(R)-3-amino-1-(thiophen-2-yl)propan-1-ol | 858130-53-7

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (R)-3-amino-1-(thiophen-2-yl)propan-1-ol
• 英文别名: (1r)-3-Amino-1-(thiophen-2-yl)propan-1-ol；(1R)-3-amino-1-thiophen-2-ylpropan-1-ol
• CAS: 858130-53-7
• 化学式: C₇H₁₁NOS
• 分子量: 157.236
• InChiKey: OFOQLYYHEOJCSK-ZCFIWIBFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  10
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  74.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-3-amino-1-(thiophen-2-yl)propan-1-ol 在 lithium aluminium tetrahydride 、 偶氮二甲酸二异丙酯 、 potassium carbonate 、 三乙胺 、 三苯基膦 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 氯仿 为溶剂， 反应 28.0h， 生成 度洛西汀
  参考文献：
  名称：

  Chemoenzymatic synthesis of duloxetine and its enantiomer: lipase-catalyzed resolution of 3-hydroxy-3-(2-thienyl) propanenitrile

  摘要：

  An efficient and facile chemoenzymatic synthesis of duloxetine by lipase mediated resolution of 3-hydroxy-3-(2-thienyl)propanenitrile has been achieved. This process also describes an en antioconvergent synthesis of duloxetine via a Mitsunobu reaction. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(03)00945-6
• 作为产物：
  描述：

  2-氯乙酰噻吩 在 sodium tetrahydroborate 、 phosphate buffer 、 dimethyl sulfide borane 、 immobilised lipase from Pseudomonas cepacia 作用下， 以 四氢呋喃 、 甲醇 、 异丙醚 、 水 为溶剂， 反应 20.5h， 生成 (R)-3-amino-1-(thiophen-2-yl)propan-1-ol
  参考文献：
  名称：

  Chemoenzymatic synthesis of duloxetine and its enantiomer: lipase-catalyzed resolution of 3-hydroxy-3-(2-thienyl) propanenitrile

  摘要：

  An efficient and facile chemoenzymatic synthesis of duloxetine by lipase mediated resolution of 3-hydroxy-3-(2-thienyl)propanenitrile has been achieved. This process also describes an en antioconvergent synthesis of duloxetine via a Mitsunobu reaction. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(03)00945-6

文献信息

• [EN] AMINOPROPOXYPHENYL AND BENZYL 1-OXA-4,9-DIAZASPIROUNDECANE DERIVATIVES HAVING MULTIMODAL ACTIVITY AGAINST PAIN<br/>[FR] DÉRIVÉS D'AMINOPROPOXYPHÉNYLE ET DE BENZYL 1-OXA -4,9-DIAZASPIRO-UNDÉCANE AYANT UNE ACTIVITÉ MULTIMODALE CONTRE LA DOULEUR
  申请人：ESTEVE PHARMACEUTICALS SA

  公开号：WO2019180188A1

  公开（公告）日：2019-09-26

  The present invention relates to aminopropoxyphenyl and benzyl 1-oxa-4,9- diazaspiroundecanederivatives having dual pharmacological activity towards both the α2δ subunit, in particular the α2δ-1 subunit, of the voltage-gated calcium channel and the µ-opioid receptor, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.

  本发明涉及氨基丙氧基苯基和苄基1-氧杂-4,9-二氮杂螺十一烷衍生物，具有对电压门控钙通道的α2δ亚基，特别是α2δ-1亚基，和μ-阿片受体的双重药理活性，以及制备这些化合物的方法，包括它们的药物组合物，并且它们在治疗中的应用，特别是用于疼痛治疗。
• A Chemoenzymatic Dynamic Kinetic Resolution Approach to Enantiomerically Pure (<i>R</i>)- and (<i>S</i>)-Duloxetine
  作者：Annika Träff、Richard Lihammar、Jan-E. Bäckvall

  DOI：10.1021/jo2003665

  日期：2011.5.20

  The synthesis of (R)-duloxetine is described. Dynamic kinetic resolution of β-hydroxynitrile rac-1 using Candida antarctica lipase B (CALB, N435) and ruthenium catalyst 6 afforded β-cyano acetate (R)-2 in high yield and in excellent enantioselectivity (98% ee). The subsequent synthetic steps were straightforward and (R)-duloxetine was isolated in 37% overall yield over 6 steps. The synthetic route

  描述了（R）-度洛西汀的合成。使用南极假丝酵母脂肪酶B（CALB，N435）和钌催化剂6动态动力学拆分β-羟基腈rac - 1可以高收率和出色的对映选择性（98％ee）获得β-氰基乙酸酯（R）-2。随后的合成步骤是简单的，并且在6个步骤中以37％的总收率分离了（R）-度洛西汀。合成途径也构成了（S）-度洛西汀的正式全合成。
• [EN] AMINOPROPOXYPIPERIDINYLAMIDO DERIVATIVES HAVING MULTIMODAL ACTIVITY AGAINST PAIN<br/>[FR] DÉRIVÉS D'AMINOPROPOXYPIPÉRIDINYLAMIDO AYANT UNE ACTIVITÉ MULTIMODALE CONTRE LA DOULEUR
  申请人：ESTEVE PHARMACEUTICALS SA

  公开号：WO2019149919A1

  公开（公告）日：2019-08-08

  The present invention relates to aminopropoxyphenylpiperidinylamidoderivatives having dual pharmacological activity towards both the α2δ subunit, in particular the α2δ-1 subunit, of the voltage-gated calcium channel and the µ-opioid receptor, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.

  本发明涉及氨基丙氧基苯基哌啶酰胺衍生物，具有对电压门控钙通道α2δ亚基，特别是α2δ-1亚基，和µ-阿片受体的双重药理活性，涉及制备这类化合物的方法，包括它们的药物组合物以及在治疗中的应用，特别是用于疼痛治疗。
• Polymer-supported chiral sulfonamide catalyzed one-pot reduction of β-keto nitriles: a practical synthesis of (R)-fluoxetine and (R)-duloxetine
  作者：Guangyin Wang、Xingshun Liu、Gang Zhao

  DOI：10.1016/j.tetasy.2005.04.002

  日期：2005.5

  Enantioselective reduction of β-keto nitriles to optically active 1,3-amino alcohols has been carried out in one step using an excess of borane–dimethyl sulfide complex as a reductant and a polymer-supported chiral sulfonamide as a catalyst with moderate to high enantioselectivity. The facile and enantioselective method to prepare optically active 1,3-amino alcohols to be converted into 3-aryloxy-

  使用过量的硼烷-二甲硫醚络合物作为还原剂和聚合物负载的手性磺酰胺作为中等至高对映选择性的催化剂，已一步一步将β-酮腈对映体还原为光学活性1,3-氨基醇。还报道了制备旋光的1，3-氨基醇以转化为3-芳氧基-3-芳基丙胺型抗抑郁药（R）-氟西汀和（R）-度洛西汀的简便且对映选择性的方法。
• Inhibition of serotonin and norepinephrine reuptake and inhibition of phosphodiesterase by multi-target inhibitors as potential agents for depression
  作者：John R. Cashman、Senait Ghirmai

  DOI：10.1016/j.bmc.2009.08.025

  日期：2009.10

  Compounds possessing more than one functional activity incorporated into the same molecule may have advantages in treating complex disease states. Balanced serotonin/norepinephrine reuptake inhibitors (SNRIs) (i.e., (R)- and (S)-norduloxetine) were chemically linked to a PDE4 inhibitor via a five carbon bridge. The new dual SNRI/PDE4 inhibitors (i.e., (R)-15 and (S)-15) showed moderately potent serotonin reuptake inhibition (IC(50) values of 442 and 404 nM, respectively) but low reuptake inhibition of norepinephrine (IC(50) values of 2097 and 2190 nM, respectively) in vitro. The dual SNRI/PDE4 inhibitors (i.e., (R)-15 and (S)-15) also inhibited PDE4D2 (i.e., K(i) values of 23 and 45 nM, respectively). Due to their synergistic functional activity, SNRI/PDE4 inhibitors may be effective in treating diseases such as depression. (C) 2009 Elsevier Ltd. All rights reserved.