2-<<4-<2-(tert-butoxycarbonyl)etyl>phenethyl>amino>-2',3'-O-isopropylideneadenosine-5'-N-ethylcarboxamide | 120225-76-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 2-<<4-<2-(tert-butoxycarbonyl)etyl>phenethyl>amino>-2',3'-O-isopropylideneadenosine-5'-N-ethylcarboxamide
• 英文别名: 2-({4-[2-(tert-butoxycarbonyl)etyl]phenethyl}amino)-2',3'-O-isopropylideneadenosine-5'-N-ethylcarboxamide；tert-butyl 3-(4-(2-(6-amino-9-((3aR,4R,6S,6aS)-6-(ethylcarbamoyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-9H-purin-2-ylamino)ethyl)phenyl)propanoate；tert-butyl 3-[4-[2-[[9-[(3aR,4R,6S,6aS)-6-(ethylcarbamoyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-6-aminopurin-2-yl]amino]ethyl]phenyl]propanoate
• CAS: 120225-76-5
• 化学式: C₃₀H₄₁N₇O₆
• 分子量: 595.699
• InChiKey: HTABKEQHHQHYFD-QSGNWFJVSA-N

物化性质

• 熔点：
  182-186°C
• 溶解度：
  可溶于DMSO、乙酸乙酯、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  43
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  165
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  2-<<4-<2-(tert-butoxycarbonyl)etyl>phenethyl>amino>-2',3'-O-isopropylideneadenosine-5'-N-ethylcarboxamide 在 盐酸 、 乙醇 、 methyloxirane 作用下， 反应 4.0h， 生成 2-<<4-(2-carbomethoxyetyl)phenethyl>amino>adenosine-5'-N-ethylcarboxamide hydrochloride
  参考文献：
  名称：

  2-(Arylalkylamino)adenosin-5'-uronamides: a new class of highly selective adenosine A2 receptor ligands

  摘要：

  The synthesis and receptor-binding profiles at adenosine receptor subtypes for a series of 2-(arylalkylamino)-adenosin-5'-uronamides is described. Halogenated 2-phenethylamino analogues such as 3e show greater than 200-fold selectivity for the A2 receptor subtype on the basis of rat brain receptor binding. The general structure-activity relationship of this series of compounds is discussed both in terms of potency at A2 receptors as well as receptor subtype selectivity. It is possible to introduce a hydrophilic carboxyalkyl substituent to this series such as in CGS 21680A (3h) and still retain good potency and selectivity for A2 receptors. In addition, functional data in a perfused working rat heart model shows that these compounds possess full agonist properties at A2 receptors with 3h having a greater than 1500-fold separation between A2 (coronary vasodilatory) and A1 (negative chronotropic) receptor mediated events.

  DOI：

  10.1021/jm00169a015
• 作为产物：
  描述：

  2-氯腺嘌呤核苷 在 氢氧化钾 、 potassium permanganate 、 氯化亚砜 、 camphor-10-sulfonic acid 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 94.0h， 生成 2-<<4-<2-(tert-butoxycarbonyl)etyl>phenethyl>amino>-2',3'-O-isopropylideneadenosine-5'-N-ethylcarboxamide
  参考文献：
  名称：

  2-(Arylalkylamino)adenosin-5'-uronamides: a new class of highly selective adenosine A2 receptor ligands

  摘要：

  The synthesis and receptor-binding profiles at adenosine receptor subtypes for a series of 2-(arylalkylamino)-adenosin-5'-uronamides is described. Halogenated 2-phenethylamino analogues such as 3e show greater than 200-fold selectivity for the A2 receptor subtype on the basis of rat brain receptor binding. The general structure-activity relationship of this series of compounds is discussed both in terms of potency at A2 receptors as well as receptor subtype selectivity. It is possible to introduce a hydrophilic carboxyalkyl substituent to this series such as in CGS 21680A (3h) and still retain good potency and selectivity for A2 receptors. In addition, functional data in a perfused working rat heart model shows that these compounds possess full agonist properties at A2 receptors with 3h having a greater than 1500-fold separation between A2 (coronary vasodilatory) and A1 (negative chronotropic) receptor mediated events.

  DOI：

  10.1021/jm00169a015

文献信息

• An Fc Domain Protein–Small Molecule Conjugate as an Enhanced Immunomodulator
  作者：Meng-Jung Chiang、Marc A. Holbert、Jay H. Kalin、Young-Hoon Ahn、John Giddens、Mohammed N. Amin、Martin S. Taylor、Samuel L. Collins、Yee Chan-Li、Adam Waickman、Po-Yuan Hsiao、David Bolduc、Daniel J. Leahy、Maureen R. Horton、Lai-Xi Wang、Jonathan D. Powell、Philip A. Cole

  DOI：10.1021/ja5006674

  日期：2014.3.5

  Proteins as well as small molecules have demonstrated success as therapeutic agents, but their pharmacologic properties sometimes fall short against particular drug targets. Although the adenosine 2a receptor (A(2A)R) has been identified as a promising target for immunotherapy, small molecule A(2A)R agonists have suffered from short pharmacokinetic half-lives and the potential for toxicity by modulating nonimmune pathways. To overcome these limitations, we have tethered the AR agonist CGS-21680 to the immunoglobulin Fc domain using expressed protein ligation with Sf9 cell secreted protein. The protein small molecule conjugate Fc-CGS retained potent Fc receptor and A(2A)R interactions and showed superior properties as a therapeutic for the treatment of a mouse model of autoimmune pneumonitis. This approach may provide a general strategy for optimizing small molecule therapeutics.
• HUTCHISON, ALAN J.;WILLIAMS, MICHAEL;JESUS, REYNALDA DE;RINA, YOKOYAMA;OE+, J. MED. CHEM., 33,(1990) N, C. 1919-1924
  作者：HUTCHISON, ALAN J.、WILLIAMS, MICHAEL、JESUS, REYNALDA DE、RINA, YOKOYAMA、OE+

  DOI：——

  日期：——
• 2-(Arylalkylamino)adenosin-5'-uronamides: a new class of highly selective adenosine A2 receptor ligands
  作者：Alan J. Hutchison、Michael Williams、Reynalda De Jesus、Rina Yokoyama、Howard H. Oei、Geetha R. Ghai、Randy L. Webb、Harry C. Zoganas、George A. Stone、Michael F. Jarvis

  DOI：10.1021/jm00169a015

  日期：1990.7

  The synthesis and receptor-binding profiles at adenosine receptor subtypes for a series of 2-(arylalkylamino)-adenosin-5'-uronamides is described. Halogenated 2-phenethylamino analogues such as 3e show greater than 200-fold selectivity for the A2 receptor subtype on the basis of rat brain receptor binding. The general structure-activity relationship of this series of compounds is discussed both in terms of potency at A2 receptors as well as receptor subtype selectivity. It is possible to introduce a hydrophilic carboxyalkyl substituent to this series such as in CGS 21680A (3h) and still retain good potency and selectivity for A2 receptors. In addition, functional data in a perfused working rat heart model shows that these compounds possess full agonist properties at A2 receptors with 3h having a greater than 1500-fold separation between A2 (coronary vasodilatory) and A1 (negative chronotropic) receptor mediated events.