(8-Methoxy-3,4-dihydro-naphthalen-2-yl)-dipropyl-amine | 1026347-30-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (8-Methoxy-3,4-dihydro-naphthalen-2-yl)-dipropyl-amine
• 英文别名: 8-methoxy-N,N-dipropyl-3,4-dihydronaphthalen-2-amine
• CAS: 1026347-30-7
• 化学式: C₁₇H₂₅NO
• 分子量: 259.392
• InChiKey: JOYRGCIAWOUHQH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (8-Methoxy-3,4-dihydro-naphthalen-2-yl)-dipropyl-amine 在 氢溴酸 、 diethylzinc 作用下， 以 正己烷 、 正戊烷 为溶剂， 反应 3.0h， 生成 7-(dipropylamino)-7,8-methano-5,6,7,8-tetrahydronaphth-1-ol
  参考文献：
  名称：

  Phenolic derivatives of 1,2-methano-N,N-dipropyl-1,2,3,4-tetrahydronaphth-2-ylamine. Structural hybrids of 2-aminotetralin- and phenylcyclopropylamine-derived 5-HT1A-receptor agonists

  摘要：

  Three phenolic derivatives of 1,2-methano-N,N-dipropyl- 1,2,3,4-tetrahydronaphth-2-ylamine 6-8 were synthesized as structural hybrids of the potent 5-HT1A-receptor agonist 8-OH-DPAT 1 and 2 related phenolic phenylcyclopropylamines 4 and 5. The new compounds were assayed for 5-HT1A-receptor affinity and efficacy in vitro. Hybrids 6 and 7 were considered to be inactive but 8 had a K(i) value of 130 nM for [H-3]-8-OH-DPAT labelled 5-HT1A-receptors and produced an inhibition of the cAMP-production in the VIP-stimulated adenylyl cyclase assay. Thus, 8 is able to bind to and stimulate 5-HT1A-receptors. The results are discussed in relation to a previously described 3-D model for 5-HT1A-receptor agonists.

  DOI：

  10.1016/0223-5234(93)90126-y
• 作为产物：
  描述：

  8-甲氧基-3,4-二氢-1H-2-萘酮 、 二正丙胺 在 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 反应 48.0h， 生成 (8-Methoxy-3,4-dihydro-naphthalen-2-yl)-dipropyl-amine
  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

文献信息

• 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
  作者：Chiu Hong Lin、Susanne R. Haadsma-Svensson、Robert A. Lahti、Robert B. McCall、Montford F. Piercey、Peggy J. K. D. Schreur、Philip F. VonVoigtlander、Connie G. Chidester

  DOI：10.1021/jm00058a003

  日期：1993.3

  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.
• Phenolic derivatives of 1,2-methano-N,N-dipropyl-1,2,3,4-tetrahydronaphth-2-ylamine. Structural hybrids of 2-aminotetralin- and phenylcyclopropylamine-derived 5-HT1A-receptor agonists
  作者：J Vallgårda、LE Arvidsson、BE Svensson、CJ Fowler、U Hacksell

  DOI：10.1016/0223-5234(93)90126-y

  日期：1993.1

  Three phenolic derivatives of 1,2-methano-N,N-dipropyl- 1,2,3,4-tetrahydronaphth-2-ylamine 6-8 were synthesized as structural hybrids of the potent 5-HT1A-receptor agonist 8-OH-DPAT 1 and 2 related phenolic phenylcyclopropylamines 4 and 5. The new compounds were assayed for 5-HT1A-receptor affinity and efficacy in vitro. Hybrids 6 and 7 were considered to be inactive but 8 had a K(i) value of 130 nM for [H-3]-8-OH-DPAT labelled 5-HT1A-receptors and produced an inhibition of the cAMP-production in the VIP-stimulated adenylyl cyclase assay. Thus, 8 is able to bind to and stimulate 5-HT1A-receptors. The results are discussed in relation to a previously described 3-D model for 5-HT1A-receptor agonists.