2--indanon-(1) | 4803-61-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 2--indanon-(1)
• 英文别名: 2-pyridin-4-ylmethyl-indan-1-one；2-[(4-pyridyl)methyl]-2,3-dihydro-1-1H-indenone；2-[(pyridin-4-yl)methyl]-2,3-dihydro-1-1H-indenone；2-(pyridin-4-ylmethyl)-2,3-dihydroinden-1-one
• CAS: 4803-61-6
• 化学式: C₁₅H₁₃NO
• 分子量: 223.274
• InChiKey: SQGMRMOPTFCLKQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 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--indanon-(1) 在 氢氧化钾 、 一水合肼 作用下， 生成 4-Indan-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-(pyridin-4-ylmethylene)-2,3-dihydro-1H-inden-1-one 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 以68%的产率得到2--indanon-(1)
  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

• [EN] OXIDISABLE PYRIDINE DERIVATIVES, THEIR PREPARATION AND USE AS ANTI-ALZHEIMER AGENTS<br/>[FR] DÉRIVÉS DE PYRIDINE OXYDABLE, LEUR PRÉPARATION ET LEUR UTILISATION EN TANT QU'AGENTS ANTI ALZHEIMER
  申请人：INSA INST NAT DES SCIENCES APPLIQUÉES DE ROUEN

  公开号：WO2014114742A1

  公开（公告）日：2014-07-31

  A compound of formula (I) in which the dotted lines indicate the presence of at least one double bond; n = 0 to 4; R3 and R4 are H, or when n = 1, R3 and R4 can also form together a double bond between the carbon atoms, and m = 0, 1 or 2, Z is CH or N or Z is C and - CHR3- is =CH- linked by the double bond to cyclopentanone; or - (-)m- is absent, and Z is NH, >N-alkyl, >N-phenyl, >N-benzyl or >N heteroaryl; R8 is alkyl, aryl or heteroaryl which can be optionally substituted; EWG represents an electron withdrawing group selected from the group comprising COOR, COSR, CONRR', CN, COR, CF3, SOR, SO2R, SONRR', SO2NRR', NO2, halogen, heteroaryl; and the pharmaceutical salts and stereisomers thereof. The compounds of formula (I) are potent in the treatment of neurodegenerative diseases such as Alzheimer's disease.

  式（I）的化合物，其中虚线表示至少存在一条双键；n = 0至4；R3和R4为H，或当n = 1时，R3和R4也可以共同形成碳原子之间的双键，m = 0、1或2，Z为CH或N，或Z为C且-CHR3-为=CH-通过双键连接到环戊酮；或-（-）m-不存在，Z为NH，>N-烷基，>N-苯基，>N-苄基或> N杂环烷基；R8为烷基、芳基或杂环烷基，可以选择性地被取代；EWG代表从包括COOR、COSR、CONRR'、CN、COR、CF3、SOR、SO2R、SONRR'、SO2NRR'、NO2、卤素、杂环烷基在内的电子吸引基团；以及其药用盐和立体异构体。式（I）的化合物在治疗诸如阿尔茨海默病等神经退行性疾病方面具有很强的作用。
• Process for the preparation of donepezil
  申请人：CHEMAGIS LTD

  公开号：US20040048893A1

  公开（公告）日：2004-03-11

  The invention provides a process for the preparation of a compound of the formula 6 comprising the hydrolysis and decarboxylation of a compound of the formula 5 according to the reaction: 1 wherein R and R 2 independently a C 1 -C 4 alkyl group or an aralkyl group.

  该发明提供了一种配方6的化合物制备过程，包括根据反应：1对配方5的化合物进行水解和脱羧，其中R和R2分别是C1-C4烷基或芳基烷基。
• Oxidisable pyridine derivatives, their preparation and use as anti-Alzheimer agents
  申请人：INSA (Institut National des Sciences Appliquees) de Rouen

  公开号：EP2759536A1

  公开（公告）日：2014-07-30

  A compound of the formula (I) in which the dotted lines indicate the presence of at least one double bond; n = 0 to 4; R3 and R4 are H, or when n = 1, R3 and R4 can also form together a double bond between the carbon atoms, and m = 0, 1 or 2, Z is CH or N or Z is C and -CHR3- is =CH- linked by the double bond to the cyclopentanone; or -(-)m- is absent, and Z is NH, >N-alkyl, >N-phenyl, >N-benzyl or >N-heteroaryl; R8 is alkyl, aryl or heteroaryl which can be optionally substituted; EWG represents an electron withdrawing group selected from the group comprising COOR, COSR, CONRR', CN, COR, CF3, SOR, SO2R, SONRR', SO2NRR', NO2, halogen, heteroaryl; and the pharmaceutical salts or tautomers thereof. The compounds of formula (I) are potent in the treatment of neurodegenerative diseases such as Alzheimer's disease.

  式(I)的化合物，其中虚线表示至少存在一个双键；n = 0到4；R3和R4为H，或当n = 1时，R3和R4也可以一起形成碳原子之间的双键，m = 0、1或2，Z为CH或N，或Z为C且-CHR3-为=CH-，通过双键与环戊酮相连；或-(-)m-不存在，Z为NH，>N-烷基，>N-苯基，>N-苄基或>N-杂环烷基；R8为烷基、芳基或杂环烷基，可选择性地取代；EWG代表从COOR、COSR、CONRR'、CN、COR、CF3、SOR、SO2R、SONRR'、SO2NRR'、NO2、卤素、杂环烷基组成的电子吸引基团；以及其药用盐或互变异构体。式(I)的化合物在治疗像阿尔茨海默病这样的神经退行性疾病中具有很强的作用。
• 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）。
• [EN] PROCESS FOR THE PREPARATION OF DONEPEZIL AND DERIVATIVES THEREOF<br/>[FR] PROCEDE DE PREPARATION DE DONEPEZIL ET DE SES DERIVES
  申请人：RANBAXY LAB LTD

  公开号：WO2004082685A1

  公开（公告）日：2004-09-30

  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甲基-茚烷酮的方法，以及使用这些化合物作为中间体制备苯甲基-哌啶甲基-茚烷酮，后者是治疗中枢神经系统疾病的活性化合物。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。