tert-butyl 3-((10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5-yllidene)-N-methylcarbamoyl)propylcarbamate | 1002331-77-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 二苯并环庚烯
• 英文名称: tert-butyl 3-((10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5-yllidene)-N-methylcarbamoyl)propylcarbamate
• 英文别名: tert-Butyl (4-{[3-(10,11-dihydro-5H-dibenzo[a,d][7]annulen-5-ylidene)propyl](methyl)amino}-4-oxobutyl)carbamate；tert-butyl N-[4-[methyl-[3-(2-tricyclo[9.4.0.03,8]pentadeca-1(15),3,5,7,11,13-hexaenylidene)propyl]amino]-4-oxobutyl]carbamate
• CAS: 1002331-77-2
• 化学式: C₂₈H₃₆N₂O₃
• 分子量: 448.605
• InChiKey: RCMUXKYLJXMBDM-UHFFFAOYSA-N

物化性质

• 沸点：
  613.4±55.0 °C(Predicted)
• 密度：
  1.123±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-((10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5-yllidene)-N-methylcarbamoyl)propylcarbamate 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 反应 4.0h， 生成 BL-1021盐酸盐
  参考文献：
  名称：

  γ-Aminobutyric Acid Amides of Nortriptyline and Fluoxetine Display Improved Pain Suppressing Activity

  摘要：

  The GABA amides of the antidepressants nortriptyline and fluoxetine, 1 and 2, were compared to their respective parent compounds in rodent models of pain. The amides significantly reduced early nociceptive and late inflammatory responses compared to nortriptyline or fluoxetine, where 1 exhibited overall better efficacy than 2. Amide 1 was most efficacious in lowering cytokine secretion, edema and hyperalgesia induced by formalin and lambda-carrageenan, respectively. Thus, 1 is a promising candidate for the treatment of pain.

  DOI：

  10.1021/jm900143u
• 作为产物：
  描述：

  N-BOC-GAMMA-氨基丁酸 、 去甲替林 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 以88%的产率得到tert-butyl 3-((10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5-yllidene)-N-methylcarbamoyl)propylcarbamate
  参考文献：
  名称：

  [EN] AN ACID ADDITION SALT OF A NORTRIPTYLINE-GABA CONJUGATE AND A PROCESS OF PREPARING SAME
  [FR] SEL D'ADDITION D'ACIDE D'UN CONJUGUÉ NORTRIPTYLINE-GABA ET SON PROCÉDÉ DE PRÉPARATION

  摘要：

  本文披露了一种诺曲普汀-GABA结合物的酸加盐，一种诺曲普汀-GABA结合物富马酸加盐的新结晶形式，以及制备上述物质的方法。还披露了上述形式的诺曲普汀-GABA结合物在治疗中枢神经系统疾病，特别是在疼痛治疗中的用途。此外，还披露了一种大规模制备诺曲普汀-GABA结合物的方法。

  公开号：

  WO2012038963A1

文献信息

• J. Med. Chem. 2009, 52, 3010-3017
  作者：

  DOI：——

  日期：——
• ACID ADDITION SALT OF A NORTRIPTYLINE-GABA CONJUGATE AND A PROCESS OF PREPARING SAME
  申请人：Nudelman Abraham

  公开号：US20130184347A1

  公开（公告）日：2013-07-18

  An acid addition salt of a nortriptyline-GABA conjugate, a novel crystalline form of a fumaric acid addition salt of a nortriptyline-GABA conjugate, and processes of preparing the forgoing are disclosed. Uses of the above-indicated forms of a nortriptyline-GABA conjugate in the treatment of CNS disorders, and in the treatment of pain in particular, are also disclosed. Further disclosed in a large-scale process of preparing a nortriptyline-GABA conjugate.
• US8916610B2
  申请人：——

  公开号：US8916610B2

  公开（公告）日：2014-12-23
• [EN] AN ACID ADDITION SALT OF A NORTRIPTYLINE-GABA CONJUGATE AND A PROCESS OF PREPARING SAME<br/>[FR] SEL D'ADDITION D'ACIDE D'UN CONJUGUÉ NORTRIPTYLINE-GABA ET SON PROCÉDÉ DE PRÉPARATION
  申请人：UNIV RAMOT

  公开号：WO2012038963A1

  公开（公告）日：2012-03-29

  An acid addition salt of a nortriptyline-GABA conjugate, a novel crystalline form of a fumaric acid addition salt of a nortriptyline-GABA conjugate, and processes of preparing the forgoing are disclosed. Uses of the above-indicated forms of a nortriptyline-GABA conjugate in the treatment of CNS disorders, and in the treatment of pain in particular, are also disclosed. Further disclosed in a large-scale process of preparing a nortriptyline-GABA conjugate.

  本文披露了一种诺曲普汀-GABA结合物的酸加盐，一种诺曲普汀-GABA结合物富马酸加盐的新结晶形式，以及制备上述物质的方法。还披露了上述形式的诺曲普汀-GABA结合物在治疗中枢神经系统疾病，特别是在疼痛治疗中的用途。此外，还披露了一种大规模制备诺曲普汀-GABA结合物的方法。
• γ-Aminobutyric Acid Amides of Nortriptyline and Fluoxetine Display Improved Pain Suppressing Activity
  作者：Ada Rephaeli、Irit Gil-Ad、Ana Aharoni、Igor Tarasenko、Nataly Tarasenko、Yona Geffen、Efrat Halbfinger、Yotam Nisemblat、Abraham Weizman、Abraham Nudelman

  DOI：10.1021/jm900143u

  日期：2009.5.14

  The GABA amides of the antidepressants nortriptyline and fluoxetine, 1 and 2, were compared to their respective parent compounds in rodent models of pain. The amides significantly reduced early nociceptive and late inflammatory responses compared to nortriptyline or fluoxetine, where 1 exhibited overall better efficacy than 2. Amide 1 was most efficacious in lowering cytokine secretion, edema and hyperalgesia induced by formalin and lambda-carrageenan, respectively. Thus, 1 is a promising candidate for the treatment of pain.