1-(3-bromopropyl)-5-methoxy-1,2,3,4-tetrahydronaphthalene | 161923-64-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 1-(3-bromopropyl)-5-methoxy-1,2,3,4-tetrahydronaphthalene
• CAS: 161923-64-4
• 化学式: C₁₄H₁₉BrO
• 分子量: 283.208
• InChiKey: IGUSLUYQABDGGJ-UHFFFAOYSA-N

物化性质

• 沸点：
  366.5±35.0 °C(Predicted)
• 密度：
  1.244±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-(3-bromopropyl)-5-methoxy-1,2,3,4-tetrahydronaphthalene 在 N-溴代丁二酰亚胺(NBS) 、 potassium carbonate 、 过氧化苯甲酰 作用下， 以 四氯化碳 、 乙腈 为溶剂， 反应 15.0h， 生成 [3-(5-Methoxy-naphthalen-1-yl)-propyl]-[2-(pyridin-2-yloxy)-ethyl]-amine
  参考文献：
  名称：

  trans-4-[4-(Methoxyphenyl)cyclohexyl]-1-arylpiperazines:  A New Class of Potent and Selective 5-HT_1A Receptor Ligands as Conformationally Constrained Analogues of 4-[3-(5-Methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]-1- arylpiperazines

  摘要：

  The present paper concerns the influence of conformational parameters on the recognition by rat 5-HT1A receptors of derivatives 4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]-1-(2-pyridinyl)piperazine (1a) and 3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-N-[2-(2-pyridyloxy)ethyl]propanamine (3b), two highly potent and selective 5-HT1A receptor ligands. Fifteen corresponding flexible and rigid analogues were prepared following several synthetic routes and were tested in binding assays with radioligands at 5-HT1A, D-2, and alpha (1) receptors from rat brain membranes. Among the new derivatives emerged trans-4-[4-(3-methoxyphenyl)-cyclohexyl]-1-(2-pyridinyl)piperazine (trans-8a) and trans-N-[4-(3-methoxyphenyl)cyclohexyl]-2-(2-pyridyloxy)ethylamine (trans-8b). These compounds can be-considered as conformationally constrained analogues of compounds 1a and 3a, respectively. In fact, compounds trans-8a and trans-8b showed a marked enhancement in 5-HT1A receptor affinity when compared to the corresponding cis isomers. Because compound trans-8a was a potent and selective 5-HT1A ligand (K-i, nM: 5-HT1A = 0.028, D-2 = 2194, alpha (1) = 767), it was chosen as a lead to prepare other analogues that were tested at 5-HT1A, D-2, and alpha (1) receptors from rat brain membranes, showing high affinity at the 5-HT1A and selectivity vs D-2 and alpha (1) receptors. Selected compounds were tested for their affinity at the human cloned 5-HT1A, alpha (1a), alpha (1b), alpha (1d) receptor subtypes. They were also submitted to the [S-35]GTP gammaS binding assay stimulating the 5-HT1A receptor-mediated G-protein activation, therefore behaving as full or as partial agonists. Finally, the ability of iv administration of trans-8a to induce fore-paw treading in rats was evaluated in comparison with 8-OH-DPAT. Although the affinity (K-i) and in vitro activity (pD'(2)) of trans-8a at the 5-HT1A receptor were higher than those of 8-OH-DPAT, the compound was less potent than the reference standard in inducing the symptom.

  DOI：

  10.1021/jm010866v
• 作为产物：
  描述：

  1-cyclopropyl-5-methoxy-1,2,3,4-tetrahydronaphthalen-1-ol 在 5%-palladium/activated carbon 氢溴酸 、 溶剂黄146 、 氢气 作用下， 以 水 、 甲醇 为溶剂， 生成 1-(3-bromopropyl)-5-methoxy-1,2,3,4-tetrahydronaphthalene
  参考文献：
  名称：

  [EN] TRITIUM RADIOLABELING OF [3H]-1-CYCLOHEXYL-4-[3-(5-METHOXY-1,2, 3,4,-TETRAHYDRONAPHTHALEN-1-YL)-N-PROPYL]PIPERAZINE ([3H]-PB28), AS A POTENT SIGMA-2 RECEPTOR LIGAND
  [FR] RADIOMARQUAGE AU TRITIUM DE [3H]-1-CYCLOHEXYL-4-[3-(5- MÉTHOXY-1,2,3,4-TÉTRAHYDRONAPHTALÈN-1-YL)-N-PROPYL]PIPÉRAZINE ([3H]-PB28), EN TANT QUE LIGAND EFFICACE DES RÉCEPTEURS SIGMA-2

  摘要：

  该发明涉及一种新型方法，用于对公式1中的l-环己基-4-[3-(5-甲氧基-1,2,3,4,-四氢萘基)-n-丙基]哌嗪（PB28）配体进行[3H]放射标记，以及其对映体形式，特异于sigma-2受体。该发明还涉及同一放射标记的配体及其用途，作为在组织中评估所述受体表达水平的高度选择性分析仪器，作为新型特异性配体的选择工具，并作为诊断试剂盒中的诊断试剂。

  公开号：

  WO2009104058A1

文献信息

• 4-(Tetralin-1-yl)- and 4-(Naphthalen-1-yl)alkyl Derivatives of 1-Cyclohexylpiperazine as σ Receptor Ligands with Agonist σ₂ Activity
  作者：Francesco Berardi、Savina Ferorelli、Carmen Abate、Nicola Antonio Colabufo、Marialessandra Contino、Roberto Perrone、Vincenzo Tortorella

  DOI：10.1021/jm031026e

  日期：2004.4.1

  Several 1-cyclohexylpiperazine derivatives related to sigma(2) receptor ligand 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (33, K(i) = 0.34 nM) were synthesized and tested in radioligand binding assays, to attempt a structure-affinity relationship study. Intermediate alkyl chain length and methoxyl group position on the tetralin nucleus were varied. A few naphthalene

  与sigma（2）受体配体1-cyclohexyl-4- [3-（5-甲氧基-1,2,3,4-四氢萘-1-基）丙基]哌嗪有关的几种1-cyclohexylpiperazine衍生物（33，K（i合成＝ 0.34nM）并在放射性配体结合测定中测试，以尝试结构亲和关系研究。中间烷基链长度和四氢化萘核上的甲氧基位置是变化的。还制备了一些萘类似物。在几乎所有化合物的sigma（2）受体结合物中都发现了高亲和力，其中一些化合物在亚纳摩尔范围内显示出K（i）值，但是发现了低sigma（2）/ sigma（1）选择性。具有三个（32和43）或五个亚甲基（39和46）的中间烷基链的化合物显示出最高的sigma（2）亲和力。发现具有四亚甲基链的化合物具有相当高的sigma（1）受体亲和力。36（K（i）= 0.036 nM）和45（K（i）= 0.22 nM）显示出良好的sigma（1）/ sigma（2）
• Novel Potent σ₁ Ligands:  <i>N</i>-[ω-(Tetralin-1-yl)alkyl]piperidine Derivatives
  作者：Francesco Berardi、Giuseppe Giudice、Roberto Perrone、Vincenzo Tortorella、Stefano Govoni、Laura Lucchi

  DOI：10.1021/jm9508898

  日期：1996.1.1

  N-[(tetralin-1-yl)alkyl]piperidines and a number of related N-di-n-propyl-[(tetralin-1-yl)alkyl]amines were prepared. Structural modifications such as piperidine substitutions, intermediate chain lengthening, and the nature of the aromatic ring were explored in order to identify structural requirements for selective sigma 1 affinity. They were tested in radioligand binding assays on sigma 1, 5-HT1A and 5-HT2

  制备了一系列取代的N-[（四氢-1-基）烷基]哌啶和许多相关的N-二-正丙基-[（四氢-1-基）烷基]胺。为了确定选择性sigma 1亲和力的结构要求，对诸如哌啶取代，中间链加长和芳环性质等结构修饰进行了研究。在放射性配体结合测定中对它们进行了测试，其中包括sigma 1、5-HT1A和5-HT2血清素能，PCP（苯环利定）和D-2多巴胺能受体。此处报道的几乎所有化合物均显示出高至超强的sigma 1亲和力，并且某些化合物还表现出比其他受体广泛的选择性。在[3H]-（+）-戊唑啉结合中，3,3-二甲基-1- [3-（5-甲氧基-1,2,3,4-四氢萘-1-基）-正丙基]哌啶（24 ）和3,3-二甲基-1- [4-（1,2,3，4-四氢萘-1-基）正丁基哌啶（26）达到最低的Ki值（分别为0.4和0.8 nM）。化合物24还表现出相当大的PCP亲和力（Ki = 34.2 nM），而化合物26
• Design and Evaluation of Naphthol- and Carbazole-Containing Fluorescent σ Ligands as Potential Probes for Receptor Binding Studies
  作者：Savina Ferorelli、Carmen Abate、Nicola Antonio Colabufo、Mauro Niso、Carmela Inglese、Francesco Berardi、Roberto Perrone

  DOI：10.1021/jm070373b

  日期：2007.9.1

  Some 3,3-dimethyl-1-(3-naphthylpropyl)piperidine and 1-cyclohexyl-4-(3-naphthylpropyl)piperazine derivatives, structurally containing naphthol as a fluorescent moiety, were prepared for being potentially used as fluorescent sigma ligands. Structurally related analogs were also prepared, where the naphthalene nucleus was replaced by the fluorescent carbazole moiety and chain length was varied. For all

  制备了一些结构上含有萘酚作为荧光部分的3，3-二甲基-1-（3-萘基丙基）哌啶和1-环己基-4-（3-萘基丙基）哌嗪衍生物，它们有可能被用作荧光σ配体。还制备了结构相关的类似物，其中萘核被荧光咔唑部分取代，并且链长变化。对于所有化合物，均测量了对sigma受体和Delta8-Delta7固醇异构酶位点的体外亲和力，并确定了荧光性质。化合物19的sigma受体亲和力（sigma1，Ki = 6.78 nM和sigma2，Ki = 26.4 nM）和荧光特征均给出了最佳结果。因此，它被选择用于sigma受体的体外饱和结合分析。
• 1-Substituted-4-[3-(1,2,3,4-tetrahydro-5- or 7-methoxynaphthalen-1-yl)propyl]piperazines: influence of the N -1 piperazine substituent on 5-HT 1A receptor affinity and selectivity versus D 2 and α 1 receptors. Part 6
  作者：Roberto Perrone、Francesco Berardi、Nicola A Colabufo、Marcello Leopoldo、Vincenzo Tortorella

  DOI：10.1016/s0968-0896(00)00028-6

  日期：2000.5

  piperazine in terms of 5-HT1A binding affinity. In fact, 1-cyclohexyl, 1-(3-benzisoxazolyl), 1-(benzothiazole-2-carbonyl), 1-(2-benzothiazolyl), 1-(2-quinolyl) substituted piperazines 21-30 displayed moderate or low 5-HT1A receptor affinity; on the contrary, 1-(3-benzisothiazolyl) and 1-(1-naphthalenyl) substituted piperazines 19, 20 and 32 displayed high 5-HT1A receptor affinity, the Ki values being in

  在本论文中，我们报告了1取代的4- [3-（5-或7-甲氧基-1,2,3,4-四氢萘）在5-HT1A，D2和alpha1受体上的合成和结合情况-1-基）丙基]哌嗪衍生物19-32和一些相关的杂烷基衍生物33-35。将获得的结果与先前报道的1-苯基，1-（2-甲氧基苯基），1-（2-吡啶基）类似物2-9的结果进行比较。结果指出，就5-HT1A结合亲和力而言，连接在哌嗪N-1位的基团的关键作用。实际上，1-环己基，1-（3-苯并恶唑基），1-（苯并噻唑-2-羰基），1-（2-苯并噻唑基），1-（2-喹啉基）取代的哌嗪21-30显示中等或低5 -HT1A受体亲和力；相反，1-（3-苯并噻唑基）和1-（1-萘基）取代的哌嗪19，20和32显示出高的5-HT1A受体亲和力，Ki值在亚纳摩尔范围内。此外，与参考化合物2-9相比，化合物19、20和32表现出比alpha1受体更好的选择性。
• Sigma-2 Receptor Agonists as Possible Antitumor Agents in Resistant Tumors: Hints for Collateral Sensitivity
  作者：Mauro Niso、Carmen Abate、Marialessandra Contino、Savina Ferorelli、Amalia Azzariti、Roberto Perrone、Nicola Antonio Colabufo、Francesco Berardi

  DOI：10.1002/cmdc.201300291

  日期：2013.12

  adenocarcinoma cells, with similar activity in the corresponding doxorubicin‐resistant MCF7adr cell line. Surprisingly, a few compounds, including 25, displayed enhanced activity in MCF7adr cells over parent cells, recalling the phenomenon of collateral sensitivity, which is under study for the treatment of drug‐resistant tumors. All of the compounds showed interaction with P‐glycoprotein (P‐gp), and 15

  与促进新的抗肿瘤剂的开发为目标，高亲和力σ 2受体激动剂被开发，用6,7-二甲氧基-2- [4- [1-（4-氟苯基）-1- ħ吲哚-3- [-基]丁基] -1,2,3,4-四氢异喹啉（15）和9- [4-（6,7-二甲氧基-1,2,3,4-四氢异喹啉-2-基）丁基] -9 H -咔唑（25）示出了特殊的选择性为σ 2亚型。大多数化合物在人MCF7乳腺腺癌细胞中显示出显着的抗增殖活性，在相应的对阿霉素耐药的MCF7adr细胞系中也具有相似的活性。令人惊讶的是，其中一些化合物包括25种，显示MCF7adr细胞的活性比亲代细胞增强，回想起附带敏感性的现象，该现象正在研究中，用于治疗耐药性肿瘤。所有这些化合物均显示与P-糖蛋白（P-gp）相互作用，而15和25具有最大的活性，能够逆转P-gp介导的耐药性，并重新建立阿霉素在MCF7adr细胞中的抗肿瘤作用。因此，我们确定了一系列σ的2赋有耐人寻味抗肿瘤特性受体激动剂;