：
  名称：

  Studies toward the Discovery of the Next Generation of Antidepressants. 3. Dual 5-HT_1A and Serotonin Transporter Affinity within a Class of N-Aryloxyethylindolylalkylamines

  摘要：

  N-Aryloxylethylindolealkylamines (5) having dual 5-HT transporter and 5-HT1A affinity are described. These compounds represent truncated analogues of our previously reported piperidinyl derivatives (3). Compounds in this investigation were found to have more similar affinities and functional activities for the 5-HT1A receptor and 5-HT transporter. Though 5-HT1A antagonism is not consistently observed throughout series 5, several molecular features were found to be essential to obtain high and balanced activities. The proper placement of a heteroatom in the aryl ring and the length of the linkage used to tether the indole moiety had significant influence on 5-HT1A and 5-HT transporter affinities. Introduction of a halogen into the aryl ring usually lowered intrinsic activity and in some cases led to full 5-HT1A antagonists. Compounds 33 and 34 were observed to be full 5-HT1A antagonists with K-i values of approximately 30 nM for the 5-HT1A receptor and K-i values of 5 and 0.5 nM for the 5-HT transporter, respectively. Unfortunately, similar to our previous series (3), compounds in this report also had high affinity for the alpha(1) receptor.

  DOI：

  10.1021/jm0304010

文献信息

• N-ARYLOXYETHYL-INDOLY-ALKYLAMINES FOR THE TREATMENT OF DEPRESSION (5-HT1A RECEPTOR ACTIVE AGENTS)
  申请人：AMERICAN HOME PRODUCTS CORPORATION

  公开号：EP1070050A1

  公开（公告）日：2001-01-24
• US6121307A
  申请人：——

  公开号：US6121307A

  公开（公告）日：2000-09-19
• US6291683B1
  申请人：——

  公开号：US6291683B1

  公开（公告）日：2001-09-18
• [EN] N-ARYLOXYETHYL-INDOLY-ALKYLAMINES FOR THE TREATMENT OF DEPRESSION (5-HT1A RECEPTOR ACTIVE AGENTS)<br/>[FR] N-ARYLOXYETHYL-INDOLY-ALKYLAMINES UTILISEES POUR LE TRAITEMENT DE LA DEPRESSION (PRINCIPES ACTIFS DE RECEPTEURS DU TYPE 5-HT1A)
  申请人：AMERICAN HOME PRODUCTS CORPORATION

  公开号：WO1999051575A1

  公开（公告）日：1999-10-14

  (EN) Compounds useful for alleviating symptoms of depression (5-HT1A receptor active agents) are provided which have formula (I), wherein: R1 is hydrogen, lower alkyl or aryl; R2 is hydrogen, lower alkyl, phenyl or substituted phenyl; X and Y are each, independently, hydrogen, lower alkyl, lower alkoxy, or halogen, or together combined with the carbon atoms to which they are attached to complete a cyclopentyl, cyclohexyl, phenyl, pyrrolyl, pyranyl, pyridinyl, dihydrofuranyl, furanyl, dioxanyl, oxazolyl or isoxazolyl group; Z is hydrogen, halogen or lower alkoxy; with the proviso that when X, Y or Z represent lower alkoxy, they are not present at the ortho position; W is hydrogen, halogen, lower alkyl, cyano or a trifluoromethyl group; and n is 2-5; or pharmaceutically acceptable salts thereof.(FR) L'invention concerne des composés servant à atténuer les symptômes de la dépression (principes actifs de récepteurs du type 5-HT1A). Ces composés sont représentés par la formule (I), dans laquelle R1 représente hydrogène, alkyle inférieur ou aryle; R2 représente hydrogène, alkyle inférieur, phényle ou phényle substitué; X et Y représentent chacun indépendamment hydrogène, alkyle inférieur, alcoxy inférieur ou halogène ou se combinent aux atomes de carbone auxquels ils sont liés, de façon à former un groupe cyclopentyle, cyclohexyle, phényle, pyrrolyle, pyranyle, pyridinyle, dihydrofuranyle, furanyle, dioxanyle, oxazolyle ou isoxazolyle; Z représente hydrogène, halogène ou alcoxy inférieur; à condition que lorsque X, Y ou Z représentent alcoxy inférieur, ils ne soient pas présents dans la position ortho; W représente hydrogène, halogène, alkyle inférieur, cyano ou un groupe trifluorométhyle; et n est compris entre 2 et 5. L'invention concerne également des sels pharmaceutiquement acceptables desdits composés.
• Studies toward the Discovery of the Next Generation of Antidepressants. 3. Dual 5-HT_1A and Serotonin Transporter Affinity within a Class of <i>N</i>-Aryloxyethylindolylalkylamines
  作者：Richard E. Mewshaw、Dahui Zhou、Ping Zhou、Xiaojie Shi、Geoffrey Hornby、Taylor Spangler、Rosemary Scerni、Deborah Smith、Lee E. Schechter、Terrance H. Andree

  DOI：10.1021/jm0304010

  日期：2004.7.1

  N-Aryloxylethylindolealkylamines (5) having dual 5-HT transporter and 5-HT1A affinity are described. These compounds represent truncated analogues of our previously reported piperidinyl derivatives (3). Compounds in this investigation were found to have more similar affinities and functional activities for the 5-HT1A receptor and 5-HT transporter. Though 5-HT1A antagonism is not consistently observed throughout series 5, several molecular features were found to be essential to obtain high and balanced activities. The proper placement of a heteroatom in the aryl ring and the length of the linkage used to tether the indole moiety had significant influence on 5-HT1A and 5-HT transporter affinities. Introduction of a halogen into the aryl ring usually lowered intrinsic activity and in some cases led to full 5-HT1A antagonists. Compounds 33 and 34 were observed to be full 5-HT1A antagonists with K-i values of approximately 30 nM for the 5-HT1A receptor and K-i values of 5 and 0.5 nM for the 5-HT transporter, respectively. Unfortunately, similar to our previous series (3), compounds in this report also had high affinity for the alpha(1) receptor.