2-(Allyl-propionyl-amino)-8-methoxy-1,2,3,4-tetrahydro-naphthalene-1-carboxylic acid methyl ester | 134465-85-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 2-(Allyl-propionyl-amino)-8-methoxy-1,2,3,4-tetrahydro-naphthalene-1-carboxylic acid methyl ester
• 英文别名: Methyl 8-methoxy-2-[propanoyl(prop-2-enyl)amino]-1,2,3,4-tetrahydronaphthalene-1-carboxylate
• CAS: 134465-85-3
• 化学式: C₁₉H₂₅NO₄
• 分子量: 331.412
• InChiKey: OJTDYPHOKKDROE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(Allyl-propionyl-amino)-8-methoxy-1,2,3,4-tetrahydro-naphthalene-1-carboxylic acid methyl ester 在 吡啶 、 lithium aluminium tetrahydride 、 potassium tert-butylate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 29.0h， 生成 (+/-)-1,2,3,4-tetrahydro-8-methoxy-1-methylene-N-2-propenyl-N-n-propylnaphthalenamine
  参考文献：
  名称：

  Centrally acting serotonergic agents. Synthesis and structure-activity relationships of C-1- or C-3-substituted derivatives of 8-hydroxy-2-(di-n-propylamino)tetralin

  摘要：

  The synthesis and structure-activity relationships (SAR) of C-1- or C-3-substituted derivatives of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) are described. These analogs were synthesized via alkylation of the tetralone derivatives followed by reductive amination. All of the analogs were inactive at the dopamine D2 receptor. Among the 8-OMe or 8-OH C-1,N-disubstituted analogs synthesized, the cis analogs were more potent in the 5-HT1A binding assay than the corresponding trans analogs. However, in the case of 1-(cyclopropylmethyl)-N-n-propyl analogs, the trans isomer has a slightly higher 5-HT1A affinity than its cis counterpart. The order of binding potency for C-1 substitution was found to be allyl > hydroxymethyl> n-propyl > cyclopropylmethyl much greater than carbomethoxy. Interestingly, the 5-OMe analogs were found to be inactive in both the 5-HT1A and dopamine D2 binding assays. In the C-3 allyl-substituted analogs, 5-HT1A agonist activity was found to be considerably lower. In these examples, the trans analogs showed weak 5-HT1A binding activity whereas the cis analogs were inactive. Analogs with C-1,N,N-trisubstitution also showed a marked decrease in 5-HT1A binding affinity. Overall, the SAR study showed that cis C-1 substitution maintains the 5-HT1A agonist activity of 8-OH-DPAT whereas trans C-1 substitution displays somewhat diminished activity. On the other hand, the trans C-3 substitution shows modest agonist activity whereas cis C-3 substitution removes the activity completely.

  DOI：

  10.1021/jm00058a003
• 作为产物：
  描述：

  丙酸酐 、 2-Allylamino-8-methoxy-1,2,3,4-tetrahydro-naphthalene-1-carboxylic acid methyl ester 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以84%的产率得到2-(Allyl-propionyl-amino)-8-methoxy-1,2,3,4-tetrahydro-naphthalene-1-carboxylic acid methyl ester
  参考文献：
  名称：

  Centrally acting serotonergic agents. Synthesis and structure-activity relationships of C-1- or C-3-substituted derivatives of 8-hydroxy-2-(di-n-propylamino)tetralin

  摘要：

  The synthesis and structure-activity relationships (SAR) of C-1- or C-3-substituted derivatives of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) are described. These analogs were synthesized via alkylation of the tetralone derivatives followed by reductive amination. All of the analogs were inactive at the dopamine D2 receptor. Among the 8-OMe or 8-OH C-1,N-disubstituted analogs synthesized, the cis analogs were more potent in the 5-HT1A binding assay than the corresponding trans analogs. However, in the case of 1-(cyclopropylmethyl)-N-n-propyl analogs, the trans isomer has a slightly higher 5-HT1A affinity than its cis counterpart. The order of binding potency for C-1 substitution was found to be allyl > hydroxymethyl> n-propyl > cyclopropylmethyl much greater than carbomethoxy. Interestingly, the 5-OMe analogs were found to be inactive in both the 5-HT1A and dopamine D2 binding assays. In the C-3 allyl-substituted analogs, 5-HT1A agonist activity was found to be considerably lower. In these examples, the trans analogs showed weak 5-HT1A binding activity whereas the cis analogs were inactive. Analogs with C-1,N,N-trisubstitution also showed a marked decrease in 5-HT1A binding affinity. Overall, the SAR study showed that cis C-1 substitution maintains the 5-HT1A agonist activity of 8-OH-DPAT whereas trans C-1 substitution displays somewhat diminished activity. On the other hand, the trans C-3 substitution shows modest agonist activity whereas cis C-3 substitution removes the activity completely.

  DOI：

  10.1021/jm00058a003