4-(2-phenylethyl)piperidine-1,4-dicarboxylic acid 4-ethyl 1-tert-butyl diester | 152830-59-6

• 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: 4-(2-phenylethyl)piperidine-1,4-dicarboxylic acid 4-ethyl 1-tert-butyl diester
• 英文别名: 1-(tert-butyl) 4-ethyl 4-phenethylpiperidine-1,4-dicarboxylate；1-O-tert-butyl 4-O-ethyl 4-(2-phenylethyl)piperidine-1,4-dicarboxylate
• CAS: 152830-59-6
• 化学式: C₂₁H₃₁NO₄
• 分子量: 361.481
• InChiKey: BGPXTFAKEGFVAZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(2-phenylethyl)piperidine-1,4-dicarboxylic acid 4-ethyl 1-tert-butyl diester 在 sodium hydroxide 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 56.0h， 生成 1-环己基甲基-4-苯乙基-哌啶-4-羧酸
  参考文献：
  名称：

  Piperidinyltetralin .sigma. Ligands

  摘要：

  sigma receptor ligands have been proposed to be potential antipsychotic drugs based on their activity profile in animal behavioral models and their indirect modulation of dopaminergic function. Compound 15 (DuP 734) is a combined antagonist of sigma-1 and serotonin 5HT(2) receptors, which has been entered into phase I clinical trials as a potential antipsychotic drug. Tetralins 1 and 2 were prepared to determine whether restriction of the conformation of 15 and its analogs may lead to differences in binding selectivity or in vivo profile. The syntheses and the structure-activity relationships of these compounds are reported herein. A reduced derivative, 14, had high affinity for sigma-1 and serotonin 5HT(2) receptors as well as excellent oral activity in some animal antipsychotic models. Furthermore, compound 14 failed to cause catalepsy in the rat up to 90 mg/kg (po).

  DOI：

  10.1021/jm00029a008
• 作为产物：
  描述：

  哌啶-4-甲酸乙酯 在 sodium hydroxide 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 45.0h， 生成 4-(2-phenylethyl)piperidine-1,4-dicarboxylic acid 4-ethyl 1-tert-butyl diester
  参考文献：
  名称：

  Piperidinyltetralin .sigma. Ligands

  摘要：

  sigma receptor ligands have been proposed to be potential antipsychotic drugs based on their activity profile in animal behavioral models and their indirect modulation of dopaminergic function. Compound 15 (DuP 734) is a combined antagonist of sigma-1 and serotonin 5HT(2) receptors, which has been entered into phase I clinical trials as a potential antipsychotic drug. Tetralins 1 and 2 were prepared to determine whether restriction of the conformation of 15 and its analogs may lead to differences in binding selectivity or in vivo profile. The syntheses and the structure-activity relationships of these compounds are reported herein. A reduced derivative, 14, had high affinity for sigma-1 and serotonin 5HT(2) receptors as well as excellent oral activity in some animal antipsychotic models. Furthermore, compound 14 failed to cause catalepsy in the rat up to 90 mg/kg (po).

  DOI：

  10.1021/jm00029a008

文献信息

• POLYCYCLIC AMINES AS OPIOID RECEPTOR MODULATORS
  申请人：WANG XIAODONG

  公开号：US20180258065A1

  公开（公告）日：2018-09-13

  The present invention provides a genus of polycyclic amines that are useful as opioid receptor modulators. The compounds of the invention are useful in both therapeutic and diagnostic methods, including for treating pain, neurological disorders, cardiac disorders, bowel disorders, drug and alcohol addiction, drug overdose, urinary disorders, respiratory disorders, sexual dysfunction, psoriasis, graft rejection or cancer.

  本发明提供了一类多环胺类化合物，可用作阿片受体调节剂。该发明的化合物可用于治疗和诊断方法，包括治疗疼痛、神经系统疾病、心脏疾病、肠道疾病、药物和酒精成瘾、药物过量、泌尿系统疾病、呼吸系统疾病、性功能障碍、银屑病、移植排斥或癌症。
• Polycyclic amines as opioid receptor modulators
  申请人：Wang Xiaodong

  公开号：US10676456B2

  公开（公告）日：2020-06-09

  The present invention provides a genus of polycyclic amines that are useful as opioid receptor modulators. The compounds of the invention are useful in both therapeutic and diagnostic methods, including for treating pain, neurological disorders, cardiac disorders, bowel disorders, drug and alcohol addiction, drug overdose, urinary disorders, respiratory disorders, sexual dysfunction, psoriasis, graft rejection or cancer.

  本发明提供了一种可用作阿片受体调节剂的多环胺属化合物。本发明的化合物可用于治疗和诊断方法，包括治疗疼痛、神经系统疾病、心脏疾病、肠道疾病、药物和酒精成瘾、药物过量、泌尿系统疾病、呼吸系统疾病、性功能障碍、牛皮癣、移植物排斥或癌症。
• 10.1248/cpb.c24-00188
  作者：Watanabe, Ayaka、Yamada, Shuma、Yoshida, Haruka、Inagaki, Miku、Atsumi, Nao、Matsushima, Aoba、Takahashi, Naoki、Ishibashi, Naoto、Ogino, Takumi、Someya, Ryoto、Taguchi, Ai、Kagaya, Ryo、Ashizawa, Karin、Mendori, Hinako、Karasawa, Yusuke、Ohshima, Kaori、Yokoyama, Akinobu、Nonaka, Miki、Miyano, Kanako、Karaki, Fumika、Hirayama, Shigeto、Itoh, Kennosuke、Uezono, Yasuhito、Fujii, Hideaki

  DOI：10.1248/cpb.c24-00188

  日期：——

  the µ opioid receptor (MOR), a heterodimer between the MOR and the δ opioid receptor (DOR) has emerged as another target to develop safer analgesics. Although some heterodimer-preferring agonists have been reported so far, it is still difficult to activate the MOR/DOR heterodimer selectively in the presence of MOR or DOR monomers/homodimers. To gain insights to develop selective agonists for MOR/DOR

  尽管阿片类镇痛药对于治疗疼痛是不可或缺的，但这些药物伴随着危及生命的副作用。虽然临床相关的阿片类药物以 µ 阿片受体 (MOR) 为靶点，但 MOR 和 δ 阿片受体 (DOR) 之间的异二聚体已成为开发更安全镇痛药的另一个靶点。尽管迄今为止已经报道了一些异二聚体偏好的激动剂，但在MOR或DOR单体/同二聚体存在的情况下选择性激活MOR/DOR异二聚体仍然很困难。为了获得开发 MOR/DOR 选择性激动剂的见解，本文中我们制备了 CYM51010（已报道的异二聚体偏好激动剂之一）的类似物，并收集了结构-活性关系信息。我们发现，异二聚体的活性需要乙氧基羰基，尽管该基团可以被大小相似的官能团（例如乙氧基羰基）取代。对于乙酰氨基苯基来说，活性所必需的不是取代基的类型，而是位于特定位置(对位)的取代基。改变乙酰氨基苯基和哌啶部分之间的连接长度也会对活性产生有害影响。另一方面，乙酰氨基被三氟乙酰氨基
• [EN] POLYCYCLIC AMINES AS OPIOID RECEPTOR MODULATORS<br/>[FR] AMINES POLYCYCLIQUES UTILISÉES COMME MODULATEURS DES RÉCEPTEURS OPIOÏDES
  申请人：WANG XIAODONG

  公开号：WO2018169818A1

  公开（公告）日：2018-09-20

  The present invention provides a genus of polycyclic amines that are useful as opioid receptor modulators. The compounds of the invention are useful in both therapeutic and diagnostic methods, including for treating pain, neurological disorders, cardiac disorders, bowel disorders, drug and alcohol addiction, drug overdose, urinary disorders, respiratory disorders, sexual dysfunction, psoriasis, graft rejection or cancer.
• Piperidinyltetralin .sigma. Ligands
  作者：Paul J. Gilligan、Ahmed A. Kergaye、Bryan M. Lewis、John F. McElroy

  DOI：10.1021/jm00029a008

  日期：1994.2

  sigma receptor ligands have been proposed to be potential antipsychotic drugs based on their activity profile in animal behavioral models and their indirect modulation of dopaminergic function. Compound 15 (DuP 734) is a combined antagonist of sigma-1 and serotonin 5HT(2) receptors, which has been entered into phase I clinical trials as a potential antipsychotic drug. Tetralins 1 and 2 were prepared to determine whether restriction of the conformation of 15 and its analogs may lead to differences in binding selectivity or in vivo profile. The syntheses and the structure-activity relationships of these compounds are reported herein. A reduced derivative, 14, had high affinity for sigma-1 and serotonin 5HT(2) receptors as well as excellent oral activity in some animal antipsychotic models. Furthermore, compound 14 failed to cause catalepsy in the rat up to 90 mg/kg (po).