(+/-)-methyl 2-(dipropylamino)tetralin-8-carboxylate | 124688-32-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (+/-)-methyl 2-(dipropylamino)tetralin-8-carboxylate
• 英文别名: 2-Dipropylamino-8-methoxycarbonyl-1,2,3,4-tetrahydronaphthalene；methyl 7-(dipropylamino)-5,6,7,8-tetrahydronaphthalene-1-carboxylate
• CAS: 124688-32-0
• 化学式: C₁₈H₂₇NO₂
• 分子量: 289.418
• InChiKey: PAAKORCQGYIBPE-UHFFFAOYSA-N

物化性质

• 沸点：
  415.6±45.0 °C(Predicted)
• 密度：
  1.04±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (+/-)-methyl 2-(dipropylamino)tetralin-8-carboxylate 在 ammonium hydroxide 、 sodium hydroxide 、 氯化亚砜 作用下， 以 甲醇 为溶剂， 反应 5.0h， 生成 (+/-)-8-carbamoyl-2-(dipropylamino)tetralin
  参考文献：
  名称：

  2-（二丙基氨基）四氢化萘的衍生物：C8取代基对与5-HT1A受体相互作用的影响。

  摘要：

  制备了一系列其中C8取代基不同的2-（二丙基氨基）四氢萘衍生物，并进行了药理学评价，以探讨C8取代基在基于2-氨基四氢萘的配体与血清素（5-HT1A）受体相互作用中的重要性。通过8-羟基-2-（二丙基氨基）四氢化萘（8-OH-DPAT，1）的对映异构体的三平面的钯催化反应制备对映纯衍生物。通过与[3H] -8-OH-DPAT在大鼠海马和皮层组织中的竞争实验，评估了化合物对5-HT1A受体的亲和力。另外，通过在大鼠中使用生化和行为测定，评估了化合物在体内对中心5-HT和多巴胺受体的刺激活性。除了没有5-HT1A受体亲和力的羧基取代的衍生物外，这些化合物对5-HT1A受体具有中等至高的亲和力（K（i）值在0.7到130 nM之间）。出乎意料的是，尽管几种衍生物具有相当高的5-HT1A受体亲和力，但它们在体内没有产生任何明显的作用。但是，甲氧基羰基和乙酰基取代的衍生物在体内是有效的5-HT1A受

  DOI：

  10.1021/jm00078a012
• 作为产物：
  描述：

  2-溴苯乙酰氯 在 platinum(IV) oxide 正丁基锂 、 三氯化铝 、 草酸氯化物 、 氢气 、 对甲苯磺酸 、 二环己胺 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 98.33h， 生成 (+/-)-methyl 2-(dipropylamino)tetralin-8-carboxylate
  参考文献：
  名称：

  Novel [(diazomethyl)carbonyl]-1,2,3,4-tetrahydronaphthalene derivatives as potential photoaffinity ligands for the 5-HT1A receptor

  摘要：

  The photolabile (diazomethyl)carbonyl function was introduced into the 8-position of 2-(N,N-di-n-propyl-amino)-1,2,3,4-tetrahydronaphthalene in three ways, resulting in the ether 8-[[(diazomethyl)carbonyl]methoxy]-2-(N,N-di-n-propylamino)-1,2,3,4- tetrahydronaphthalene (2), the ester 8-(diazoacetoxy)-2-(N,N-di-n-propyl-amino)-1,2,3,4- tetrahydronaphthalene (3), and the ketone 8-[(diazomethyl)carbonyl]-2-(N,N-di-n-propylamino)- 1,2,3,4-tetrahydronaphthalene (4). Specific binding of these compounds at the 5-hydroxytryptamine1A sites in rat brain membranes labeled with 1 nM [3H]-8-hydroxy-2-(N,N-di-n-propylamino)- 1,2,3,4-tetrahydronaphthalene (8-OH-DPAT) showed IC50 values of ca. 75, 125, and 25 nM, respectively, for the three compounds. Photolysis of methanolic solutions of 2-4 in the absence of receptor proteins lead in each case to an abundance of Wolff-rearranged products. In the case of ether 2, subsequent beta-elimination to 8-OH-DPAT removed this compound from serious consideration as a photoaffinity ligand. Ester 3 and ketone 4 were photolysed in vitro. Whereas ester 3 was ineffective in decreasing the specific binding of [3H]-8-OH-DPAT, ketone 4 decreased 40% of the specific binding of [3H]-8-OH-DPAT in the presence (but not the absence) of ultraviolet light. Thus this ketone emerges from these studies as a good candidate for a photoaffinity label for the 5-hydroxytrypatamine1A receptor.

  DOI：

  10.1021/jm00165a011

文献信息

• Ring-substituted 2-amino-1,2,3,4-tetra-hydronaphthalenes
  申请人：Eli Lilly and Company

  公开号：US05389687A1

  公开（公告）日：1995-02-14

  The present invention provides novel ring-substituted 2-amino-1,2,3,4-tetrahydronaphthalenes which exhibit binding activity at the serotonin 1A receptor.

  本发明提供了一种新型的环替代的2-氨基-1,2,3,4-四氢萘烯衍生物，其在5-羟色胺1A受体上表现出结合活性。
• Isoxazole derivatives for the treatment of irritable bowel syndrome
  申请人：ELI LILLY AND COMPANY

  公开号：EP0579507A1

  公开（公告）日：1994-01-19

  Provided is a method of treating Irritable Bowel Syndrome (IBS) using a series of isoxazole derivatives that have both 5-HT1A agonist and M1 muscarinic activities, and formulations suitable therefor.

  本发明提供了一种利用一系列同时具有 5-HT1A 激动剂和 M1 肌松素活性的异噁唑衍生物治疗肠易激综合征（IBS）的方法，以及适用于该方法的制剂。
• Ring-substituted 2-amino-1,2,3,4-tetra-hydronaphthalenes and 3-aminochromanes
  申请人：ELI LILLY AND COMPANY

  公开号：EP0712837A2

  公开（公告）日：1996-05-22

  The present invention provides novel ring-substituted 2-amino-1,2,3,4-tetrahydronaphthalenes and 3-aminochromanes which exhibit binding activity at the serotonin 1A receptor.

  本发明提供了新型环取代的 2-氨基-1,2,3,4-四氢萘和 3-氨基色烷，它们在血清素 1A 受体上表现出结合活性。
• C8-Substituted derivatives of 2-(dipropylamino)tetralin: exploration of the effect of C8-aryl and heteroaryl substituents on the interaction with 5-HT1A-receptor
  作者：Y Liu、L Cortizo、H Yu、BE Svensson、T Lewander、U Hacksell

  DOI：10.1016/0223-5234(96)88236-5

  日期：1995.1

  In order to further explore the structure-activity relationships of serotonergic 2-aminotetralin derivatives, a total of 12 aryl and heteroaryl substituents have been introduced in the C8-position of 2-(dipropylamino)tetralin. The affinity of the compounds was studied by competition experiments with [H-3]-8-OH-DPAT in rat-brain tissue. In addition, the effects of the compounds were assessed in vivo using biochemical and behavioral tests in rats. Although all the novel derivatives had fairly high affinities for the 5-HT1A receptors, several compounds failed to produce biochemical or behavioral effects indicative of 5-HT1A-receptor stimulation. In addition, they did not appear to be 5-HT1A-receptor antagonists. Hence, the apparent inactivity in vivo may be due to pharmacokinetic factors such as extensive metabolism or poor ability to pass the blood-brain barrier. However, a few compounds in the present series, such as (S)-8-(2-furyl)-2-(dipropylamino)tetralin did produce most of the in vivo pharmacological actions typical of 5-HT1A receptor agonists.
• KLINE, TONI B.;NELSON, DAVID L.;NAMBOODIRI, KRISHNAN, J. MED. CHEM., 33,(1990) N, C. 950-955
  作者：KLINE, TONI B.、NELSON, DAVID L.、NAMBOODIRI, KRISHNAN

  DOI：——

  日期：——