cis-(3aR)-2,3,3a,4,5,9b-hexahydro-1H-benzindole-9-carboxamide | 147145-13-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: cis-(3aR)-2,3,3a,4,5,9b-hexahydro-1H-benzindole-9-carboxamide
• 英文别名: (3aR,9bS)-2,3,3a,4,5,9b-hexahydro-1H-benzo[e]indole-9-carboxamide
• CAS: 147145-13-9
• 化学式: C₁₃H₁₆N₂O
• 分子量: 216.283
• InChiKey: SNAKEQIDRIAHKP-MWLCHTKSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  55.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-氯丙炔 、 cis-(3aR)-2,3,3a,4,5,9b-hexahydro-1H-benzindole-9-carboxamide 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以67%的产率得到(3aR,9bS)-3-Prop-2-ynyl-2,3,3a,4,5,9b-hexahydro-1H-benzo[e]indole-9-carboxylic acid amide
  参考文献：
  名称：

  C-9 and N-Substituted Analogs of cis-(3aR)-(-)-2,3,3a,4,5,9b-Hexahydro-3-propyl-1H-benz[e]indole-9-carboxamide: 5-HT1A Receptor Agonists with Various Degrees of Metabolic Stability

  摘要：

  Closely related analogs of the 5-HT1A receptor agonist cis-(3aR)-(-)-2,3,3a,4,5,9b-hexahydro-3-propyl-LH-benz[e]indole-9-carboxamide (1, U93385) were synthesized and pharmacologically evaluated. 9-Carboxamide analogs with varied nitrogen substitution (R(2)) were synthesized, and their serotonergic activity was evaluated in vitro and in vivo. Many of these compounds were incubated in the presence of rat hepatocytes, and the metabolic stability in vitro was compared to that of compound 1. Only the N-methyl and N-ethyl analogs ((-)-5a and (-)-5b) were more stable than compound 1, indicating that N-dealkylation is a major route of metabolism in this series. In addition, these analogs were found to be partial 5-HT1A receptor agonists in vivo. Modifications were also made to the carboxamide functionality of compound 1 (R(1) in 2) to yield substituted amides or ketones. Among these analogs, the methyl ketone (-)-15a was found to be a 5-HT1A agonist with full intrinsic activity in vivo and was approximately 20 times more potent than compound 1 and 5 times more potent than 8-OH-DPAT.

  DOI：

  10.1021/jm00004a018
• 作为产物：
  描述：

  cis-(3aR)-2,3,3a,4,5,9b-hexahydro-3-(1(R)-methylbenzyl)-1H-benzindole-9-carboxamide 在 palladium on activated charcoal 甲酸铵 作用下， 以 甲醇 为溶剂， 反应 48.0h， 以58%的产率得到cis-(3aR)-2,3,3a,4,5,9b-hexahydro-1H-benzindole-9-carboxamide
  参考文献：
  名称：

  C-9 and N-Substituted Analogs of cis-(3aR)-(-)-2,3,3a,4,5,9b-Hexahydro-3-propyl-1H-benz[e]indole-9-carboxamide: 5-HT1A Receptor Agonists with Various Degrees of Metabolic Stability

  摘要：

  Closely related analogs of the 5-HT1A receptor agonist cis-(3aR)-(-)-2,3,3a,4,5,9b-hexahydro-3-propyl-LH-benz[e]indole-9-carboxamide (1, U93385) were synthesized and pharmacologically evaluated. 9-Carboxamide analogs with varied nitrogen substitution (R(2)) were synthesized, and their serotonergic activity was evaluated in vitro and in vivo. Many of these compounds were incubated in the presence of rat hepatocytes, and the metabolic stability in vitro was compared to that of compound 1. Only the N-methyl and N-ethyl analogs ((-)-5a and (-)-5b) were more stable than compound 1, indicating that N-dealkylation is a major route of metabolism in this series. In addition, these analogs were found to be partial 5-HT1A receptor agonists in vivo. Modifications were also made to the carboxamide functionality of compound 1 (R(1) in 2) to yield substituted amides or ketones. Among these analogs, the methyl ketone (-)-15a was found to be a 5-HT1A agonist with full intrinsic activity in vivo and was approximately 20 times more potent than compound 1 and 5 times more potent than 8-OH-DPAT.

  DOI：

  10.1021/jm00004a018

文献信息

• C-9 and N-Substituted Analogs of cis-(3aR)-(-)-2,3,3a,4,5,9b-Hexahydro-3-propyl-1H-benz[e]indole-9-carboxamide: 5-HT1A Receptor Agonists with Various Degrees of Metabolic Stability
  作者：Susanne R. Haadsma-Svensson、Kjell Svensson、Neil Duncan、Martin W. Smith、Chiu-Hong Lin

  DOI：10.1021/jm00004a018

  日期：1995.2

  Closely related analogs of the 5-HT1A receptor agonist cis-(3aR)-(-)-2,3,3a,4,5,9b-hexahydro-3-propyl-LH-benz[e]indole-9-carboxamide (1, U93385) were synthesized and pharmacologically evaluated. 9-Carboxamide analogs with varied nitrogen substitution (R(2)) were synthesized, and their serotonergic activity was evaluated in vitro and in vivo. Many of these compounds were incubated in the presence of rat hepatocytes, and the metabolic stability in vitro was compared to that of compound 1. Only the N-methyl and N-ethyl analogs ((-)-5a and (-)-5b) were more stable than compound 1, indicating that N-dealkylation is a major route of metabolism in this series. In addition, these analogs were found to be partial 5-HT1A receptor agonists in vivo. Modifications were also made to the carboxamide functionality of compound 1 (R(1) in 2) to yield substituted amides or ketones. Among these analogs, the methyl ketone (-)-15a was found to be a 5-HT1A agonist with full intrinsic activity in vivo and was approximately 20 times more potent than compound 1 and 5 times more potent than 8-OH-DPAT.