diethyl 2-[2-cyano-5-(dimethylamino)-2-(3-methoxyphenyl)-1,1-dimethylpentyl] propanedioate, monohydrochloride | 139138-96-8

• 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: diethyl 2-[2-cyano-5-(dimethylamino)-2-(3-methoxyphenyl)-1,1-dimethylpentyl] propanedioate, monohydrochloride
• 英文别名: Diethyl 2-[2-cyano-5-(dimethylamino)-2-(3-methoxy-phenyl)-1,1-dimethylpentyl]propanedioate, monohydrochloride；diethyl 2-[3-cyano-6-(dimethylamino)-3-(3-methoxyphenyl)-2-methylhexan-2-yl]propanedioate;hydrochloride
• CAS: 139138-96-8
• 化学式: C₂₄H₃₆N₂O₅*ClH
• 分子量: 469.021
• InChiKey: BDEZHINYUSGFBY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.99
• 重原子数：
  32
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  88.9
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  diethyl 2-[2-cyano-5-(dimethylamino)-2-(3-methoxyphenyl)-1,1-dimethylpentyl] propanedioate, monohydrochloride 在 硫酸 作用下， 以 水 为溶剂， 反应 54.0h， 生成 3-(3-methoxyphenyl)-3-(3-dimethylaminopropyl)-4,4-dimethyl-piperidine-2,6-dione bisulphate salt
  参考文献：
  名称：

  [EN] PIPERIDIN-2,6-DIONE PAMOATE SALTS AND THEIR USE FOR THE TREATMENT OF STRESS-RELATED AFFECTIVE DISORDERS
  [FR] PAMOATES DE PIPERIDINE-2,6-DIONE ET LEUR UTILISATION POUR LE TRAITEMENT DE TROUBLES AFFECTIFS EN LIAISON AVEC LE STRESS

  摘要：

  某些3-苯基-3-二甲基氨基烷基-4,4-二甲基哌啶-2,6-二酮（1）的帕莫酸盐及其药学上可接受的溶剂化物，在治疗或预防压力相关情感障碍，如焦虑、抑郁、偏头痛和睡眠呼吸暂停中，不会出现大鼠体重减轻和肝细胞变化，这限制了相应盐酸的允许临床剂量的边缘有效水平。首选的帕莫酸盐是3（3,5-二甲氧基苯基）-3-（3-二甲基氨丙基）-4,4-二甲基哌啶-2,6-二酮帕莫酸盐，尤其是3（3-甲氧基苯基）-3-（3-二甲基氨丙基）-4,4-二甲基哌啶-2,6-二酮帕莫酸盐。

  公开号：

  WO2004017970A1
• 作为产物：
  描述：

  亚异丙基丙二酸二乙酯 、 α-[3-(dimethylamino)propyl]-3-methoxybenzeneacetonitrile 、 lithium diisopropyl amide 在 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 1.0h， 生成 diethyl 2-[2-cyano-5-(dimethylamino)-2-(3-methoxyphenyl)-1,1-dimethylpentyl] propanedioate, monohydrochloride
  参考文献：
  名称：

  [EN] PIPERIDIN-2,6-DIONE PAMOATE SALTS AND THEIR USE FOR THE TREATMENT OF STRESS-RELATED AFFECTIVE DISORDERS
  [FR] PAMOATES DE PIPERIDINE-2,6-DIONE ET LEUR UTILISATION POUR LE TRAITEMENT DE TROUBLES AFFECTIFS EN LIAISON AVEC LE STRESS

  摘要：

  某些3-苯基-3-二甲基氨基烷基-4,4-二甲基哌啶-2,6-二酮（1）的帕莫酸盐及其药学上可接受的溶剂化物，在治疗或预防压力相关情感障碍，如焦虑、抑郁、偏头痛和睡眠呼吸暂停中，不会出现大鼠体重减轻和肝细胞变化，这限制了相应盐酸的允许临床剂量的边缘有效水平。首选的帕莫酸盐是3（3,5-二甲氧基苯基）-3-（3-二甲基氨丙基）-4,4-二甲基哌啶-2,6-二酮帕莫酸盐，尤其是3（3-甲氧基苯基）-3-（3-二甲基氨丙基）-4,4-二甲基哌啶-2,6-二酮帕莫酸盐。

  公开号：

  WO2004017970A1

文献信息

• Process for the preparation of diethyl
  申请人：G. D. Searle & Co.

  公开号：US05220019A1

  公开（公告）日：1993-06-15

  Disclosed is a process for the preparation of 3-aryl-3-aminoalkyl-2,6-dioxohexahydropridines and particularly the compound 3-[3-(dimethylamino)propyl]3-(3 methoxyphenyl)-4, 4-dimethyl-2,6-piperidinedione, monohydrochloride, which is useful as an antidepressant. The process of the present invention comprises the condensation of a sterically hindered nitrile with a sterically hindered .alpha.,.beta.-unsaturated diester to produce a nitrile diester. These compounds can then undergo acid catalyzed cyclization and decarboalkoxylation in a one step process to provide the desired 3-aryl-3-aminoalkyl-2,6 -dioxohexahydropyridine.

  本发明揭示了一种制备3-芳基-3-氨基烷基-2,6-二酮六氢吡啶，特别是3-[3-(二甲氨基)丙基]3-(3-甲氧基苯基)-4,4-二甲基-2,6-哌啶二酮单盐酸盐的方法，该化合物可用作抗抑郁剂。本发明的方法包括将一个立体位阻的腈与一个立体位阻的α，β-不饱和二酯缩合以制备腈二酯。这些化合物随后可以在一步反应中经过酸催化的环化和脱羧烷氧基化反应，从而提供所需的3-芳基-3-氨基烷基-2,6-二酮六氢吡啶。
• Novel piperidin-2,6-dione disulphate salts and their use for the treatment of stress related affective disorders
  申请人：——

  公开号：US20040249159A1

  公开（公告）日：2004-12-09

  Novel bisulphate salts of certain 3-phenyl-3-dimethylaminoalkyl-4,4-dimethylpiperidin-2,6-diones and pharmacologically acceptable solvates thereof are devoid of the weight loss and hepatocyte changes in the rat which limited to marginally effective levels the permitted clinical doses of the corresponding hydrochlorides in the treatment or prophylaxis of stress-related affective disorders such as anxiety, depression, migraine and sleep apnoea. The preferred bisulphate salts are 3(3,5-dimethoxyphenyl)-3-(3-dimethylaminopropyl)-4,4-dimethylpiperidine-2,6-dione bisulphate and, especially, 3(3-methoxyphenyl)-3-(3-dimethylaminopropyl)-4,4-dimethylpiperidine-2,6-dione bisulphate.

  某些3-苯基-3-二甲氨基烷基-4,4-二甲基哌啶-2,6-二酮的新型双硫酸盐及其药学可接受的溶剂化合物不会出现大鼠体重减轻和肝细胞变化，这种变化限制了相应盐酸盐在治疗或预防压力相关情感障碍（如焦虑、抑郁、偏头痛和睡眠呼吸暂停）中允许的临床剂量的有效水平。首选的双硫酸盐为3（3,5-二甲氧基苯基）-3-（3-二甲基氨基丙基）-4,4-二甲基哌啶-2,6-二酮双硫酸盐，尤其是3（3-甲氧基苯基）-3-（3-二甲基氨基丙基）-4,4-二甲基哌啶-2,6-二酮双硫酸盐。
• Process for the preparation of
  申请人：G. D. Searle & Co.

  公开号：US05104990A1

  公开（公告）日：1992-04-14

  Disclosed is a process for the preparation of 3-aryl-3-aminoalkyl-2,6-dioxohexahydropridines and particularly the compounds 3-[3-(dimethylamino)propyl]-3-(3-methoxyphenyl)-4, 4-dimethyl-2,6-piperidinedione, monohydrochloride, which is useful as an antidepressant. the process of the present invention comprises the condensation of a sterically hindered nitrile with a sterically hindered .alpha., .beta.-unsaturated diester to produce a nitrile diester. These compounds can then undergo acid catalyzed cyclization and decarboalkoxylation in a one step process to provide the desired 3-aryl-3-aminoalkyl-2,6-dioxohexahydropyridine.

  本发明涉及一种制备3-芳基-3-氨基烷基-2,6-二酮己氢吡啶的方法，特别是化合物3-[3-(二甲氨基)丙基]-3-(3-甲氧基苯基)-4,4-二甲基-2,6-哌啶二酮单盐酸盐，该化合物可用作抗抑郁剂。本发明的方法包括通过难以立体位阻的腈与难以立体位阻的α，β-不饱和二酯缩合，制备腈二酯。这些化合物可以在一步反应中经过酸催化环化和去羧甲氧基化反应，提供所需的3-芳基-3-氨基烷基-2,6-二酮己氢吡啶。
• Piperidin-2,6-dione bisulphate salts and their use for the treatment of stress related affective disorders
  申请人：Prestwick Pharmaceuticals, Inc.

  公开号：US07189742B2

  公开（公告）日：2007-03-13

  Novel bisulphate salts of certain 3-phenyl-3-dimethylaminoalkyl-4,4-dimethylpiperidin-2,6-diones and pharmacologically acceptable solvates thereof are devoid of the weight loss and hepatocyte changes in the rat which limited to marginally effective levels the permitted clinical doses of the corresponding hydrochlorides in the treatment or prophylaxis of stress-related affective disorders such as anxiety, depression, migraine and sleep apnea. The preferred bisulphate salts are 3(3,5-dimethoxyphenyl)-3-(3-dimethylaminopropyl)-4,4-dimethylpiperidine-2,6-dione bisulphate and, especially, 3(3-methoxyphenyl)-3-(3-dimethylaminopropyl)-4,4-dimethylpiperidine-2,6-dione bisulphate.

  某些3-苯基-3-二甲基氨基烷基-4,4-二甲基哌啶-2,6-二酮及其药理学上可接受的溶剂化物的新型双硫酸盐，在治疗或预防与压力相关的情感障碍，如焦虑、抑郁、偏头痛和睡眠呼吸暂停等方面，不会出现大鼠体重减轻和肝细胞变化，这限制了相应盐酸的允许临床剂量的边缘有效水平。首选的双硫酸盐是3（3,5-二甲氧基苯基）-3-（3-二甲基氨丙基）-4,4-二甲基哌啶-2,6-二酮双硫酸盐，特别是3（3-甲氧基苯基）-3-（3-二甲基氨丙基）-4,4-二甲基哌啶-2,6-二酮双硫酸盐。
• Piperidin-2, 6-dione pamoate salts and their use for the treatment of affective disorders
  申请人：Wermuth Camille Georges

  公开号：US20090182012A1

  公开（公告）日：2009-07-16

  Novel pamoate salts of certain 3-phenyl-3-dimethylaminoalkyl-4,4-dimethylpiperidin-2,6-diones and pharmacologically acceptable solvates thereof are devoid of the weight loss and hepatocyte changes in the rat which limited to marginally effective levels the permitted clinical doses of the corresponding hydrochlorides in the treatment or prophylaxis of stress-related affective disorders such as anxiety, depression, migraine and sleep apnoea. The preferred pamoate salts are 3(3,5-dimethoxyphenyl)-3-(3-dimethylaminopropyl)-4,4-dimethylpiperidine-2,6-dione pamoate and, especially, 3(3-methoxyphenyl)-3-(3-dimethylaminopropyl)-4,4-dimethylpiperidine-2,6-dione pamoate.

  某些3-苯基-3-二甲基氨基烷基-4,4-二甲基哌啶-2,6-二酮的帕莫酸盐和药理学上可接受的溶剂化物，与相应的盐酸盐治疗或预防与压力有关的情感障碍，如焦虑、抑郁、偏头痛和睡眠呼吸暂停症，相比之下，不会出现大鼠的体重减轻和肝细胞改变，这些改变限制了相应的盐酸盐在治疗或预防这些疾病时的有效剂量。首选的帕莫酸盐是3（3,5-二甲氧基苯基）-3-（3-二甲基氨丙基）-4,4-二甲基哌啶-2,6-二酮帕莫酸盐，尤其是3（3-甲氧基苯基）-3-（3-二甲基氨丙基）-4,4-二甲基哌啶-2,6-二酮帕莫酸盐。