(S)-5-methoxy-2-(N-cyanomethyl-N-n-propylamino)tetralin | 244239-69-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: (S)-5-methoxy-2-(N-cyanomethyl-N-n-propylamino)tetralin
• CAS: 244239-69-8
• 化学式: C₁₆H₂₂N₂O
• 分子量: 258.363
• InChiKey: FFVHRTBDOXMXHY-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.79
• 重原子数：
  19.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  36.26
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (S)-5-methoxy-2-(N-cyanomethyl-N-n-propylamino)tetralin 在 sodium hydroxide 、 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 27.0h， 生成
  参考文献：
  名称：

  Synthesis and pharmacology of the enantiomers of the potential atypical antipsychotic agents 5-OMe-BPAT and 5-OMe-(2,6-di-OMe)-BPAT

  摘要：

  The optically pure enantiomers of the potential atypical antipsychotic agents 5-methoxy-2-[N-(2-benzamidoethyl)-N-n-propylamino]tetralin (5-OMe-BPAT, 5) and 5-methoxy-2-{N-[2-(2,6-dimethoxy)benzamidoethyl]-N-n-propylamino}tetralin [5-OMe-(2,6-di-OMe)-BPAT, 6] were synthesized and evaluated for their in vitro binding affinities at alpha(1)-, alpha(2)-, and beta-adrenergic, muscarinic, dopamine D-1, D-2A,D- and D-3, and serotonin 5-HT1A and 5-HT2 receptors. In addition, their intrinsic efficacies at serotonin 5-HT1A receptors were established in vitro. (S)- and (R)-5 had high affinities for dopamine D2A, D3, and serotonin 5-HT1A receptors: moderate affinities for alpha(1)-adrenergic and serotonin 5-HT2 receptors, and no affinity (K-i > 1000 nM) for the other receptor subtypes. (S)- and (R)-6 had lower affinities for the dopamine D-2A and the serotonin 5-HT1A receptor, compared to (S)- and (R)-5, and hence showed some selectivity for the dopamine D3 receptor. The interactions with the receptors were stereospecific, since the serotonin 5-HT1A receptor preferred the (S)-enantiomers, while the dopamine D-2A and D-2 receptors preferred the (R)-enantiomers of 5 and 6. The intrinsic efficacies at the serotonin 5-HT1A receptor were established by measuring their ability to inhibit VIP-induced cAMP production in GH(4)ZD10 cells expressing serotonin 5-HT1A receptors. Both enantiomers of 5 behaved as full serotonin 5-HT1A receptor agonists in this assay, while both enantiomers of 6 behaved as weak partial agonists. The potential antipsychotic properties of (S)- and (R)-5 were evaluated by establishing their ability to inhibit d-amphetamine-induced locomotor activity in rats, while their propensity to induce extrapyramidal side-effects (EPS) in man was evaluated by determining their ability to induce catalepsy in rats. Whereas (R)-5 was capable of blocking d-amphetamine-induced locomotor activity, indicative of dopamine D-2 receptor antagonism, (S)-5 even enhanced the effect of d-amphetamine, suggesting that this compound has dopamine D-2 receptor-stimulating properties. Since both enantiomers also were devoid of cataleptogenic activity, they are interesting candidates for further exploring the dopamine D-2/serotonin 5-HT1A hypothesis of atypical antipsychotic drug action. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00073-5
• 作为产物：
  描述：

  (S)-2-氨基-5-甲氧基四氢萘盐酸盐 在 sodium hydroxide 、 lithium aluminium tetrahydride 、 potassium carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 、 丙酮 为溶剂， 反应 84.0h， 生成 (S)-5-methoxy-2-(N-cyanomethyl-N-n-propylamino)tetralin
  参考文献：
  名称：

  Synthesis and pharmacology of the enantiomers of the potential atypical antipsychotic agents 5-OMe-BPAT and 5-OMe-(2,6-di-OMe)-BPAT

  摘要：

  The optically pure enantiomers of the potential atypical antipsychotic agents 5-methoxy-2-[N-(2-benzamidoethyl)-N-n-propylamino]tetralin (5-OMe-BPAT, 5) and 5-methoxy-2-{N-[2-(2,6-dimethoxy)benzamidoethyl]-N-n-propylamino}tetralin [5-OMe-(2,6-di-OMe)-BPAT, 6] were synthesized and evaluated for their in vitro binding affinities at alpha(1)-, alpha(2)-, and beta-adrenergic, muscarinic, dopamine D-1, D-2A,D- and D-3, and serotonin 5-HT1A and 5-HT2 receptors. In addition, their intrinsic efficacies at serotonin 5-HT1A receptors were established in vitro. (S)- and (R)-5 had high affinities for dopamine D2A, D3, and serotonin 5-HT1A receptors: moderate affinities for alpha(1)-adrenergic and serotonin 5-HT2 receptors, and no affinity (K-i > 1000 nM) for the other receptor subtypes. (S)- and (R)-6 had lower affinities for the dopamine D-2A and the serotonin 5-HT1A receptor, compared to (S)- and (R)-5, and hence showed some selectivity for the dopamine D3 receptor. The interactions with the receptors were stereospecific, since the serotonin 5-HT1A receptor preferred the (S)-enantiomers, while the dopamine D-2A and D-2 receptors preferred the (R)-enantiomers of 5 and 6. The intrinsic efficacies at the serotonin 5-HT1A receptor were established by measuring their ability to inhibit VIP-induced cAMP production in GH(4)ZD10 cells expressing serotonin 5-HT1A receptors. Both enantiomers of 5 behaved as full serotonin 5-HT1A receptor agonists in this assay, while both enantiomers of 6 behaved as weak partial agonists. The potential antipsychotic properties of (S)- and (R)-5 were evaluated by establishing their ability to inhibit d-amphetamine-induced locomotor activity in rats, while their propensity to induce extrapyramidal side-effects (EPS) in man was evaluated by determining their ability to induce catalepsy in rats. Whereas (R)-5 was capable of blocking d-amphetamine-induced locomotor activity, indicative of dopamine D-2 receptor antagonism, (S)-5 even enhanced the effect of d-amphetamine, suggesting that this compound has dopamine D-2 receptor-stimulating properties. Since both enantiomers also were devoid of cataleptogenic activity, they are interesting candidates for further exploring the dopamine D-2/serotonin 5-HT1A hypothesis of atypical antipsychotic drug action. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00073-5