(E)-1-(3-chloro-4-propylidene)-5-methoxy-1,2,3,4-tetrahydronaphthalene | 161923-60-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: (E)-1-(3-chloro-4-propylidene)-5-methoxy-1,2,3,4-tetrahydronaphthalene
• 英文别名: (E)-1-(3-chloropropylidene)-1,2,3,4-tetrahydro-5-methoxynaphthalene；1-(3-chloro-n-propylidene)-5-methoxy-1,2,3,4-tetrahydronaphthalene；(4E)-4-(3-chloropropylidene)-8-methoxy-2,3-dihydro-1H-naphthalene
• CAS: 161923-60-0
• 化学式: C₁₄H₁₇ClO
• 分子量: 236.741
• InChiKey: GNBAHEKJMVKPGS-IZZDOVSWSA-N

物化性质

• 沸点：
  378.6±37.0 °C(predicted)
• 密度：
  1.152±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  16
• 可旋转键数：
  3
• 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：

  (E)-1-(3-chloro-4-propylidene)-5-methoxy-1,2,3,4-tetrahydronaphthalene 、 2-苯氧基乙胺 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 以33%的产率得到(E)-3-(3,4-dihydro-5-methoxy-1(2H)-naphthalenylidene)-N-(2-phenoxyethyl)propanamine
  参考文献：
  名称：

  Perrone, Roberto; Berardi, Francesco; Colabufo, Nicola A., Medicinal Chemistry Research, 1999, vol. 9, # 5, p. 340 - 353

  摘要：

  DOI：
• 作为产物：
  描述：

  1-cyclopropyl-5-methoxy-1,2,3,4-tetrahydronaphthalen-1-ol 在 盐酸 作用下， 以 溶剂黄146 为溶剂， 生成 (E)-1-(3-chloro-4-propylidene)-5-methoxy-1,2,3,4-tetrahydronaphthalene
  参考文献：
  名称：

  对1-芳基-4- [1-四氢]烷基]哌嗪的5-HT1A受体具有高亲和力和选择性。2。

  摘要：

  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。

  DOI：

  10.1021/jm00006a013

文献信息

• Structure−Activity Relationship Studies on the 5-HT_1A Receptor Affinity of 1-Phenyl-4-[ω-(α- or β-tetralinyl)alkyl]piperazines. 4
  作者：Roberto Perrone、Francesco Berardi、Nicola A. Colabufo、Marcello Leopoldo、Vincenzo Tortorella、Maria Gioia Fornaretto、Carla Caccia、Robert A. McArthur

  DOI：10.1021/jm9604538

  日期：1996.1.1

  The synthesis of 1-phenylpiperazines, linked in the alpha or beta position of the tetralin moiety on the terminal part of the N-4 alkyl chain, and their radioligand binding affinities for 5-HT1A, 5-HT2A, D-1, D-2, alpha(1), and alpha(2) receptors along with SAR studies on the 5-HT1A receptor are reported. Several changes have been carried out on previous structures of type 2, by inserting the alkyl chain with variable length in the alpha or beta position of the tetralin moiety and by changing the position of the methoxy group on the aromatic ring of the tetralin nucleus. The highest affinity (IC50 = 0.50 nM) and selectivity for the 5-HT1A receptor were showed by 1-phenylpiperazine 2a with a three-membered alkyl chain bearing a 5-methoxytetralin-1-yl ring in the omega position.
• 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.
• [EN] VERAPAMIL ANALOGUES WITH INHIBITION ACTIVITY ON ABC (ATP BINDING CASSETTE) CELL EXTRUSION PUMPS<br/>[FR] Analogues du vérapamil ayant une activité d'inhibition des pompes d'extrusion cellulaire d'ABC (cassette de liaison à l'ATP)
  申请人：ISTITUTO TUMORI GIOVANNI PAOLO

  公开号：WO2008017588A1

  公开（公告）日：2008-02-14

  [EN] The invention relates to a new class of compounds able to inhibit in a dose-dependent manner Glycoprotein-P (P-gp) activity in cell lines in which the expression of said glycoprotein is very high, like Caco-2 (human colon cancer) cells and MCF7/Adr (adriamycin-resistant human breast carcinoma) cells. The invention also relates to the use of such compounds as medicaments useful in the treatment of states linked to the difficulty for some drugs to cross the blood-brain barrier (BBB) and generally within the context of the problems of drug resistance induced by chemotherapy agents.
  [FR] L'invention concerne une nouvelle classe de composés capables d'inhiber de manière dépendante de la dose l'activité de la glycoprotéine P (P-gp) dans des lignées cellulaires dans lesquelles l'expression de cette glycoprotéine est très élevée, par exemple les cellules Caco-2 (cancer du côlon humain) et les cellules MCF7/Adr (cancer du sein humain résistant à l'adriamycine). L'invention concerne également l'utilisation de ces composés en tant que médicaments utiles dans le traitement d'états liés à la difficulté qu'ont certaines substances médicamenteuses à franchir la barrière hémato-encéphalique (BHE) et en général dans le contexte des problèmes de la résistance aux médicaments induite par des agents chimiothérapeutiques.
• 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。
• Perrone, Roberto; Berardi, Francesco; Colabufo, Nicola A., Medicinal Chemistry Research, 1999, vol. 9, # 5, p. 340 - 353
  作者：Perrone, Roberto、Berardi, Francesco、Colabufo, Nicola A.、Leopoldo, Marcello、Tortorella, Vincenzo

  DOI：——

  日期：——