Duloxetine oxalate | 116817-77-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: Duloxetine oxalate
• 英文别名: (S)-(+)-N-methyl-3-(naphthalen-1-yloxy)-3-(thiophen-2-yl)propan-1-amine oxalate；(+)-(S)-N-methyl-3-(naphthalen-1-yloxy)-3-(thiophen-2-yl)propylamine oxalate；(S)-(+)-N-methyl-3-(1-naphthalenyloxy)-3-(2-thienyl) propanamine oxalate；(S)-(+)-N-methyl-3-(1-naphthalenyloxy)-3-(2-thienyl)propanamine oxalate；(+)-duloxetine oxalate；(S)-duloxetine oxalate；(3S)-N-methyl-3-naphthalen-1-yloxy-3-thiophen-2-ylpropan-1-amine;oxalic acid
• CAS: 116817-77-7
• 化学式: C₂H₂O₄*C₁₈H₁₉NOS
• 分子量: 387.456
• InChiKey: NMLRFGBDXFMJJM-LMOVPXPDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.79
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  124
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Duloxetine oxalate 在 sodium hydroxide 、 水 作用下， 生成 度洛西汀
  参考文献：
  名称：

  Process for the preparation of enantiomerically pure 3-hydroxy-3-arylpropylamines and their optical stereoisomers

  摘要：

  该发明提供了一种通过含有o-羧基苯甲酰基团的新型半酯衍生物作为中间体制备对映纯3-羟基-3-芳基丙胺的方法。3-羟基-3-芳基丙胺可用作制备血清素或去甲肾上腺素再摄取抑制剂，如度洛西汀、阿托莫西汀、氟西汀、尼索西汀和诺氟西汀的前体。

  公开号：

  EP2060559A1
• 作为产物：
  描述：

  1-氟萘 在 sodium hydride 、 N,N-二异丙基乙胺 、 potassium hydroxide 作用下， 以 polyethylene glycol-400 、 二甲基亚砜 、 乙酸乙酯 、 丙酮 、 甲苯 、 mineral oil 为溶剂， 反应 65.67h， 生成 Duloxetine oxalate
  参考文献：
  名称：

  [EN] AN IMPROVED PROCESS FOR THE PREPARATION OF DULOXETINE HYDROCHLORIDE
  [FR] PROCÉDÉ AMÉLIORÉ POUR LA PRÉPARATION DE CHLORHYDRATE DE DULOXÉTINE

  摘要：

  本公开提供了解决制备度洛西汀盐酸盐时出现的问题的解决方案。本公开成功地防止了外消旋和因此防止了度洛西汀盐酸盐的非期望异构体的形成。此外，本公开提供了一种简单的技术，用于去除在过程中用作反应物的1-氟萘反应物中未反应的反应物，以获得式（VI）化合物，即（S）-（+）-N-甲基-3（1-萘氧基）-3-（2-噻吩基）丙胺盐酸盐。

  公开号：

  WO2011077443A1

文献信息

• AMINOTHIAZOLONES AS ESTROGEN RELATED RECEPTOR-ALPHA MODULATORS
  申请人：Bignan Gilles

  公开号：US20110200587A1

  公开（公告）日：2011-08-18

  The present invention relates to compounds of Formula (I), methods for preparing these compounds, compositions, intermediates and derivatives thereof and for treating a condition including but not limited to ankylosing spondylitis, artherosclerosis, arthritis (such as rheumatoid arthritis, infectious arthritis, childhood arthritis, psoriatic arthritis, reactive arthritis), bone-related diseases (including those related to bone formation), breast cancer (including those unresponsive to anti-estrogen therapy), cardiovascular disorders, cartilage-related disease (such as cartilage injury/loss, cartilage degeneration, and those related to cartilage formation), chondrodysplasia, chondrosarcoma, chronic back injury, chronic bronchitis, chronic inflammatory airway disease, chronic obstructive pulmonary disease, diabetes, disorders of energy homeostasis, gout, pseudogout, lipid disorders, metabolic syndrome, multiple myeloma, obesity, osteoarthritis, osteogenesis imperfecta, osteolytic bone metastasis, osteomalacia, osteoporosis, Paget's disease, periodontal disease, polymyalgia rheumatica, Reiter's syndrome, repetitive stress injury, hyperglycemia, elevated blood glucose level, and insulin resistance.

  本发明涉及式(I)的化合物，制备这些化合物的方法，组合物，中间体及其衍生物，并用于治疗包括但不限于强直性脊柱炎、动脉粥样硬化、关节炎（如类风湿关节炎、感染性关节炎、儿童关节炎、银屑病性关节炎、反应性关节炎）、与骨相关的疾病（包括与骨形成有关的疾病）、乳腺癌（包括对抗雌激素治疗无效的癌症）、心血管疾病、软骨相关疾病（如软骨损伤/丧失、软骨退化以及与软骨形成有关的疾病）、软骨发育不全、软骨肉瘤、慢性背部损伤、慢性支气管炎、慢性炎症性气道疾病、慢性阻塞性肺病、糖尿病、能量稳态紊乱、痛风、假性痛风、脂质紊乱、代谢综合征、多发性骨髓瘤、肥胖、骨关节炎、遗传性骨发育不全、骨溶解性骨转移、软骨软化症、骨质疏松症、帕金森病、牙周病、多肌痛风、Reiter综合征、重复性应激损伤、高血糖、血糖水平升高和胰岛素抵抗等疾病的方法。
• SUBSTITUTED AMINOTHIAZOLONE INDAZOLES AS ESTROGEN RELATED RECEPTOR-ALPHA MODULATORS
  申请人：BIGNAN Gilles

  公开号：US20110150864A1

  公开（公告）日：2011-06-23

  The present invention relates to compounds of Formula (I), methods for preparing these compounds, compositions, intermediates and derivatives thereof and for treating a condition including but not limited to ankylosing spondylitis, artherosclerosis, arthritis (such as rheumatoid arthritis, infectious arthritis, childhood arthritis, psoriatic arthritis, reactive arthritis), bone-related diseases (including those related to bone formation), breast cancer (including those unresponsive to anti-estrogen therapy), cardiovascular disorders, cartilage-related disease (such as cartilage injury/loss, cartilage degeneration, and those related to cartilage formation), chondrodysplasia, chondrosarcoma, chronic back injury, chronic bronchitis, chronic inflammatory airway disease, chronic obstructive pulmonary disease, diabetes, disorders of energy homeostasis, gout, pseudogout, lipid disorders, metabolic syndrome, multiple myeloma, obesity, osteoarthritis, osteogenesis imperfecta, osteolytic bone metastasis, osteomalacia, osteoporosis, Paget's disease, periodontal disease, polymyalgia rheumatica, Reiter's syndrome, repetitive stress injury, hyperglycemia, elevated blood glucose level, and insulin resistance.

  该发明涉及式(I)的化合物，制备这些化合物的方法，组合物，中间体及其衍生物，并用于治疗包括但不限于强直性脊柱炎、动脉粥样硬化、关节炎（如类风湿性关节炎、感染性关节炎、儿童关节炎、银屑病性关节炎、反应性关节炎）、与骨相关的疾病（包括与骨形成有关的疾病）、乳腺癌（包括对抗雌激素治疗无效的癌症）、心血管疾病、软骨相关疾病（如软骨损伤/丧失、软骨退化以及与软骨形成有关的疾病）、软骨发育不良、软骨肉瘤、慢性腰部损伤、慢性支气管炎、慢性炎症性气道疾病、慢性阻塞性肺疾病、糖尿病、能量稳态紊乱、痛风、假性痛风、脂质紊乱、代谢综合征、多发性骨髓瘤、肥胖、骨关节炎、遗传性骨发育不全、骨转移性溶骨性转移、软骨软化症、骨质疏松症、帕金森病、牙周病、多肌痛风、Reiter综合征、重复性应激损伤、高血糖、血糖水平升高和胰岛素抵抗等疾病的条件。
• SUBSTITUTED THIAZOLIDINEDIONE INDAZOLES, INDOLES AND BENZOTRIAZOLES AS ESTROGEN-RELATED RECEPTOR-a MODULATORS
  申请人：Bignan Gilles

  公开号：US20110294780A1

  公开（公告）日：2011-12-01

  The present invention relates to compounds of Formula (I), methods for preparing these compounds, compositions, intermediates and derivatives thereof and for treating a condition including but not limited to ankylosing spondylitis, artherosclerosis, arthritis (such as rheumatoid arthritis, infectious arthritis, childhood arthritis, psoriatic arthritis, reactive arthritis), bone-related diseases (including those related to bone formation), breast cancer (including those unresponsive to anti-estrogen therapy), cardiovascular disorders, cartilage-related disease (such as cartilage injury/loss, cartilage degeneration, and those related to cartilage formation), chondrodysplasia, chondrosarcoma, chronic back injury, chronic bronchitis, chronic inflammatory airway disease, chronic obstructive pulmonary disease, diabetes, disorders of energy homeostasis, gout, pseudogout, lipid disorders, metabolic syndrome, multiple myeloma, obesity, osteoarthritis, osteogenesis imperfecta, osteolytic bone metastasis, osteomalacia, osteoporosis, Paget's disease, periodontal disease, polymyalgia rheumatica, Reiter's syndrome, repetitive stress injury, hyperglycemia, elevated blood glucose level, and insulin resistance.

  本发明涉及式(I)的化合物，制备这些化合物的方法，组合物，中间体及其衍生物，并用于治疗包括但不限于强直性脊柱炎，动脉粥样硬化，关节炎（如类风湿关节炎，感染性关节炎，儿童关节炎，银屑病性关节炎，反应性关节炎），与骨相关的疾病（包括与骨形成有关的疾病），乳腺癌（包括对抗雌激素治疗无效的癌症），心血管疾病，软骨相关疾病（如软骨损伤/丧失，软骨退化以及与软骨形成有关的疾病），软骨发育不良，软骨肉瘤，慢性腰部损伤，慢性支气管炎，慢性炎症性气道疾病，慢性阻塞性肺疾病，糖尿病，能量稳态紊乱，痛风，假性痛风，脂质紊乱，代谢综合征，多发性骨髓瘤，肥胖，骨关节炎，遗传性骨发育不全，骨溶解性骨转移，软骨软化症，骨质疏松症，帕金森病，牙周病，多肌痛风，Reiter综合征，重复性应激损伤，高血糖，血糖水平升高和胰岛素抵抗等病症的方法。
• Method for producing enantiomer-pure aminoalcohols
  申请人：Sturmer Rainer

  公开号：US20070128704A1

  公开（公告）日：2007-06-07

  The invention relates to a process for preparing enantiomerically pure alcohol of the formula 1, which comprises (i) reducing the ketone of the formula 3 to the racemic alcohol of the formula 4, (ii) enantioselectively acylating the racemic alcohol of the formula 4 with succinic anhydride in the presence of a lipase to give the succinic semiester of the formula 7, (iii) separating off the succinic semiester of the formula 7 from the unreacted enantiomer of the formula 4, (iv) reacting the enantiomerically pure alcohol of the formula 4 with methylamine to give the enantiomerically pure alcohol of the formula 1.

  该发明涉及一种制备式1对映纯醇的过程，包括（i）将式3的酮还原为式4的消旋醇，（ii）在脂肪酶存在下对式4的消旋醇进行对映选择性酰化，以得到式7的琥珀酸半酯，（iii）将式7的琥珀酸半酯与未反应的式4的对映体分离，（iv）将对映纯醇式4与甲胺反应，得到对映纯醇式1。
• [DE] 3-METHYLAMINO-1-(2-THIENYL)-1-PROPANON, SEINE HERSTELLUNG UND VERWENDUNG<br/>[EN] 3-METHYLAMINO-1-(2-THIENYL)-1-PROPANONE, PRODUCTION AND USE THEREOF<br/>[FR] 3-METHYLAMINO-1-(2-THIENYLE)-1-PROPANONE, SA PRODUCTION ET SON UTILISATION
  申请人：BASF AG

  公开号：WO2004065376A1

  公开（公告）日：2004-08-05

  Die vorliegende Erfindung betrifft die Herstellung von 3-Methylamino-1-(2-thienyl)-1propanon und seine Verwendung zur Herstellung des Pharmazeutikums (+)-(S)-Nmethyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine oxalat - (Handelsname Duloxetine®).

  本发明涉及3-甲基氨基-1-(2-噻吩基)-1-丙酮的制备及其用于制备药物(+)-(S)-N-甲基-3-(1-萘氧基)-3-(2-噻吩基)丙胺草酸盐-（商品名度洛西汀®）的用途。