4,4-diphenyl-1-butylamine hydrochloride

• 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: 4,4-diphenyl-1-butylamine hydrochloride
• 英文别名: 4,4-diphenylbutan-1-amine hydrochloride；4,4-diphenylbutylamine hydrochloride；4,4-Diphenylbutylamine hydrochloride；4,4-diphenylbutan-1-amine;hydrochloride
• 化学式: C₁₆H₁₉N*ClH
• 分子量: 261.794
• InChiKey: MQFLILPZNNSOGK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.98
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  26
• 氢给体数：
  2
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  4,4-diphenyl-1-butylamine hydrochloride 在 3 A molecular sieve 、 氢溴酸 、 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 17.0h， 生成 (RS)-4-N-(4,4-diphenylbut-1-yl)amino-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol hydrobromide
  参考文献：
  名称：

  Selective inhibitors of GABA uptake: synthesis and molecular pharmacology of 4-N-methylamino-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol analogues

  摘要：

  A series of lipophilic diaromatic derivatives of the glia-selective GABA uptake inhibitor (R)-4-amino-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol [(R)-exo-THPO, 4] were synthesized via reductive amination of 3-ethoxy-4,5,6,7-tetrahydrobenzo[d]isoxazol-4-one (9) or via N-alkylation of O-alkylatedracemic 4. The effects of the target compounds on GABA uptake mechanisms in vitro were measured using a rat brain synaptosomal preparation or primary cultures of mouse cortical neurons and glia cells (astrocytes), as well as HEK cells transfected with cloned mouse GABA transporter subtypes (GAT1-4). The activity against isoniazid-induced convulsions in mice after subcutaneous administration of the compounds was determined. All of the compounds were potent inhibitors of synaptosomal uptake the most potent compound being (RS)-4-[N-(1,1-diphenylbut-1-4-en-yl)amino]-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol (17a, IC50 = 0.14 muM). The majority of the compounds showed a weak preference for glial, as compared to neuronal, GABA uptake. The highest degree of selectivity was 10-fold corresponding to the glia selectivity of (R)-N-methyl-exo-THPO (5). All derivatives showed a preference for the GAT1 transporter, as compared with GAT2-4, with the exception of (RS)-4-[N-[1,1-bis(3-methyl-2-thienyl)but-1-en-4-yl]-N-methylamino]-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol (28d), which quite surprisingly turned out to be more potent than GABA at both GAT1 and GAT2 subtypes. The GAT1 activity was shown to reside in (R)-28d whereas (R)-28d and (S)-28d contributed equally to GAT2 activity. This makes (S)-28d a GAT2 selective compound, and (R)-28d equally effective in inhibition of GAT1 and GAT2 mediated GABA transport. All compounds tested were effective as anticonvulsant reflecting that these compounds have blood-brain barrier permeating ability. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.10.029
• 作为产物：
  描述：

  2,2-diphenylpyrrolidine 在 三(五氟苯基)硼烷 、 苯硅烷 、 盐酸 作用下， 以 乙醚 为溶剂， 以96 %的产率得到4,4-diphenyl-1-butylamine hydrochloride
  参考文献：
  名称：

  B(C6F5)3-催化环胺与氢硅烷的区域选择性开环

  摘要：

  强硼路易斯酸B(C 6 F 5 ) 3与苯基硅烷结合，能够分别区域选择性地裂解环状仲胺和叔胺中两个或三个碳氮键中的一个。这种胺解构扩展到大的饱和含氮杂环，并且官能团耐受性良好。

  DOI：

  10.1002/chem.202203721

文献信息

• 4-aminotetrahydrobenzisoxazole or -isothiazole compounds
  申请人：H. Lundbeck A/S

  公开号：US05998613A1

  公开（公告）日：1999-12-07

  The present invention relates to novel 4-aminotetrahydrobenzisoxazoles or 4-aminotetrahydrobenziothiazoles having gamma-aminobutanoic acid (GABA)-uptake inhibiting activity and thus useful in the treatment of analgesia, psychosis, convulsions, anxiety, epileptic disorders or muscular and movement disorders, such as spastic disorders or symptoms in Huntington's disease or Parkinson disease.

  本发明涉及具有γ-氨基丁酸（GABA）摄取抑制活性的新型4-氨基四氢苯并异噁唑或4-氨基四氢苯并噻唑，因此在治疗疼痛、精神病、抽搐、焦虑、癫痫性疾病或肌肉和运动障碍方面具有用处，如在亨廷顿病或帕金森病中的痉挛障碍或症状。
• WO2006/62224
  申请人：——

  公开号：——

  公开（公告）日：——
• Selective inhibitors of GABA uptake: synthesis and molecular pharmacology of 4-N-methylamino-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol analogues
  作者：Rasmus P. Clausen、Ejner K. Moltzen、Jens Perregaard、Sibylle M. Lenz、Connie Sanchez、Erik Falch、Bente Frølund、Tina Bolvig、Alan Sarup、Orla M. Larsson、Arne Schousboe、Povl Krogsgaard-Larsen

  DOI：10.1016/j.bmc.2004.10.029

  日期：2005.2

  A series of lipophilic diaromatic derivatives of the glia-selective GABA uptake inhibitor (R)-4-amino-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol [(R)-exo-THPO, 4] were synthesized via reductive amination of 3-ethoxy-4,5,6,7-tetrahydrobenzo[d]isoxazol-4-one (9) or via N-alkylation of O-alkylatedracemic 4. The effects of the target compounds on GABA uptake mechanisms in vitro were measured using a rat brain synaptosomal preparation or primary cultures of mouse cortical neurons and glia cells (astrocytes), as well as HEK cells transfected with cloned mouse GABA transporter subtypes (GAT1-4). The activity against isoniazid-induced convulsions in mice after subcutaneous administration of the compounds was determined. All of the compounds were potent inhibitors of synaptosomal uptake the most potent compound being (RS)-4-[N-(1,1-diphenylbut-1-4-en-yl)amino]-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol (17a, IC50 = 0.14 muM). The majority of the compounds showed a weak preference for glial, as compared to neuronal, GABA uptake. The highest degree of selectivity was 10-fold corresponding to the glia selectivity of (R)-N-methyl-exo-THPO (5). All derivatives showed a preference for the GAT1 transporter, as compared with GAT2-4, with the exception of (RS)-4-[N-[1,1-bis(3-methyl-2-thienyl)but-1-en-4-yl]-N-methylamino]-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol (28d), which quite surprisingly turned out to be more potent than GABA at both GAT1 and GAT2 subtypes. The GAT1 activity was shown to reside in (R)-28d whereas (R)-28d and (S)-28d contributed equally to GAT2 activity. This makes (S)-28d a GAT2 selective compound, and (R)-28d equally effective in inhibition of GAT1 and GAT2 mediated GABA transport. All compounds tested were effective as anticonvulsant reflecting that these compounds have blood-brain barrier permeating ability. (C) 2004 Elsevier Ltd. All rights reserved.
• B(C ₆ F ₅ ) ₃ ‐Catalyzed Regioselective Ring Opening of Cyclic Amines with Hydrosilanes
  作者：Yi Peng、Martin Oestreich

  DOI：10.1002/chem.202203721

  日期：2023.3

  The strong boron Lewis acid B(C6F5)3 in combination with phenylsilane enables the regioselective cleavage of one out of two or three carbon–nitrogen bonds in cyclic secondary and tertiary amines, respectively. This amine deconstruction extends to large saturated nitrogen-containing heterocycles, and the functional-group tolerance is good.

  强硼路易斯酸B(C 6 F 5 ) 3与苯基硅烷结合，能够分别区域选择性地裂解环状仲胺和叔胺中两个或三个碳氮键中的一个。这种胺解构扩展到大的饱和含氮杂环，并且官能团耐受性良好。