2-(Pyridin-4-yl)-methylene-indan-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: 2-(Pyridin-4-yl)-methylene-indan-1-one
• 英文别名: (Z)-2-(pyridin-4-ylmethylene)-2,3-dihydroinden-1-one；(2Z)-2-(pyridin-4-ylmethylidene)-3H-inden-1-one
• 化学式: C₁₅H₁₁NO
• 分子量: 221.258
• InChiKey: UFLITIQLRTXBDW-LCYFTJDESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  17
• 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：
  30
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  (E)-2-(pyridin-4-ylmethylene)-2,3-dihydro-1H-inden-1-one 以 乙醇 为溶剂， 反应 48.0h， 以22%的产率得到2-(Pyridin-4-yl)-methylene-indan-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

• Process for the preparation of benzyl-piperidylmethyl-indanones
  申请人：Bayer Aktiengesellschaft

  公开号：US05606064A1

  公开（公告）日：1997-02-25

  The invention relates to a new process for the preparation of benzyl-piperidylmethyl-indanones known as medicaments, which is characterized in that the appropriately substituted pyridinium salts are hydrogenated.

  这项发明涉及一种用于制备被称为药物的苄基-哌啶甲基-茚酮的新工艺，其特征在于适当取代的吡啶盐经过氢化。
• Stable lamotrigine pharmaceutical compositions and processes for their preparation
  申请人：Kumar Yatendra

  公开号：US20070129549A1

  公开（公告）日：2007-06-07

  The invention relates to processes for the preparation of piperidylmethyl-indanones, and to the use of these compounds as intermediates for the preparation of benzyl-piperidylmethyl-indanones which are active compounds for the treatment of CNS disorders. The invention also relates to a process for the preparation of donepezil or a pharmaceutically acceptable salt thereof, and pharmaceutical compositions that include the donepezil or a pharmaceutically acceptable salt thereof.

  本发明涉及制备哌啶基甲基-茚酮类化合物的方法，以及将这些化合物用作制备苯基-哌啶基甲基-茚酮类活性化合物（用于治疗中枢神经系统疾病）的中间体的用途。本发明还涉及制备多奈哌齐或其药学上可接受的盐的方法，以及包括多奈哌齐或其药学上可接受的盐的制药组合物。
• (1-Indanon-2yl)methylpiperidines, intermediates and a process for their preparation and their use as medicaments
  申请人：HOECHST-ROUSSEL PHARMACEUTICALS INCORPORATED

  公开号：EP0535496A1

  公开（公告）日：1993-04-07

  The present invention relates to (1indanon-2-yl)methylpiperidines of the formula wherein R is hydrogen, loweralkyl, or a group of the formula R₁ is hydrogen or a group of the formula W, X, and Y are hydrogen, loweralkyl, loweralkoxy, halogen, nitro, or trifluoromethyl; n is 1 or 2; the optical isomers thereof, or the pharmaceutically acceptable acid addition salts thereof, which are useful in relieving memory dysfunction, alone or in combination with inert adjuvants, and are thus indicated in the treatment of Alzheimer's disease.

  本发明涉及式中的(1-茚满-2-基)甲基哌啶 其中 R 是氢、低级烷基或式中的基团 R₁是氢或式中的基团 W、X 和 Y 是氢、低级烷基、低级烷氧基、卤素、硝基或三氟甲基；n 是 1 或 2；其光学异构体或其药学上可接受的酸加成盐，可单独或与惰性佐剂结合用于缓解记忆功能障碍，因此适用于治疗阿尔茨海默病。
• Verfahren zur Herstellung von Benzyl-piperidylmethylindanonen
  申请人：BAYER AG

  公开号：EP0711756A1

  公开（公告）日：1996-05-15

  Die Erfindung betrifft ein neues Verfahren zur Herstellung von als Arzneimittel bekannte Benzyl-piperidylmethyl-indanonen (I), das dadurch gekennzeichnet ist, daß man die entsprechend substituierten Pyridiniumsalze hydriert. in welcher R¹,R²,R³ und R⁴gleich oder verschieden sind und für Wasserstoff oder für geradkettiges oder verzweigtes Alkyl, Alkoxy oder Alkoxycarbonyl mit bis zu 6 Kohlenstoffatomen, für Alkyl- oder Dialkyl-(C₁-C₆)-aminocarbonyloxy oder Halogen steht.

  本发明涉及一种制备苄基-哌啶基甲基-茚酮 (I) 的新工艺，其特点是将相应取代的吡啶鎓盐进行氢化。 其中 R¹、R²、R³ 和 R⁴ 相同或不同，代表氢或 代表具有最多 6 个碳原子的直链或支链烷基、烷氧基或烷氧基羰基、烷基或二烷基-(C₁-C₆)-氨基羰氧基或卤素。
• US5606064A
  申请人：——

  公开号：US5606064A

  公开（公告）日：1997-02-25