5-甲氧基-2-(吡啶-4-甲基)-2,3-二氢-1H-茚-1-酮 | 154932-68-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 中文名称: 5-甲氧基-2-(吡啶-4-甲基)-2,3-二氢-1H-茚-1-酮
• 中文别名: 5-甲氧基-2-(吡啶基-4-甲基)-2,3-二氢-1H-茚-1-酮
• 英文名称: 5-Methoxy-2-pyridin-4-ylmethyl-indan-1-one
• 英文别名: 5-methoxy-2-(pyridin-4-ylmethyl)-2,3-dihydro-1H-inden-1-one；5-methoxy-2-(pyridin-4-ylmethyl)-2,3-dihydroinden-1-one
• CAS: 154932-68-0
• 化学式: C₁₆H₁₅NO₂
• 分子量: 253.301
• InChiKey: HKUPXKYZDOQZHE-UHFFFAOYSA-N

物化性质

• 沸点：
  446.3±40.0 °C(Predicted)
• 密度：
  1.203±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  5-甲氧基-2-(吡啶-4-甲基)-2,3-二氢-1H-茚-1-酮 在 氢氧化钾 、 一水合肼 作用下， 生成 4-((5-甲氧基-2,3-二氢-1H-茚-2-基)甲基)吡啶
  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：

  5-甲氧基-1-茚酮 在 palladium on activated charcoal 哌啶 、 氢气 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 1.5h， 生成 5-甲氧基-2-(吡啶-4-甲基)-2,3-二氢-1H-茚-1-酮
  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

• Hartmann Rolf W., Bayer Herbert, Gruen Gertrud, J. Med. Chem, 37 (1994) N 9, S 1275-1281
  作者：Hartmann Rolf W., Bayer Herbert, Gruen Gertrud

  DOI：——

  日期：——
• PROCESS FOR PRODUCTION OF DONEPEZIL DERIVATIVES
  申请人：Eisai Co., Ltd.

  公开号：EP1047674B1

  公开（公告）日：2005-03-30
• EP1531806A4
  申请人：——

  公开号：EP1531806A4

  公开（公告）日：2005-09-21
• USE OF THIO-OXINDOLE DERIVATIVES IN TREATMENT OF HORMONE-RELATED CONDITIONS
  申请人：Wyeth

  公开号：EP1531806A2

  公开（公告）日：2005-05-25
• [EN] USE OF THIO-OXINDOLE DERIVATIVES IN TREATMENT OF HORMONE-RELATED CONDITIONS<br/>[FR] UTILISATION DE DERIVES DE THIO-OXINDOLE DANS LE TRAITEMENT D'ETATS PATHOLOGIQUES LIES AUX HORMONES
  申请人：WYETH CORP

  公开号：WO2004000225A2

  公开（公告）日：2003-12-31

  The present invention provides methods of inducing contraception which includes delivering to a female a composition containing a compound of formula (I), or tautomers thereof, in a regimen which involves delivering one or more of a selective estrogen receptor modulator, wherein formula (I) and wherein R1-R5 and Q1 are defined as described herein. Methods of providing hormone replacement therapy and for treating carcinomas, dysfunctional bleeding, uterine leiomyomata, endometriosis, and polycystic ovary syndrome is provided which includes delivering a compound of formula I and a selective estrogen receptor modulator are also described.