2-{2-[3-(5-fluoro-1H-indol-3-yl)propylamino]ethoxy}-6-nitrophenylamine | 246019-16-9

• 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-{2-[3-(5-fluoro-1H-indol-3-yl)propylamino]ethoxy}-6-nitrophenylamine
• 英文别名: 2-[2-[3-(5-fluoro-1H-indol-3-yl)propylamino]ethoxy]-6-nitroaniline
• CAS: 246019-16-9
• 化学式: C₁₉H₂₁FN₄O₃
• 分子量: 372.399
• InChiKey: YGORSAJLTJXKON-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  109
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-{2-[3-(5-fluoro-1H-indol-3-yl)propylamino]ethoxy}-6-nitrophenylamine 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以82%的产率得到3-{2-[3-(5-fluoro-1H-indol-3-yl)propylamino]ethoxy}benzene-1,2-diamine
  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
• 作为产物：
  描述：

  2-氨基-3-硝基苯酚 在 potassium carbonate 、 三乙胺 作用下， 以 二甲基亚砜 、 丁酮 为溶剂， 反应 36.0h， 生成 2-{2-[3-(5-fluoro-1H-indol-3-yl)propylamino]ethoxy}-6-nitrophenylamine
  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
  申请人：Wyeth

  公开号：EP1068199B1

  公开（公告）日：2002-11-13
• US6150533A
  申请人：——

  公开号：US6150533A

  公开（公告）日：2000-11-21
• [EN] N-ARYLOXYETHYL-INDOLY-ALKYLAMINES FOR THE TREATMENT OF DEPRESSION<br/>[FR] N-ARYLOXYETHYLE-INDOLY-ALKYLAMINES POUR LE TRAITEMENT DE LA DEPRESSION
  申请人：——

  公开号：WO1999051591A2

  公开（公告）日：1999-10-14

  [EN] Compounds effective in treating disorders of the serotonin-affected neurological systems are provided, such compounds having formula (I), wherein: R1 is hydrogen, lower alkyl, phenyl, or substituted phenyl; X and Y together complete a lactam, imidazole, imidazolone, or thioimidazolone ring; Z is hydrogen, halogen, or lower alkoxy; W is hydrogen, halogen, lower alkoxy, lower alkyl, cyano, or a trifluoromethyl group; and n=2 to 5; or pharmaceutically acceptable salts thereof.
  [FR] L'invention concerne des composés efficaces pour le traitement des systèmes neurologiques présentant des troubles liés à la sérotonine. Ces composés sont représentés par la formule (I), dans laquelle R1 représente hydrogène, alkyle inférieur, phényle ou phényle substitué; X et Y forment un noyau lactame, imidazole, imidazolone ou thioimidazolone; Z représente hydrogène, halogène ou alcoxy inférieur; W représente hydrogène, halogène, alcoxy inférieur, alkyle inférieur, cyano ou un groupe trifluorométhyle: et n est un nombre de 2 à 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.