2-(4-Pyridylmethyl)-1-tetralon | 14711-41-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 2-(4-Pyridylmethyl)-1-tetralon
• 英文别名: 2-(γ-Pyridylmethyl)-1-tetralon；2-pyridin-4-ylmethyl-3,4-dihydro-2H-naphthalen-1-one；2-(Pyridin-4-ylmethyl)-3,4-dihydronaphthalen-1(2H)-one；2-(pyridin-4-ylmethyl)-3,4-dihydro-2H-naphthalen-1-one
• CAS: 14711-41-2
• 化学式: C₁₆H₁₅NO
• mdl: MFCD00033038
• 分子量: 237.301
• InChiKey: LQEDVMDTNOBJHU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  30
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(4-Pyridylmethyl)-1-tetralon 在 氢氧化钾 、 一水合肼 作用下， 生成 4-(1,2,3,4-Tetrahydro-naphthalen-2-ylmethyl)-pyridine
  参考文献：
  名称：

  Aromatase Inhibitors. Syntheses and Structure-Activity Studies of Novel Pyridyl-Substituted Indanones, Indans, and Tetralins

  摘要：

  The (E)-2-(4-pyridylmethylene)-1-indanones (E)-1-(E)-5[(E)-1, H; (E);2, 4-OCH3; (E)-3, 5-OCH3; (E)-4, 4-OH; (E)-5,5-OH] were obtained by aldol condensation of the corresponding 1-indanones with 4-pyridinecarboxaldehyde, and in case of the OH compound (E)-4 subsequent ether cleavage of (E)-2. The synthesis of the (Z)-isomers (Z)-1-(Z)-3 [(Z)-1, H; (Z)-2, 4-OCH3; (Z)-3, 5-OCH3] was accomplished by UV irradiation of the corresponding (E)-isomers. Catalytic hydrogenation of (E)-1-(E)-3 gave the 2-(4-pyridylmethyl)-1-indanones 6-8 (6, H; 7, 4-OCH3; 8, 5-OCH3). The 2-(4-pyridylmethyl)-substituted indans 11-13 (11, H; 12, 4-OCH3; 13, 5-OCH3) and the tetralins 16-19 (16, H; 17, 5-OCH3; 18, 6-OCH3; 19, 7-OCH3) were obtained by reduction of the corresponding ketones using N2H4/KOH. The 2-(4-pyridylmethyl)-substituted indanones 9 (4-OH) and 10 (5-OH), indans 14 (4-OH) and 15 (5-OH), and tetralins 20-22 (20, 5-OH; 21, 6-OH; 22, 7-OH) were synthesized by ether cleavage of the corresponding OCH3 compounds. All compounds showed inhibition of human placental aromatase exhibiting relative potencies from 0.9 [(E)-4] to 163 [18; aminoglutethimide (AC) potency E 1]. Compounds 13 and 18 showed competitive type of inhibition and a type II difference spectrum, indicating the interaction of the pyridyl-N with the central Fe(III) ion of the cytochrome P450 heme component. Only the OH-substituted indans and tetralins inhibited bovine adrenal desmolase with maximum activity shown by 20 and 22 (12% inhibition, 25 mu M; AG, 53 % inhibition, 25 mu M). In vivo, however, all tested aromatase inhibitors (6, 8, 10, 14, 15, 18 and 20) were less active than AG concerning the inhibition of the uterotrophic activity of androstenedione (6, 8, 10, 15), the reduction of the plasma estradiol concentration (14, 20), and the mammary carcinoma (MC) inhibiting properties (18, 20; androstenedione-stimulated juvenile rats, pregnant mares' serum gonadotropin-primed rats as well as dimethylbenzanthracene-induced MC of the Sprague-Dawley rat, postmenopausal experiment). Since no affinity to the estrogen receptor was demonstrated (20), estrogenic effects as a cause for the poor tumor inhibiting activity have to be excluded.

  DOI：

  10.1021/jm00035a007
• 作为产物：
  描述：

  (E)-2-(pyridine-4-ylmethylene)-3,4-dihydronaphthalen-1-(2H)-one 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 以86%的产率得到2-(4-Pyridylmethyl)-1-tetralon
  参考文献：
  名称：

  吡啶基取代的四氢呋喃衍生物：一类新的非甾体芳香酶抑制剂

  摘要：

  以黄酮和黄烷酮这两种具有弱芳香化酶抑制作用的天然产物为原料，合成了化合物1-7，并研究了它们对芳香化酶和解链酶的抑制活性。除化合物 2 外，所有衍生物均显示出比起始化合物更强的芳香化酶抑制作用，并且证明是比市场上唯一的活性成分氨基鲁米特 (AG) 更有效的芳香化酶抑制剂。与 AG 相比，化合物 1 和 3-7 没有显示出对解糖酶的抑制，这会导致 AG 出现不良副作用。

  DOI：

  10.1002/ardp.2503241008

文献信息

• Metal-Free Synthesis of C-4 Substituted Pyridine Derivatives Using Pyridine-boryl Radicals via a Radical Addition/Coupling Mechanism: A Combined Computational and Experimental Study
  作者：Guoqiang Wang、Jia Cao、Liuzhou Gao、Wenxin Chen、Wenhao Huang、Xu Cheng、Shuhua Li

  DOI：10.1021/jacs.7b00823

  日期：2017.3.15

  that the pyridine-boryl radical generated in situ using 4-cyanopyridine and bis(pinacolato)diboron could be used as a bifunctional "reagent", which serves as not only a pyridine precursor but also a boryl radical. With the unique reactivity of such radicals, 4-substituted pyridine derivatives could be synthesized using α,β-unsaturated ketones and 4-cyanopyridine via a novel radical addition/C-C coupling

  密度泛函理论研究表明，使用 4-氰基吡啶和双（频哪醇）二硼原位生成的吡啶-硼基自由基可用作双功能“试剂”，其不仅可用作吡啶前体，还可用作硼基自由基。由于这些自由基的独特反应性，可以使用α,β-不饱和酮和4-氰基吡啶通过新型自由基加成/CC偶联机制合成4-取代吡啶衍生物。进行了几个对照实验，为所提出的机制提供支持性证据。除了烯酮，范围还可以扩展到广泛的硼基自由基受体，包括各种醛和酮、芳基亚胺和炔酮。最后，这种转化应用于复杂药物分子的后期修饰。
• Novel Series of Imidazolyl Substituted Steroidal and Indan-1-One Derivatives
  申请人：Bansal Ranju

  公开号：US20090137541A1

  公开（公告）日：2009-05-28

  The present invention provides a novel series of imidazolyl substituted steroidal and indan-1-one derivatives and salts thereof having the following general structural formulae (A and B)

  本发明提供了一种新的咪唑基取代类固醇和茚环-1-酮衍生物及其盐，其具有以下一般结构式（A和B）。
• A Comparative Study of the Enantiomeric Resolution of Several Tetralone Derivatives on Macrocyclic Antibiotic Chiral Stationary Phases Using HPLC under Normal Phase Mode
  作者：Hassan Y. Aboul-Enein、Imran Ali

  DOI：10.1002/1521-4184(200107)334:7<258::aid-ardp258>3.0.co;2-g

  日期：2001.7

  The enantiomeric resolution of five substituted 2‐(4‐pyridylalkyl)‐1‐ tetralone derivatives has been achieved on three macrocyclic glycopeptide antibiotic chiral stationary phases namely, Chiro‐biotic R, T, and V columns. The mobile phase used was hexane‐ethanol‐ triethylamine (12:8:0.01, v/v/v). The flow rates were 1 mL/min for Chirobiotic T and 2 mL/min for Chirobiotic R and V respectively. The UV

  五种取代的 2-(4-吡啶基烷基)-1-四氢萘酮衍生物的对映体拆分已在三种大环糖肽抗生素手性固定相即 Chiro-biotic R、T 和 V 色谱柱上实现。使用的流动相是己烷-乙醇-三乙胺（12:8:0.01，v/v/v）。Chirobiotic T 的流速分别为 1 mL/min，Chirobiotic R 和 V 的流速分别为 2 mL/min。UV检测在254nm处进行，所报道的四氢萘酮衍生物的解析对映异构体的a值在Chirobiotic R上为1.32至2.51，在Chirobiotic T上为2.02至2.88，在Chirobiotic V上为1.55至2.54 Rs 的值分别在 Chirobiotic R 的 1.00 至 2.50 范围内，Chirobiotic T 的 1.00 至 1.95 和 Chirobiotic V 的 1.00 至 1.60。
• New aromatase inhibitors. Synthesis and biological activity of pyridyl-substituted tetralone derivatives
  作者：Herbert Bayer、Christine Batzl、Rolf W. Hartman、Albrecht Mannschreck

  DOI：10.1021/jm00113a004

  日期：1991.9

  The (E)-2-(4-pyridylmethylene)-1-tetralones 1-7 (1, H; 2, 5-OCH3; 3, 6-OCH3; 4, 7-OCH3; 5, 5-OH; 6, 6-OH; 7, 7-OH) were obtained by aldol condensation of the corresponding 1-tetralones with 4-pyridinecarboxaldehyde, and in the case of the OH compounds 5 and 7 subsequent ether cleavage of the OCH3-substituted 2-(4-pyridylmethylene)-1-tetralones. Catalytic hydrogenation of 1-4 gave the 2-(4-pyridylmethyl)-1-tetralones 8-11 (8, H; 9, 5-OCH3; 10, 6-OCH3; 11, 7-OCH3). Subsequent ether cleavage of 9-11 led to the corresponding OH compounds 12-14 (12, 5-OH; 13, 6-OH; 14, 7-OH). The enantiomers of 11 and 12 were separated semipreparatively by HPLC on triacetylcellulose. All compounds (1-14) showed an inhibition of human placental aromatase exhibiting relative potencies from 2.2 to 213 [compounds 6 and (+)-12, respectively; aromatase inhibitory potency of aminoglutethimide (AG) = 1]. The compounds exhibited no or only a weak inhibition of desmolase [cholesterol side chain cleavage enzyme; maximum activity shown by 12, 23 % inhibition (25-mu-M); AG, 53 % inhibition (25-mu-M)]. In vivo, however, the compounds were not superior to AG as far as the reduction of the plasma estradiol concentration and the mammary carcinoma (MC) inhibiting properties are concerned (PMSG-primed SD rats as well as DMBA-induced MC of the SD rat, pre- and postmenopausal experiments, and the transplantable MXT-MC of the BD2F1 mouse). This is due to a fast decrease of the plasma E2 concentration inhibiting effect as could be shown by a kinetic experiment. In addition, select compounds inhibited rat ovarian aromatase much less than human placental aromatase (12, factor of 10). Estrogenic effects as a cause for the poor in vivo activity of the test compounds could be excluded, since they did not show affinity for the estrogen receptor.
• US8361996B2
  申请人：——

  公开号：US8361996B2

  公开（公告）日：2013-01-29