4-(3-溴-n-丙基)-1,2-二氢-8-甲氧基萘 | 153526-80-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: 4-(3-溴-n-丙基)-1,2-二氢-8-甲氧基萘
• 英文名称: 4-(3-bromo-n-propyl)-1,2-dihydro-8-methoxynaphthalene
• 英文别名: 1-(3-bromopropyl)-5-methoxy-3,4-dihydronaphthalene；4-(3-Bromopropyl)-8-methoxy-1,2-dihydronaphthalene
• CAS: 153526-80-8
• 化学式: C₁₄H₁₇BrO
• 分子量: 281.192
• InChiKey: XYIRJLSKXYPFFS-UHFFFAOYSA-N

物化性质

• 沸点：
  369.9±42.0 °C(Predicted)
• 密度：
  1.285±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 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：

  4-(3-溴-n-丙基)-1,2-二氢-8-甲氧基萘 在 palladium on activated charcoal 盐酸 、 氢气 、 sodium carbonate 作用下， 以 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 2.0h， 生成 1-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-n-propyl]piperazine
  参考文献：
  名称：

  New σ and 5-HT_1A Receptor Ligands:  ω-(Tetralin-1-yl)-n-alkylamine Derivatives

  摘要：

  Two series of compounds that are structurally related to benzomorphans, derived by structural modification of arylpiperazines with high 5-HT1A affinity and moderate a affinity, were prepared in order to increase a affinity and selectivity. All new compounds are N-substituted-omega-(1,2,3,4-tetrahydronaphthalen-1-yl)- or -omega-(1,2-dihydronaphthalen-4-yl)-n-alkylamines with, in some cases, a methoxy group on the tetralin moiety. They were tested in radioligand binding assays on sigma ([H-3]DTG and [H-3]-(+)-pentazocine), D-2 dopaminergic, 5-HT1A and 5-HT2 serotonergic, and PCP (phencyclidine) receptors. A first set of compounds bearing a 4-(1-substituted)piperazine moiety as terminal fragment on the alkyl chain showed moderate to high sigma affinity (K-i = 5.3-139 nM), the most active and selective being 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-n-proyl]piperazine (14), with probable pronounced alpha(2) affinity (K-i = 5.3 nM on [H-3]DTG and K-i = 71 nM on [H-3]-(+)-pentazocine). Moreover, compound 13, a 1-benzylpiperazine analogue of 14, preserved a dual high 5-HT1A and sigma affinity (K-i = 3.6 nM on [H-3]-5-HT and K-i = 7.0 nM on [H-3]DTG). The second set of compounds includes some N-phenylalkyl derivatives of 3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-n-propylamine that can be considered. to be open-chain derivatives of 4-substituted-1-arylpiperazines. Among these compounds that had a lower activity toward sigma binding sites, a high 5-HT1A affinity was found for the N-(3-phenylpropyl) derivative 21 (K-i = 4.4 nM) which demonstrated very good selectivity.

  DOI：

  10.1021/jm950409c
• 作为产物：
  描述：

  5-甲氧基-3,4-二氢-2H-1-萘酮 在 potassium tert-butylate 、 氢溴酸 、 溶剂黄146 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 8.5h， 生成 4-(3-溴-n-丙基)-1,2-二氢-8-甲氧基萘
  参考文献：
  名称：

  DIHYDRONAPHTHALENE DERIVATIVE COMPOUNDS AND DRUGS CONTAINING THESE COMPOUNDS AS THE ACTIVE INGREDIENT

  摘要：

  公开号：

  EP1354879B1

文献信息

• Mixed 5-HT1A/D-2 activity of a new model of arylpiperazines: 1-aryl-4-[3-(1,2-dihydronaphthalen-4-yl)-n-propyl]piperazines. 1. Synthesis and structure-activity relationships
  作者：Roberto Perrone、Francesco Berardi、Nicola A. Colabufo、Vincenzo Tortorella、Francesco Fiorentini、Vincenzo Olgiati、Ermes Vanotti、Stefano Govoni

  DOI：10.1021/jm00027a012

  日期：1994.1

  and dopaminergic activity and to pursue the recent alternative approaches to the discovery of novel antipsychotic and anxiolytic agents. Title compounds were evaluated for in vitro activity on dopamine D-2 and serotonin 5-HT1A and 5-HT2 receptors by radioreceptor binding assays. They show high nanomolar affinity for 5-HT1A, moderate affinity for D-2, and low affinity for 5-HT2 receptors, and in particular

  合成了在烷基链上包含末端二氢萘片段的4-烷基-1-芳基哌嗪的新模型，以具有混合的血清素能和多巴胺能活性，并寻求发现新型抗精神病药和抗焦虑药的最新方法。通过放射受体结合测定法评价标题化合物对多巴胺D-2和5-羟色胺5-HT1A和5-HT2受体的体外活性。它们显示出对5-HT1A的高纳摩尔亲和力，对D-2的中等亲和力，对5-HT2受体的低亲和力，尤其是两种化合物4- [3-（1,2-二氢-6-甲氧基萘-4 -基）-正丙基] -1-（2-甲氧基苯基）哌嗪（8）和4- [3-（1,2-二氢-8-甲氧基萘-4-基）-正丙基] -1-（ 2-吡啶基）哌嗪（15），显示5-HT1A的IC50 = 2.0和1.4的值（nM），D-2的IC50 = 90.6和119.3的值（nM），分别。一些体内行为研究表明化合物8是5-HT1A受体的拮抗剂。这些最初的发现使新的芳基哌嗪与阿扎斯匹隆类化合物处于同一水平，例如1-（2-甲氧基苯基）-4-
• High Affinity and Selectivity on 5-HT1A Receptor of 1-Aryl-4-[(1-tetralin)alkyl]piperazines. 2
  作者：Roberto Perrone、Francesco Berardi、Nicola A. Colabufo、Marcello Leopoldo、Vincenzo Tortorella、Francesco Fiorentini、Vincenzo Olgiati、Alberto Ghiglieri、Stefano Govoni

  DOI：10.1021/jm00006a013

  日期：1995.3

  in order to increase the selectivity on the 5-HT1A versus D-2, alpha 1, sigma, and other 5-HT receptors. Many changes have been effected on previous structures of type 3(1-aryl-4-[3-(1,2-dihydronaphthalen-4-yl)-n-propyl]piperazines). Several synthetic procedures were followed to obtain the final products, depending on the presence or absence of a double bond, as well as of a heteroatom on the side chain

  为了增加5-HT1A对D-2，α1，σ和其他5-HT受体的选择性，合成了几种在侧链末端具有四氢萘部分的4-烷基-1-芳基哌嗪。许多变化已影响先前的类型3（1-芳基-4- [3-（1,2-二氢萘-4-基）-正丙基]哌嗪的结构。遵循几种合成程序以获得最终产物，这取决于双键以及侧链上杂原子的存在与否。在第一种情况下，可以广泛使用格利雅（Grignard）反应，而在第二种情况下，可以采用常规的合成方法。通过放射受体结合试验评估最终化合物对多巴胺D-1和D-2、5-羟色胺5-HT1A，5-HT1B，5-HT1C和5-HT2，α1肾上腺素和sigma受体的体外活性。
• Dihydronaphthalene derivative compounds and drugs containing these compounds as the active ingredient
  申请人：——

  公开号：US20040138213A1

  公开（公告）日：2004-07-15

  A compound of formula (I) 1 (wherein all symbols are as defined in the specification) and salt thereof, and peroxisome proliferator activated receptor regulator comprising thereof as active ingredient. Because a compound of formula (I) have an activity of regulating peroxisome proliferator activated receptor regulator, the compound of formula (I) is useful as a hypoglycemic agent, a hypolipidemic agent, a preventive and/or treatment agent for diseases associating metabolic disorders (diabetes, obesity, syndrome X, hypercholesterolemia, hyperlipoproteinemia, etc.), hyperlipemia, atherosclerosis, hypertension, circulatory diseases, overeating, coronary heart diseases, etc., an HDL cholesterol-elevating agent, an LDL cholesterol and/or VLDL cholesterol-lowering agent and a drug for relief from risk factors of diabetes or syndrome X.

  化合物式为（I）1（其中所有符号如规范所定义）及其盐，以及包含其作为活性成分的过氧化物酶增殖物激活受体调节剂。由于化合物（I）具有调节过氧化物酶增殖物激活受体调节剂的活性，因此化合物（I）可用作降糖剂、降脂剂、预防和/或治疗代谢紊乱相关疾病（糖尿病、肥胖症、X综合征、高胆固醇血症、高脂蛋白血症等）、高脂血症、动脉粥样硬化、高血压、循环系统疾病、暴饮暴食、冠心病等，是一种升高HDL胆固醇的药物，降低LDL胆固醇和/或VLDL胆固醇的药物，并可缓解糖尿病或X综合征的风险因素。
• Dihydronaphthalene derivative compounds and agent comprising the derivative as active ingredient
  申请人：Tajima Hisao

  公开号：US20060287304A1

  公开（公告）日：2006-12-21

  A compound of formula (I) (wherein all symbols are as defined in the specification) and salt thereof, and peroxisome proliferator activated receptor regulator comprising thereof as active ingredient. Because a compound of formula (I) have an activity of regulating peroxisome proliferator activated receptor regulator, the compound of formula (I) is useful as a hypoglycemic agent, a hypolipidemic agent, a preventive and/or treatment agent for diseases associating metabolic disorders (diabetes, obesity, syndrome X, hypercholesterolemia, hyperlipoproteinemia, etc.), hyperlipemia, atherosclerosis, hypertension, circulatory diseases, overeating, coronary heart diseases, etc., an HDL cholesterol-elevating agent, an LDL cholesterol and/or VLDL cholesterol-lowering agent and a drug for relief from risk factors of diabetes or syndrome X.

  化合物公式（I）（其中所有符号如规范中定义）及其盐，以及包含其作为活性成分的过氧化物酶增殖物激活受体调节剂。由于化合物公式（I）具有调节过氧化物酶增殖物激活受体调节剂的活性，因此化合物公式（I）可用作降血糖剂、降血脂剂、预防和/或治疗代谢紊乱疾病（糖尿病、肥胖症、X综合征、高胆固醇血症、高脂蛋白血症等）、高脂血症、动脉硬化、高血压、循环系统疾病、暴饮暴食、冠心病等，以及升高高密度脂蛋白胆固醇的药物、降低低密度脂蛋白和/或极低密度脂蛋白胆固醇的药物以及缓解糖尿病或X综合征风险因素的药物。
• Small P-gp modulating molecules: SAR studies on tetrahydroisoquinoline derivatives
  作者：Nicola Antonio Colabufo、Francesco Berardi、Mariangela Cantore、Maria Grazia Perrone、Marialessandra Contino、Carmela Inglese、Mauro Niso、Roberto Perrone、Amalia Azzariti、Grazia Maria Simone、Letizia Porcelli、Angelo Paradiso

  DOI：10.1016/j.bmc.2007.09.039

  日期：2008.1

  The development of small molecules as P-gp modulating agents and SAR studies on these ligands represented the aim of the present work. A series of 6,7-dimethoxytetrahydroisoquinoline derivatives was prepared and their ability to inhibit P-gp activity has been evaluated. The basic nucleus of these compounds, common to the best P-gp inhibitors such as Tariquidar and Elacridar, has been functionalized with no-basic moiety from our studied sigma receptor ligands displaying potent P-gp inhibition. The best results were obtained for compounds 3c and 3a (EC50 = 1.64 and 4.86 mu M, respectively) and these results were remarkable because Elacridar showed in the same biological evaluation similar inhibitory activity (EC50 = 2 mu M). SAR studies displayed that the removal of double bond on the spacer or its shifting into tetraline ring decreased the P-gp inhibiting activity. Moreover, the P-gp inhibition mechanism of tested compounds was investigated by three selected biological experiments. The results displayed that only compound 3c was P-gp inhibitor as Elacridar, while compound 3a and reference compounds Cyclosporin A and Verapamil modulated P-gp activity saturating the efflux pump as substrates. Flow cytometry studies carried out in Doxorubicin resistant breast cancer cell line (MCF7/Adr) confirmed that compound 3c increased Doxorubicin cell accumulation 5.7-fold. In addition, in MCF7/ Adr, antiproliferative effect of 5 mu M Doxorubicin shifted from 5% to 95% when co-administered with compound 3c (20 mu M). The present study suggested a new class of small molecules displaying P-gp inhibitor activity differing from reference compounds Elacridar and Tariquidar for a simplified, and in the meantime, efficacious no-basic moiety. (c) 2007 Elsevier Ltd. All rights reserved.