(E)-4-hydroxy-2-(pyridin-4-ylmethylene)-2,3-dihydro-1H-inden-1-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: (E)-4-hydroxy-2-(pyridin-4-ylmethylene)-2,3-dihydro-1H-inden-1-one
• 英文别名: 4-Hydroxy-2-[1-pyridin-4-yl-meth-(E)-ylidene]-indan-1-one；(2E)-4-hydroxy-2-(pyridin-4-ylmethylidene)-3H-inden-1-one
• 化学式: C₁₅H₁₁NO₂
• 分子量: 237.258
• InChiKey: BQBDUNUCJDXMNP-DHZHZOJOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  50.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-4-hydroxy-2-(pyridin-4-ylmethylene)-2,3-dihydro-1H-inden-1-one 在 盐酸 作用下， 以 水 、 丙酮 为溶剂， 以77.1%的产率得到(E)-4-((4-hydroxy-1-oxo-1H-inden-2(3H)-ylidene)methyl)pyridin-1-ium chloride
  参考文献：
  名称：

  Synthesis and biological evaluation of pyridine-linked indanone derivatives: Potential agents for inflammatory bowel disease

  摘要：

  A series of pyridine-linked indanone derivatives were designed and synthesized to discover new small molecules for the treatment of inflammatory bowel disease (IBD). Compounds 5b and 5d exhibited strongest inhibitory activity against TNF-alpha-induced monocyte adhesion to colon epithelial cells (an in vitro model of colitis). In TNBS (2,4,6-trinitrobenzenesulfonic acid)-induced rat colitis model, oral administration of the compounds 5b and 5d ameliorated colitis with significant recovery in altered expressions of E-cadherin, TNF-alpha and IL-1 beta expressions, indicating 5b and 5d as potential agents for therapeutics development against IBD.

  DOI：

  10.1016/j.bmcl.2018.06.012
• 作为产物：
  描述：

  4-甲氧基-1-茚酮 在 哌啶 、 甲醇 、 三溴化硼 、 溶剂黄146 作用下， 反应 6.0h， 生成 (E)-4-hydroxy-2-(pyridin-4-ylmethylene)-2,3-dihydro-1H-inden-1-one
  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

文献信息

• 2–Benzylidene–1–Indanone Analogues as Dual Adenosine A1/A2a Receptor Antagonists for the Potential Treatment of Neurological Conditions
  作者：HelenaDorathea Janse van Rensburg、LesetjaJ. Legoabe、Gisella Terre’Blanche、MiethaM. Van der Walt

  DOI：10.1055/a-0808-3993

  日期：2019.7

  of ring B with chlorine lead to the highly potent and selective adenosine A2A receptor antagonist, compound 2 H: . Compound 2C: and the 2Q: behaved as adenosine A1 receptor antagonists in the performed GTP shift assays. In view of these findings, compounds 2C: , 2 H: , 2Q: and 2P: are potent and selective adenosine A1 and A2A receptor antagonists for the potential treatment of neurological conditions

  先前的研究探索了2-苄基-1-四氢萘酮衍生物作为创新的腺苷A1和A2A受体拮抗剂，用于帕金森氏病的替代性非多巴胺能治疗。这项研究的目的是研究与结构相关的2-亚苄基-1-茚满酮，在环A和B上进行取代，作为新型，有效和选择性的腺苷A1和A2A受体阻滞剂。通过酸催化的醛醇缩合反应合成2-苄叉基-1-茚满酮衍生物，并通过放射性配体结合测定法进行评估，以确定结构活性关系来控制A1和A2A AR亲和力。结果表明，与在C5（2D）处的取代相比，在2-亚苄基-1-茚满酮骨架（2C :)的A环C4处的羟基取代和B环的间（3'）或对位（4'）取代：）或C6（2E：环A）在微摩尔范围内对腺苷A1受体的活性和选择性。此外，在环B的间位（3'）处用氯取代导致高效且选择性强的腺苷A2A受体拮抗剂化合物2 H：。在执行的GTP位移分析中，化合物2C：和2Q：充当腺苷A1受体拮抗剂。鉴于这些发现，化合物2C：，2 H：，
• Synthesis and biological evaluation of pyridine-linked indanone derivatives: Potential agents for inflammatory bowel disease
  作者：Tara Man Kadayat、Suhrid Banskota、Ganesh Bist、Pallavi Gurung、Til Bahadur Thapa Magar、Aarajana Shrestha、Jung-Ae Kim、Eung-Seok Lee

  DOI：10.1016/j.bmcl.2018.06.012

  日期：2018.8

  A series of pyridine-linked indanone derivatives were designed and synthesized to discover new small molecules for the treatment of inflammatory bowel disease (IBD). Compounds 5b and 5d exhibited strongest inhibitory activity against TNF-alpha-induced monocyte adhesion to colon epithelial cells (an in vitro model of colitis). In TNBS (2,4,6-trinitrobenzenesulfonic acid)-induced rat colitis model, oral administration of the compounds 5b and 5d ameliorated colitis with significant recovery in altered expressions of E-cadherin, TNF-alpha and IL-1 beta expressions, indicating 5b and 5d as potential agents for therapeutics development against IBD.
• Aromatase Inhibitors. Syntheses and Structure-Activity Studies of Novel Pyridyl-Substituted Indanones, Indans, and Tetralins
  作者：Rolf W. Hartmann、Herbert Bayer、Gertrud Gruen

  DOI：10.1021/jm00035a007

  日期：1994.4

  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.