tert-butyl 4-[3-bromo-5-(2-methoxyethoxy)benzylidene]piperidine-1-carboxylate | 1176327-06-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-butyl 4-[3-bromo-5-(2-methoxyethoxy)benzylidene]piperidine-1-carboxylate
• 英文别名: tert-butyl 4-{[3-bromo-5-(2-methoxyethoxy)phenyl]methylidene}piperidine-1-carboxylate；Tert-butyl 4-[[3-bromo-5-(2-methoxyethoxy)phenyl]methylidene]piperidine-1-carboxylate
• CAS: 1176327-06-2
• 化学式: C₂₀H₂₈BrNO₄
• 分子量: 426.351
• InChiKey: LSQYZLRQWHXTKS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  48
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-[3-bromo-5-(2-methoxyethoxy)benzylidene]piperidine-1-carboxylate 在 5% rhodium-on-charcoal 氢气 作用下， 以 乙酸乙酯 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 26.0h， 以98%的产率得到tert-butyl 4-[3-bromo-5-(2-methoxyethoxy)benzyl]piperidine-1-carboxylate
  参考文献：
  名称：

  BENZYLPIPERIZINE COMPOUND

  摘要：

  揭示了一种由化学式（1）表示的苄基哌嗪化合物或其药学上可接受的盐，该化合物可用作药用剂，如抗抑郁剂。（在化学式（1）中，R1代表氢原子或甲基基团；R2是与亚甲基基团相对的p-或m-位置上结合的基团，代表结合在p-位置的氯原子、结合在p-位置的溴原子、结合在p-位置的甲基基团、结合在m-位置的氯原子或结合在m-位置的溴原子；X代表亚甲基或氧原子；n代表1到3的整数。）

  公开号：

  US20100113792A1
• 作为产物：
  描述：

  3-溴-5-(2-甲氧基乙氧基)苯甲醛 在 甲醇 、 sodium tetrahydroborate 、 三甲胺盐酸盐 、 potassium carbonate 、 三乙胺 、 lithium bromide 作用下， 以 四氢呋喃 、 异丙醇 、 甲苯 为溶剂， 反应 23.5h， 生成 tert-butyl 4-[3-bromo-5-(2-methoxyethoxy)benzylidene]piperidine-1-carboxylate
  参考文献：
  名称：

  Discovery of DSP-1053, a novel benzylpiperidine derivative with potent serotonin transporter inhibitory activity and partial 5-HT1A receptor agonistic activity

  摘要：

  We have previously shown that SMP-304, a serotonin uptake inhibitor with weak 5-HT1A partial agonistic activity, may act under high serotonin levels as a 5-HT1A antagonist that improves the onset of paroxetine in the rat swimming test. However, SMP-304 is mostly metabolized by CYP2D6, indicating limited efficacy among individuals and increased side effects. To reduce CYP2D6 metabolic contribution and enhance SERT/5-HT1A binding affinity, we carried out a series of substitutions at the bromine atom in the left part of the benzene ring of SMP-304 and replaced the right part of SMP-304 with a chroman4-one. This optimization work led to the identification of the antidepressant candidate DSP-1053 as a potent SERT inhibitor with partial 5-HT1A receptor agonistic activity. DSP-1053 showed low CYP2D6 metabolic contribution and a robust increase in serotonin levels in the rat frontal cortex. (c) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2018.02.008

文献信息

• BENZYLPIPERIZINE COMPOUND
  申请人：Toyoda Tomohiro

  公开号：US20100113792A1

  公开（公告）日：2010-05-06

  Disclosed is a benzylpiperizine compound represented by formula (1) or a pharmaceutically acceptable salt thereof, which is useful as a medicinal agent such as an antidepressant agent. (In the formula (1), R 1 represents a hydrogen atom or a methyl group; R 2 is a group bound in a p- or m-position relative to a methylene group and represents a chlorine atom bound in a p-position, a bromine atom bound in a p-position, a methyl group bound in a p-position, a chlorine atom bound in a m-position or a bromine atom bound to in a m-position; X represents a methylene or an oxygen atom; and n represents an integer of 1 to 3.)

  揭示了一种由化学式（1）表示的苄基哌嗪化合物或其药学上可接受的盐，该化合物可用作药用剂，如抗抑郁剂。（在化学式（1）中，R1代表氢原子或甲基基团；R2是与亚甲基基团相对的p-或m-位置上结合的基团，代表结合在p-位置的氯原子、结合在p-位置的溴原子、结合在p-位置的甲基基团、结合在m-位置的氯原子或结合在m-位置的溴原子；X代表亚甲基或氧原子；n代表1到3的整数。）
• US8063223B2
  申请人：——

  公开号：US8063223B2

  公开（公告）日：2011-11-22
• US8232405B2
  申请人：——

  公开号：US8232405B2

  公开（公告）日：2012-07-31
• US8557998B2
  申请人：——

  公开号：US8557998B2

  公开（公告）日：2013-10-15
• Discovery of DSP-1053, a novel benzylpiperidine derivative with potent serotonin transporter inhibitory activity and partial 5-HT1A receptor agonistic activity
  作者：Hidefumi Yoshinaga、Tomoaki Nishida、Izumi Sasaki、Taro Kato、Hitomi Oki、Kazuki Yabuuchi、Tomohiro Toyoda

  DOI：10.1016/j.bmc.2018.02.008

  日期：2018.5

  We have previously shown that SMP-304, a serotonin uptake inhibitor with weak 5-HT1A partial agonistic activity, may act under high serotonin levels as a 5-HT1A antagonist that improves the onset of paroxetine in the rat swimming test. However, SMP-304 is mostly metabolized by CYP2D6, indicating limited efficacy among individuals and increased side effects. To reduce CYP2D6 metabolic contribution and enhance SERT/5-HT1A binding affinity, we carried out a series of substitutions at the bromine atom in the left part of the benzene ring of SMP-304 and replaced the right part of SMP-304 with a chroman4-one. This optimization work led to the identification of the antidepressant candidate DSP-1053 as a potent SERT inhibitor with partial 5-HT1A receptor agonistic activity. DSP-1053 showed low CYP2D6 metabolic contribution and a robust increase in serotonin levels in the rat frontal cortex. (c) 2018 Elsevier Ltd. All rights reserved.