1-(2-aminoethyl)-3,4-dihydro-2(1H)-isoquinolinecarboxylic acid-1,1-dimethylethyl ester | 222022-64-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: 1-(2-aminoethyl)-3,4-dihydro-2(1H)-isoquinolinecarboxylic acid-1,1-dimethylethyl ester
• 英文别名: 1,1-dimethylethyl 1-(2-aminoethyl)-3,4-dihydro-2(1 H)-isoquinolinecarboxylate；Tert-butyl 1-(2-aminoethyl)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate；tert-butyl 1-(2-aminoethyl)-3,4-dihydro-1H-isoquinoline-2-carboxylate
• CAS: 222022-64-2
• 化学式: C₁₆H₂₄N₂O₂
• 分子量: 276.379
• InChiKey: PJPADIHDUZOYIQ-UHFFFAOYSA-N

物化性质

• 沸点：
  397.3±35.0 °C(Predicted)
• 密度：
  1.080±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2-aminoethyl)-3,4-dihydro-2(1H)-isoquinolinecarboxylic acid-1,1-dimethylethyl ester 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 19.25h， 生成
  参考文献：
  名称：

  Parallel synthesis and biological activity of a new class of high affinity and selective δ-opioid ligand

  摘要：

  A considerable number of research papers describing the synthesis and testing of the delta opioid receptor (DOR) ligands, SNC-80 and TAN-67, and analogues of these two compounds, have been published in recent years. However, there have been few reports of the discovery of completely new structural classes of selective DOR ligand. By optimising a hit compound identified by high throughput screening, a new series of tetrahydroisoquinoline sulphonamide-based delta opioid ligands was discovered. The main challenge in this series was to simultaneously improve both affinity and physico chemical properties, notably aqueous solubility. The most active ligand had an affinity (IC50) of 6 nM for the cloned human DOR, representing a 15-fold improvement relative to the original hit I (IC50 98 nM). Compounds from this new series show good selectivity for the DOR over mu and K opioid receptors. However the most active and selective compounds had poor aqueous solubility. Improved aqueous solubility was obtained by replacing the phthalimide group in I by basic groups, allowing the synthesis of salt forms. A series of compounds with improved affinity and solubility relative to I was identified and these compounds showed activity in an in vivo model of antinociception, the formalin paw test, In the case of compound 19, this analgesic activity was shown to be mediated primarily via a DOR mechanism. The most active compound in vivo, 46, showed superior potency in this test compared to the reference DOR ligand, TAN-67 and similar potency to morphine (68% and 58% inhibition in Phases 1 and 2, respectively, at a dose of 10 mmol/kg i.v.). (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00017-7
• 作为产物：
  描述：

  2-[2-(1,2,3,4-Tetrahydro-isoquinolin-1-yl)-ethyl]-isoindole-1,3-dione 在 碳酸氢钠 、 一水合肼 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 19.0h， 生成 1-(2-aminoethyl)-3,4-dihydro-2(1H)-isoquinolinecarboxylic acid-1,1-dimethylethyl ester
  参考文献：
  名称：

  Parallel synthesis and biological activity of a new class of high affinity and selective δ-opioid ligand

  摘要：

  A considerable number of research papers describing the synthesis and testing of the delta opioid receptor (DOR) ligands, SNC-80 and TAN-67, and analogues of these two compounds, have been published in recent years. However, there have been few reports of the discovery of completely new structural classes of selective DOR ligand. By optimising a hit compound identified by high throughput screening, a new series of tetrahydroisoquinoline sulphonamide-based delta opioid ligands was discovered. The main challenge in this series was to simultaneously improve both affinity and physico chemical properties, notably aqueous solubility. The most active ligand had an affinity (IC50) of 6 nM for the cloned human DOR, representing a 15-fold improvement relative to the original hit I (IC50 98 nM). Compounds from this new series show good selectivity for the DOR over mu and K opioid receptors. However the most active and selective compounds had poor aqueous solubility. Improved aqueous solubility was obtained by replacing the phthalimide group in I by basic groups, allowing the synthesis of salt forms. A series of compounds with improved affinity and solubility relative to I was identified and these compounds showed activity in an in vivo model of antinociception, the formalin paw test, In the case of compound 19, this analgesic activity was shown to be mediated primarily via a DOR mechanism. The most active compound in vivo, 46, showed superior potency in this test compared to the reference DOR ligand, TAN-67 and similar potency to morphine (68% and 58% inhibition in Phases 1 and 2, respectively, at a dose of 10 mmol/kg i.v.). (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00017-7

文献信息

• PROTEASE INHIBITORS AND METHODS OF USING SAME
  申请人：[en]VARIATIONAL AI INC.

  公开号：WO2024130411A1

  公开（公告）日：2024-06-27

  Inhibitors of the SARS-CoV-2 Mproprotease and methods of their use in treating a coronavirus infection in a subject are provided. The inhibitors may have the general structure (I) :
• Parallel synthesis and biological activity of a new class of high affinity and selective δ-opioid ligand
  作者：D.R. Barn、W.L. Caulfield、J. Cottney、K. McGurk、J.R. Morphy、Z. Rankovic、B. Roberts

  DOI：10.1016/s0968-0896(01)00017-7

  日期：2001.10

  A considerable number of research papers describing the synthesis and testing of the delta opioid receptor (DOR) ligands, SNC-80 and TAN-67, and analogues of these two compounds, have been published in recent years. However, there have been few reports of the discovery of completely new structural classes of selective DOR ligand. By optimising a hit compound identified by high throughput screening, a new series of tetrahydroisoquinoline sulphonamide-based delta opioid ligands was discovered. The main challenge in this series was to simultaneously improve both affinity and physico chemical properties, notably aqueous solubility. The most active ligand had an affinity (IC50) of 6 nM for the cloned human DOR, representing a 15-fold improvement relative to the original hit I (IC50 98 nM). Compounds from this new series show good selectivity for the DOR over mu and K opioid receptors. However the most active and selective compounds had poor aqueous solubility. Improved aqueous solubility was obtained by replacing the phthalimide group in I by basic groups, allowing the synthesis of salt forms. A series of compounds with improved affinity and solubility relative to I was identified and these compounds showed activity in an in vivo model of antinociception, the formalin paw test, In the case of compound 19, this analgesic activity was shown to be mediated primarily via a DOR mechanism. The most active compound in vivo, 46, showed superior potency in this test compared to the reference DOR ligand, TAN-67 and similar potency to morphine (68% and 58% inhibition in Phases 1 and 2, respectively, at a dose of 10 mmol/kg i.v.). (C) 2001 Elsevier Science Ltd. All rights reserved.