3-(dimethylamino)-1-(4-fluorophenyl)propan-1-ol | 133712-56-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(dimethylamino)-1-(4-fluorophenyl)propan-1-ol
• CAS: 133712-56-8
• 化学式: C₁₁H₁₆FNO
• 分子量: 197.253
• InChiKey: HXKHYYJUHCVYMI-UHFFFAOYSA-N

物化性质

• 沸点：
  288.2±30.0 °C(Predicted)
• 密度：
  1.086±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(dimethylamino)-1-(4-fluorophenyl)propan-1-ol 在 2,4-滴二甲胺盐 、 sodium hydride 作用下， 以 苯 为溶剂， 生成
  参考文献：
  名称：

  Duloxetine (Cymbalta™), a dual inhibitor of serotonin and norepinephrine reuptake

  摘要：

  A series of naphthalenyloxy-arylpropylamines have been prepared and are demonstrated to be inhibitors of both serotonin and norepinephrine reuptake. One member of this series, duloxetine (Cymbalta(TM)) has proven to be effective in clinical trials for the treatment of depression. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.08.079
• 作为产物：
  描述：

  4-氟苯乙酮 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 6.0h， 生成 3-(dimethylamino)-1-(4-fluorophenyl)propan-1-ol
  参考文献：
  名称：

  以脂肪胺为供体的分子内激基复合物的电子结构

  摘要：

  摘要 研究了脂肪族叔胺与苯基之间的分子内激基复合物形成。确定了脂肪族链长和苯基部分的对位取代对激基复合物性质（荧光、速率常数、形成速率常数）的影响。结果与电荷转移和激复合物的局部激发态的相对贡献定性相关。还证明了通过氮原子上的正电荷分裂苯基 LUMO 的简并性。

  DOI：

  10.1016/0022-2860(82)85265-4

文献信息

• [EN] SUBSTITUTED 3-HETEROARYLOXY-3-(HETERO)ARYL-PROPYLAMINES AS SEROTONIN TRANSPORTER AND SEROTONIN HT2C RECEPTOR MODULATORS<br/>[FR] 3-HÉTÉROARYLOXY-3-(HÉTÉRO)ARYL-PROPYLAMINES SUBSTITUÉES COMME MODULATEURS DE TRANSPORTEUR DE LA SÉROTONINE ET DU RÉCEPTEUR HT2C DE LA SÉROTONINE
  申请人：AAPA B V

  公开号：WO2014046544A1

  公开（公告）日：2014-03-27

  The present invention relates to compounds compound according to Formula (1): and pharmaceutically acceptable salts, hydrates and solvates thereof. These compounds have serotonin (5-HT) transporter inhibitory effects and 5-HT 2C receptor antagonist or inverse agonist effects. The present invention also relates to pharmaceutical compositions comprising these compounds, and methods of using them for application in the prophylaxis or treatment of CNS disorders.

  本发明涉及按照式（1）的化合物和其药学上可接受的盐、水合物和溶剂合物。这些化合物具有血清素（5-HT）转运体抑制作用和5-HT 2C 受体拮抗剂或逆激动剂作用。本发明还涉及包含这些化合物的药物组合物，以及将它们用于预防或治疗中枢神经系统疾病的方法。
• Synthesis and pharmacological investigation of aralkyl diamine derivatives as potential triple reuptake inhibitors
  作者：Yong-Yong Zheng、Zhi-Jie Weng、Peng Xie、Mei-Yu Zhu、Long-Xuan Xing、Jian-Qi Li

  DOI：10.1016/j.ejmech.2014.08.045

  日期：2014.10

  A series of aralkyl diamine derivatives were designed, synthesized, and evaluated for their triple reuptake inhibitory abilities. Compounds 18c (5-HT, NE, DA, IC50 = 389, 69, 238 nM), 36a (5-HT, NE, DA, IC50 = 378, 477, 247 nM), and 36d (5-HT, NE, DA, IC50 = 501, 206, 357 nM) showed in vivo activities in the rat forced swim test at 5, 10, and 20 mg/kg PO. 36a was identified as the most promising candidate

  设计，合成了一系列芳烷基二胺衍生物，并对其三重再摄取抑制能力进行了评估。化合物18c（5-HT，NE，DA，IC 50  = 389，69，238 nM），36a（5-HT，NE，DA，IC 50  = 378，477，247 nM）和36d（5-HT， NE，DA，IC 50  = 501、206、357 nM）在大鼠强迫游泳试验中以5、10和20 mg / kg PO表现出体内活性。36a被确定为本研究中最有前途的候选人。具体而言，36a对许多中枢神经系统相关靶标的单胺转运蛋白表现出高选择性。此外，36a 在临床前研究中显示出良好的药代动力学性质和可接受的安全性。
• Aryloxyphenylpropylamines their preparation and use
  申请人：Novo Nordisk A/S

  公开号：US05145870A1

  公开（公告）日：1992-09-08

  Novel aryloxyphenylpropylamines having the formula ##STR1## wherein X is H, cyano, halogen, halogenoalkyl, C.sub.1-6 -alkoxy, C.sub.1-6 -alkyl, C.sub.1-5 -alkanoyl, C.sub.3-5 -alkylene, aryloxy or aralkoxy, and R is 3,4-methylenedioxy, aryl or heteroaryl which are optionally substituted with one or more cyano, halogeno, C.sub.1-6 -alkyl, C.sub.1-6 -alkoxy, C.sub.1-6 -alkenyl, trifluoromethyl, C.sub.3-5 -alkylene, aryloxy or aralkoxy; and R.sup.1 and R.sup.2 independently is C.sub.1-10 -alkyl, C.sub.3-7 -cycloalkyl, C.sub.2-10 -alkenyl, C.sub.3-6 -cycloalkyl-C.sub.1-5 -alkyl, optionally substituted with C.sub.1-5 -alkoxy or cyano; R.sup.1 and R.sup.2 may together form a carbocyclic ring and a salt thereof with a pharmaceutically acceptable acid, provided however that R.sup.1 is not C.sub.3-7 -cycloalkyl, C.sub.1-10 -alkyl, or alkenyl which may be straight, branched or cyclic, unsubstituted or substituted with C.sub.1-4 -alkoxy, aryloxy or cycloalkyl or cycloalkylalkyl, when X is H and R.sup.2 is a methyl group. The novel compounds are useful in the treatment of anoxia, migraine, ischemia, epilepsy, traumatic injury and neurodegenerative diseases.

  具有以下结构式的新型芳基氧基苯基丙胺类化合物，其中X为H、氰基、卤素、卤代烷基、C.sub.1-6-烷氧基、C.sub.1-6-烷基、C.sub.1-5-烷酰基、C.sub.3-5-烷基烯、芳基氧基或芳基烷氧基，R为3,4-亚甲二氧基、芳基或杂环芳基，可选地取代一个或多个氰基、卤代基、C.sub.1-6-烷基、C.sub.1-6-烷氧基、C.sub.1-6-烯基、三氟甲基、C.sub.3-5-烷基烯、芳基氧基或芳基烷氧基；R.sup.1和R.sup.2独立地为C.sub.1-10-烷基、C.sub.3-7-环烷基、C.sub.2-10-烯基、C.sub.3-6-环烷基-C.sub.1-5-烷基，可选地取代为C.sub.1-5-烷氧基或氰基；R.sup.1和R.sup.2可共同形成一个碳环，并与药用可接受的酸形成盐，但R.sup.1不为C.sub.3-7-环烷基、C.sub.1-10-烷基或烯基，可为直链、支链或环状，未取代或取代为C.sub.1-4-烷氧基、芳基氧基或环烷基或环烷基烷基，当X为H且R.sup.2为甲基基团时。这些新型化合物可用于治疗缺氧、偏头痛、缺血、癫痫、创伤性损伤和神经退行性疾病。
• 3-[(BENZO[D][1,3]DIOXOLAN-4-YL)-OXY]-3-ARYLPROPYLAMINE TYPE COMPOUNDS AND APPLICATIONS THEREOF
  申请人：NHWA PHARMA. CORPORATION

  公开号：US20170369466A1

  公开（公告）日：2017-12-28

  The present invention relates to 3-[(benzo[d][1,3]dioxolan-4-yl)-oxy]-3-arylpropylamine compounds of formula I or pharmaceutically acceptable salts thereof and use thereof. The compound may be used to prepare an antidepressant agent.

  本发明涉及公式I的3-[(苯并[d][1,3]二氧杂环戊烷-4-基)-氧基]-3-芳基丙胺化合物或其药用盐，以及其用途。该化合物可用于制备抗抑郁药物。
• [EN] NOVEL PROCESS FOR THE PREPARATION OF 4-ARYL-3-HYDROXYMETHYL-1-METHYLPIPERIDINES.<br/>[FR] NOUVEAU PROCEDE DE PREPARATION DE 4-ARYL-3-HYDROXYMETHYL-1-METHYLPIPERIDINES
  申请人：NATCO PHARMA LTD

  公开号：WO2004043921A1

  公开（公告）日：2004-05-27

  A novel, improved, and general process for the preparation of 4-aryl-3-hydroxymethyl-1-methylpiperidines is disclosed in the present invention. 4-(4-Fluorophenyl)-3-hydroxymethyl-1-methylpiperidine is a well-known intermediate in making the anti-depressant drug, paroxetine ((-)-trans-4-p-fluorophenyl-3-(3',4'-methylenedioxy-phenoxymethyl)piperidine). Novel N-methyl-N-[3-(4-substitutedphenyl (F, Me, OMe))-3-hydroxy]propylamines are prepared from the Mannich salts such as 3-dimethylamino- or 3-(N-methyl-N-benzylamino)-4'-substituted (F, Me, OMe) propiophenone hydrochlorides by conventional methods. The N-methyl-N-[3-(4-substitutedphenyl (H, F, Me, OMe))-3-hydroxy]propylamines thus obtained are reacted with ethyl or methyl acrylate to get the corresponding Michael addition products. The hydroxy group present in the Michael addition products is converted into a facile leaving group and treated with a strong base to get 4-aryl-N-methylpiperidine-3-carboxylates via the intramolecular cyclization in good yields. Reduction of the ester group present in these piperidine-3-carboxylates gave the title compounds as crystalline solids. Present process is easily adaptable for commercial preparation of the paroxetine intermediate (4-(4-fluorophenyl)-3-hydroxymethyl-1-methylpiperidine).

  本发明揭示了一种新颖的、改进的、通用的制备4-芳基-3-羟甲基-1-甲基哌啶的方法。4-(4-氟苯基)-3-羟甲基-1-甲基哌啶是制造抗抑郁药物帕罗西汀((-)-trans-4-p-氟苯基-3-(3',4'-亚甲二氧基苯氧甲基)哌啶)的已知中间体。新型的N-甲基-N-[3-(4-取代苯基(F，Me，OMe))-3-羟基]丙胺可通过常规方法从Mannich盐制备而来，例如3-二甲氨基或3-(N-甲基-N-苄基氨基)-4'-取代(F，Me，OMe)丙酮盐酸盐。因此获得的N-甲基-N-[3-(4-取代苯基(H，F，Me，OMe))-3-羟基]丙胺与乙基或甲基丙烯酸酯反应，得到相应的Michael加成产物。Michael加成产物中存在的羟基转化为容易离去的基团，并用强碱处理，通过分子内环化以良好的产率得到4-芳基-N-甲基哌啶-3-羧酸酯。这些哌啶-3-羧酸酯中存在的酯基还原后，得到了晶体固体的目标化合物。目前的方法易于用于商业制备帕罗西汀中间体(4-(4-氟苯基)-3-羟甲基-1-甲基哌啶)。