7-Hydroxy-2-pyridin-4-ylmethylene-3,4-dihydro-2H-naphthalen-1-one | 135075-28-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 7-Hydroxy-2-pyridin-4-ylmethylene-3,4-dihydro-2H-naphthalen-1-one
• 英文别名: (2E)-7-hydroxy-2-(pyridin-4-ylmethylidene)-3,4-dihydronaphthalen-1-one
• CAS: 135075-28-4
• 化学式: C₁₆H₁₃NO₂
• 分子量: 251.285
• InChiKey: AAARKAYZOWLPBX-UKTHLTGXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  50.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  7-甲氧基-1-萘满酮 在 哌啶 、 三溴化硼 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 生成 7-Hydroxy-2-pyridin-4-ylmethylene-3,4-dihydro-2H-naphthalen-1-one
  参考文献：
  名称：

  New aromatase inhibitors. Synthesis and biological activity of pyridyl-substituted tetralone derivatives

  摘要：

  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.

  DOI：

  10.1021/jm00113a004

文献信息

• Potent inhibitory activity of hydroxylated 2-benzylidene-3,4-dihydronaphthalen-1(2H)-ones on LPS-stimulated reactive oxygen species production in RAW 264.7 macrophages
  作者：Surendra Kunwar、Su Min Lee、Tara Man Kadayat、Aarajana Shrestha、Pil-Hoon Park、Eung-Seok Lee

  DOI：10.1016/j.bmcl.2022.128921

  日期：2022.10

  This study attempted to discover tetralone-derived potent ROS inhibitors by synthesizing sixty-six hydroxylated and halogenated 2-benzylidene-3,4-dihydronaphthalen-1(2H)-ones via Claisen-Schmidt condensation reaction. The majority of the synthesized and investigated compounds significantly inhibited ROS in LPS-stimulated RAW 264.7 macrophages. When compared to malvidin (IC50 = 9.00 µM), compound 28

  本研究试图通过 Claisen-Schmidt缩合反应合成 66 个羟基化和卤化的 2-亚苄基-3,4-二氢萘-1(2 H )-酮来发现四氢萘酮衍生的强效 ROS 抑制剂。大多数合成和研究的化合物显着抑制 LPS 刺激的 RAW 264.7 巨噬细胞中的 ROS。与锦葵素 (IC 50 = 9.00 µM) 相比，具有 6-羟基和 2-三氟甲基苯基部分的化合物28 (IC 50 = 0.18 µM) 显示出最有效的 ROS 抑制作用。此外，化合物20、31、39、45、47- _ _ _ _ _ _ _与参考化合物相比，图48、52、55-56、58-60和62也显示出高十倍的ROS抑制活性。基于构效关系研究，在四氢萘酮支架的 6 位和 7 位结合羟基以及苯环 B 中的不同卤素官能团对于有效的 ROS 抑制至关重要。本研究有助于更好地了解卤素和酚基在 ROS 抑制中的作用，对 2-benzylidene-3
• 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.