cis-(3aR)-2,3,3a,4,5,9b-hexahydro-3-n-propyl-1H-benzindole-9-carboxylic acid chloride | 160756-98-9

• 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-3-n-propyl-1H-benzindole-9-carboxylic acid chloride
• 英文别名: (3aR,9bS)-3-propyl-1,2,3a,4,5,9b-hexahydrobenzo[e]indole-9-carbonyl chloride
• CAS: 160756-98-9
• 化学式: C₁₆H₂₀ClNO
• 分子量: 277.794
• InChiKey: ULZGEHAGIQXZMB-TZMCWYRMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  cis-(3aR)-2,3,3a,4,5,9b-hexahydro-3-n-propyl-1H-benzindole-9-carboxylic acid chloride 在 正丙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (3aR,9bS)-3-Propyl-2,3,3a,4,5,9b-hexahydro-1H-benzo[e]indole 、 (3aR,9bS)-3-Propyl-2,3,3a,4,5,9b-hexahydro-1H-benzo[e]indole-9-carboxylic acid propylamide
  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：

  二氧化碳 、 cis-(+/-)-2,3,3a,4,5,9b-hexahydro-9-bromo-3-(n-propyl)-1H-benz[e]indole 在 草酰氯 、 叔丁基锂 、 N,N-二甲基甲酰胺 作用下， 生成 cis-(3aR)-2,3,3a,4,5,9b-hexahydro-3-n-propyl-1H-benzindole-9-carboxylic acid chloride
  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