(1S,2R)-1-(3-fluorophenyl)-1-(3-isopropyl-2,3-dihydro-1H-indol-1-yl)-3-(methylamino)propan-2-ol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (1S,2R)-1-(3-fluorophenyl)-1-(3-isopropyl-2,3-dihydro-1H-indol-1-yl)-3-(methylamino)propan-2-ol
• 英文别名: (1S,2R)-1-(3-Fluorophenyl)-1-(3-isopropyl-2,3-dihydro-1Hindol-1-yl)-3-(methylamino)propan-2-ol Hydrochloride；(1S,2R)-1-(3-fluorophenyl)-3-(methylamino)-1-(3-propan-2-yl-2,3-dihydroindol-1-yl)propan-2-ol
• 化学式: C₂₁H₂₇FN₂O
• 分子量: 342.457
• InChiKey: BFQOTQMSOCASOW-HBYOEVMUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  35.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1S,2R)-1-(3-fluorophenyl)-1-(3-isopropyl-2,3-dihydro-1H-indol-1-yl)-3-(methylamino)propan-2-ol 在 盐酸 作用下， 以 乙醚 、 乙醇 、 异丙醚 为溶剂， 生成 (1S,2R)-1-(3-fluorophenyl)-1-(3-isopropyl-2,3-dihydro-1H-indol-1-yl)-3-(methylamino)propan-2-ol hydrochloride
  参考文献：
  名称：

  1-(Indolin-1-yl)-1-phenyl-3-propan-2-olamines as Potent and Selective Norepinephrine Reuptake Inhibitors

  摘要：

  Efforts to identify new selective and potent norepinephrine reuptake inhibitors (NRIs) For multiple indications by structural modification of the previous 3-(arylamino)-3-phenylpropan-2-olamine scaffold led to the discovery of it novel series of 1-(indolin-1-yl)-1-phenyl-3-propan-2-olamines (9). Investigation of the structure-activity relationships revealed that small alkyl substitution at the C3 position of the indoline ring enhanced selectivity for the norepinephrine transporter (NET) over the serotonin transporter (SERT). Several compounds bearing a 3,3-dimethyl group on the indoline ring, 9k, 9o,p, and 9s,t, exhibited potent inhibition of NET (IC(50) = 2.7-6.5 nM) and excellent selectivity over both serotonin and dopamine transporters. The best example from this series, 9p, a potent and highly selective NRI, displayed oral efficacy In a telemetric rat model of ovariectomized-induced thermoregulatory dysfunction, it mouse p-phenylquinone (PPQ) model of acute visceral pain, and a rat spinal nerve ligation (SNL) model of neuropathic pain.

  DOI：

  10.1021/jm901559e
• 作为产物：
  描述：

  (2S,3S)-3-(3-fluorophenyl)-3-(3-isopropyl-2,3-dihydro-1H-indol-1-yl)propane-1,2-diol 、 甲胺 在 三乙胺 、 对甲苯磺酰氯 作用下， 以 二氯甲烷 、 乙醇 为溶剂， 反应 6.0h， 生成 (1S,2R)-1-(3-fluorophenyl)-1-(3-isopropyl-2,3-dihydro-1H-indol-1-yl)-3-(methylamino)propan-2-ol
  参考文献：
  名称：

  1-(Indolin-1-yl)-1-phenyl-3-propan-2-olamines as Potent and Selective Norepinephrine Reuptake Inhibitors

  摘要：

  Efforts to identify new selective and potent norepinephrine reuptake inhibitors (NRIs) For multiple indications by structural modification of the previous 3-(arylamino)-3-phenylpropan-2-olamine scaffold led to the discovery of it novel series of 1-(indolin-1-yl)-1-phenyl-3-propan-2-olamines (9). Investigation of the structure-activity relationships revealed that small alkyl substitution at the C3 position of the indoline ring enhanced selectivity for the norepinephrine transporter (NET) over the serotonin transporter (SERT). Several compounds bearing a 3,3-dimethyl group on the indoline ring, 9k, 9o,p, and 9s,t, exhibited potent inhibition of NET (IC(50) = 2.7-6.5 nM) and excellent selectivity over both serotonin and dopamine transporters. The best example from this series, 9p, a potent and highly selective NRI, displayed oral efficacy In a telemetric rat model of ovariectomized-induced thermoregulatory dysfunction, it mouse p-phenylquinone (PPQ) model of acute visceral pain, and a rat spinal nerve ligation (SNL) model of neuropathic pain.

  DOI：

  10.1021/jm901559e

文献信息

• Phenylaminopropanol derivatives and methods of their use
  申请人：Mahaney Erin Paige

  公开号：US20070072897A1

  公开（公告）日：2007-03-29

  The present invention is directed to phenylaminopropanol derivatives of formulae I, II, and III: or a pharmaceutically acceptable salt thereof, compositions containing these derivatives, and methods of their use for the prevention and treatment of conditions ameliorated by monoamine reuptake including, inter alia, vasomotor symptoms (VMS), sexual dysfunction, gastrointestinal and genitourinary disorders, chronic fatigue syndrome, fibromyalgia syndrome, nervous system disorders, and combinations thereof, particularly those conditions selected from the group consisting of major depressive disorder, vasomotor symptoms, stress and urge urinary incontinence, fibromyalgia, pain, diabetic neuropathy, schizophrenia, and combinations thereof.

  本发明涉及具有以下结构的苯基氨基丙醇衍生物：或其药学上可接受的盐、含有这些衍生物的组合物，以及它们用于预防和治疗由单胺再摄取改善的病况的方法，包括但不限于血管运动症状（VMS）、性功能障碍、胃肠和泌尿系统疾病、慢性疲劳综合征、纤维肌痛综合征、神经系统疾病和其组合，特别是从以下组中选出的主要抑郁症、血管运动症状、压力性和切欲性尿失禁、纤维肌痛、疼痛、糖尿病神经病变、精神分裂症和其组合。
• 1- (1H- INDOL- 1-YL) -3- (METHYLAMINO) -1- PHENYLPROPAN-2-OL DERIVATIVES AND RELATED COMPOUNDS AS MODULATORS OF THE MONOAMINE REUPTAKE FOR THE TREATMENT OF VASOMOTOR SYMPTOMS (VMS)
  申请人：Wyeth

  公开号：EP1931631A1

  公开（公告）日：2008-06-18
• [EN] 1- (1H- INDOL- 1-YL) -3- (METHYLAMINO) -1- PHENYLPROPAN-2-OL DERIVATIVES AND RELATED COMPOUNDS AS MODULATORS OF THE MONOAMINE REUPTAKE FOR THE TREATMENT OF VASOMOTOR SYMPTOMS (VMS)<br/>[FR] DERIVES DE 1- (1H- INDOL- 1-YL) -3- (METHYLAMINO) -1- PHENYLPROPAN-2-OL ET COMPOSES ASSOCIES UTILISES COMME MODULATEURS DU RECAPTAGE DE MONOAMINE POUR TRAITER DES SYMPTOMES VASOMOTEURS (VMS)
  申请人：WYETH CORP

  公开号：WO2007041023A1

  公开（公告）日：2007-04-12

  [EN] The present invention is directed to phenylaminopropanol derivatives of formulae (I), (II), and (III); or a pharmaceutically acceptable salt thereof, compositions containing these derivatives, and methods of their use for the prevention and treatment of conditions ameliorated by monoamine reuptake including, inter alia, vasomotor symptoms (VMS), sexual dysfunction, gastrointestinal and genitourinary disorders, chronic fatigue syndrome, fibromylagia syndrome, nervous system disorders, and combinations thereof, particularly those conditions selected from the group consisting of major depressive disorder, vasomotor symptoms, stress and urge urinary incontinence, fibromyalgia, pain, diabetic neuropathy, schizophrenia, and combinations thereof.
  [FR] L'invention concerne des dérivés de phénylaminopropanol représentés par les formules (I), (II) et (III) ou des sels de ces dérivés pharmaceutiquement acceptables, des compositions contenant lesdits dérivés, et leurs méthodes d'utilisation pour prévenir et traiter des états améliorés par le recaptage de monoamine, comprenant notamment, les symptômes vasomoteurs (VMS), le dysfonctionnement sexuel, les troubles gastro-intestinaux et génito-urinaires, le syndrome de la fatigue chronique, le syndrome de la fibromyalgie, les troubles du système nerveux et des combinaisons de ces pathologies, en particulier les états sélectionnés dans le groupe constitué par les troubles dépressifs majeurs, les symptômes vasomoteurs, le stress et l'incontinence urinaire insistante, la fibromyalgie, la douleur, la neuropathie diabétique, la schizophrénie et des combinaisons de ces pathologies.
• 1-(Indolin-1-yl)-1-phenyl-3-propan-2-olamines as Potent and Selective Norepinephrine Reuptake Inhibitors
  作者：An T. Vu、Stephen T. Cohn、Puwen Zhang、Callain Y. Kim、Paige E. Mahaney、Jenifer A. Bray、Grace H. Johnston、Elizabeth J. Koury、Scott A. Cosmi、Darlene C. Deecher、Valerie A. Smith、James E. Harrison、Liza Leventhal、Garth T. Whiteside、Jeffrey D. Kennedy、Eugene J. Trybulski

  DOI：10.1021/jm901559e

  日期：2010.3.11

  Efforts to identify new selective and potent norepinephrine reuptake inhibitors (NRIs) For multiple indications by structural modification of the previous 3-(arylamino)-3-phenylpropan-2-olamine scaffold led to the discovery of it novel series of 1-(indolin-1-yl)-1-phenyl-3-propan-2-olamines (9). Investigation of the structure-activity relationships revealed that small alkyl substitution at the C3 position of the indoline ring enhanced selectivity for the norepinephrine transporter (NET) over the serotonin transporter (SERT). Several compounds bearing a 3,3-dimethyl group on the indoline ring, 9k, 9o,p, and 9s,t, exhibited potent inhibition of NET (IC(50) = 2.7-6.5 nM) and excellent selectivity over both serotonin and dopamine transporters. The best example from this series, 9p, a potent and highly selective NRI, displayed oral efficacy In a telemetric rat model of ovariectomized-induced thermoregulatory dysfunction, it mouse p-phenylquinone (PPQ) model of acute visceral pain, and a rat spinal nerve ligation (SNL) model of neuropathic pain.