[[(2R,3S,4R,5R)-5-(6-amino-8-phenylpurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2R,3S,4R,5R)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate;N,N-diethylethanamine | 1018828-99-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - （5'->5'）-二核苷酸
• 英文名称: [[(2R,3S,4R,5R)-5-(6-amino-8-phenylpurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2R,3S,4R,5R)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate;N,N-diethylethanamine
• CAS: 1018828-99-3
• 化学式: C₆H₁₅N*C₂₇H₃₁N₇O₁₄P₂
• 分子量: 840.721
• InChiKey: WSYJBYUKYAOZIK-AZKKDFOLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.63
• 重原子数：
  57
• 可旋转键数：
  15
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  324
• 氢给体数：
  7
• 氢受体数：
  19

反应信息

• 作为反应物：
  描述：

  [[(2R,3S,4R,5R)-5-(6-amino-8-phenylpurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2R,3S,4R,5R)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate;N,N-diethylethanamine 在 Aplysia cyclase 、 HEPES buffer 作用下， 反应 1.0h， 生成 (2R,3R,4S,5R,13R,14S,15R,16R)-24-amino-10-hydroxy-8-oxido-8,10-dioxo-18-phenyl-7,9,11,25,26-pentaoxa-17,19,22-triaza-1-azonia-8lambda5,10lambda5-diphosphapentacyclo[18.3.1.12,5.113,16.017,21]hexacosa-1(24),18,20,22-tetraene-3,4,14,15-tetrol;N,N-diethylethanamine
  参考文献：
  名称：

  2′-Deoxy Cyclic Adenosine 5′-Diphosphate Ribose Derivatives: Importance of the 2′-Hydroxyl Motif for the Antagonistic Activity of 8-Substituted cADPR Derivatives

  摘要：

  The structural features needed for antagonism at the cyclic ADP-ribose (cADPR) receptor are unclear. Chemoenzymatic syntheses of novel 8-substituted 2'-deoxy-cADPR analogues, including 8-bromo-2'-deoxy-cADPR 7, 8-amino-2'-deoxy-cADPR 8, 8-O-methyl-2'-deoxy-cADPR 9, 8-phenyl-2'-deoxy-cADPR 10 and its ribose counterpart 8-phenyl-cADPR 5 are reported, including improved syntheses of established antagonists 8-amino-cADPR 2 and 8-bromo-cADPR 3. Aplysia californica ADP-ribosyl cyclase tolerates even the bulky 8-phenyl-nicotinamide adenine 5'-dinucleotide as a substrate. Structure-activity relationships of 8-substituted cADPR analogues in both Jurkat T-lymphocytes and sea urchin egg homogenate (SUH) were investigated. 2'-OH Deletion decreased antagonistic activity (at least for the 8-amino series), showing it to be an important motif. Some 8-substituted 2'-deoxy analogues showed agonist activity at higher concentrations, among which 8-bromo-2'-deoxy-cADPR 7 was, unexpectedly, a weak but almost full agonist in SUH and was membrane-permeant in whole eggs. Classical antagonists 2 and 3 also showed. previously unobserved agonist activity at higher concentrations in both systems. The 2'-OH group, without effect on the Ca(2+)-mobilizing ability of cADPR itself, is an important motif for the antagonistic activities of 8-substituted cADPR analogues.

  DOI：

  10.1021/jm7010386
• 作为产物：
  描述：

  β-烟酰胺腺嘌呤二核苷酸 在 溴 、 potassium carbonate 、 tris(4,6-dimethyl-3-sulfonatophenyl)phosphine trisodium salt hydrate 作用下， 以 水 为溶剂， 反应 2.17h， 生成 [[(2R,3S,4R,5R)-5-(6-amino-8-phenylpurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2R,3S,4R,5R)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate;N,N-diethylethanamine
  参考文献：
  名称：

  分两步合成新型无处不在的辅因子烟酰胺腺嘌呤二核苷酸（NAD）的生物活性衍生物

  摘要：

  我们报告了设计和简洁的合成，从市售材料中分两步合成了酶辅因子烟酰胺腺嘌呤二核苷酸（NAD）的新型生物活性衍生物。新的合成二核苷酸充当sirtuin（SIRT）抑制剂，并且相对于SIRT1表现出对SIRT2的同工型选择性。基于NMR的构象分析表明，单个类似物的构象偏爱可能有助于它们的同工型选择性。

  DOI：

  10.1021/jm1013852

文献信息

• Two-Step Synthesis of Novel, Bioactive Derivatives of the Ubiquitous Cofactor Nicotinamide Adenine Dinucleotide (NAD)
  作者：Thomas Pesnot、Julia Kempter、Jörg Schemies、Giulia Pergolizzi、Urszula Uciechowska、Tobias Rumpf、Wolfgang Sippl、Manfred Jung、Gerd K. Wagner

  DOI：10.1021/jm1013852

  日期：2011.5.26

  We report the design and concise synthesis, in two steps from commercially available material, of novel, bioactive derivatives of the enzyme cofactor nicotinamide adenine dinucleotide (NAD). The new synthetic dinucleotides act as sirtuin (SIRT) inhibitors and show isoform selectivity for SIRT2 over SIRT1. An NMR-based conformational analysis suggests that the conformational preferences of individual

  我们报告了设计和简洁的合成，从市售材料中分两步合成了酶辅因子烟酰胺腺嘌呤二核苷酸（NAD）的新型生物活性衍生物。新的合成二核苷酸充当sirtuin（SIRT）抑制剂，并且相对于SIRT1表现出对SIRT2的同工型选择性。基于NMR的构象分析表明，单个类似物的构象偏爱可能有助于它们的同工型选择性。
• 2′-Deoxy Cyclic Adenosine 5′-Diphosphate Ribose Derivatives: Importance of the 2′-Hydroxyl Motif for the Antagonistic Activity of 8-Substituted cADPR Derivatives
  作者：Bo Zhang、Gerd K. Wagner、Karin Weber、Clive Garnham、Anthony J. Morgan、Antony Galione、Andreas H. Guse、Barry V. L. Potter

  DOI：10.1021/jm7010386

  日期：2008.3.1

  The structural features needed for antagonism at the cyclic ADP-ribose (cADPR) receptor are unclear. Chemoenzymatic syntheses of novel 8-substituted 2'-deoxy-cADPR analogues, including 8-bromo-2'-deoxy-cADPR 7, 8-amino-2'-deoxy-cADPR 8, 8-O-methyl-2'-deoxy-cADPR 9, 8-phenyl-2'-deoxy-cADPR 10 and its ribose counterpart 8-phenyl-cADPR 5 are reported, including improved syntheses of established antagonists 8-amino-cADPR 2 and 8-bromo-cADPR 3. Aplysia californica ADP-ribosyl cyclase tolerates even the bulky 8-phenyl-nicotinamide adenine 5'-dinucleotide as a substrate. Structure-activity relationships of 8-substituted cADPR analogues in both Jurkat T-lymphocytes and sea urchin egg homogenate (SUH) were investigated. 2'-OH Deletion decreased antagonistic activity (at least for the 8-amino series), showing it to be an important motif. Some 8-substituted 2'-deoxy analogues showed agonist activity at higher concentrations, among which 8-bromo-2'-deoxy-cADPR 7 was, unexpectedly, a weak but almost full agonist in SUH and was membrane-permeant in whole eggs. Classical antagonists 2 and 3 also showed. previously unobserved agonist activity at higher concentrations in both systems. The 2'-OH group, without effect on the Ca(2+)-mobilizing ability of cADPR itself, is an important motif for the antagonistic activities of 8-substituted cADPR analogues.