8-phenyl-adenosine 5'-monophosphate morpholidate | 1018828-91-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 8-phenyl-adenosine 5'-monophosphate morpholidate
• 英文别名: [(2R,3S,4R,5R)-5-(6-amino-8-phenylpurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-morpholin-4-ylphosphinic acid
• CAS: 1018828-91-5
• 化学式: C₂₀H₂₅N₆O₇P
• 分子量: 492.428
• InChiKey: LQKAJEOOJFVHRK-KHTYJDQRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  178
• 氢给体数：
  4
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  8-phenyl-adenosine 5'-monophosphate morpholidate 、 β-烟酰胺单核苷酸 在 magnesium sulfate 、 manganese(ll) chloride 作用下， 以 formamide 为溶剂， 反应 12.0h， 以41%的产率得到C₂₇H₃₁N₇O₁₄P₂
  参考文献：
  名称：

  Base-modified NAD and AMP derivatives and their activity against bacterial DNA ligases

  摘要：

  2-取代NAD⁺衍生物是NAD⁺依赖的细菌DNA连接酶的较差底物，但是是中等抑制剂，与NAD⁺协同作用。

  DOI：

  10.1039/c5ob00294j
• 作为产物：
  描述：

  5'-腺嘌呤核苷酸 在 potassium dihydrogenphosphate 、 sodium tetrachloropalladate(II) 、 trisodium tris(3-sulfophenyl)phosphine 、 溴 、 potassium carbonate 作用下， 以 水 、 二甲基亚砜 为溶剂， 反应 3.08h， 生成 8-phenyl-adenosine 5'-monophosphate morpholidate
  参考文献：
  名称：

  A novel fluorescent probe for NAD-consuming enzymes

  摘要：

  三种不同的消耗 NAD 的酶将一种新型荧光 NAD 衍生物作为底物进行处理。这种新探针已被用于通过荧光变化连续监测酶活性，并在一种情况下直接观察替代反应途径。

  DOI：

  10.1039/c1cc15499k

文献信息

• Structure–Activity Relationship of Adenosine 5′-diphosphoribose at the Transient Receptor Potential Melastatin 2 (TRPM2) Channel: Rational Design of Antagonists
  作者：Christelle Moreau、Tanja Kirchberger、Joanna M. Swarbrick、Stephen J. Bartlett、Ralf Fliegert、Timur Yorgan、Andreas Bauche、Angelika Harneit、Andreas H. Guse、Barry V. L. Potter

  DOI：10.1021/jm401497a

  日期：2013.12.27

  Adenosine S'-diphosphoribose (ADPR) activates TRPM2, a Ca2+, Na+, and K+ permeable cation channel. Activation is induced by ADPR binding to the cytosolic C-terminal NudT9-homology domain. To generate the first structure activity relationship, systematically modified ADPR analogues were designed, synthesized, and evaluated as antagonists using patch-clamp experiments in HEK293 cells overexpressing human TRPM2. Compounds with a purine C8 substituent show antagonist activity, and an 8-phenyl substitution (8-Ph-ADPR, 5) is very effective. Modification of the terminal ribose results in a weak antagonist, whereas its removal abolishes activity. An antagonist based upon a hybrid structure, 8-phenyl-2'-deoxy-ADPR (86, IC50 = 3 mu M), is more potent than 8-Ph-ADPR (5). Initial bioisosteric replacement of the pyrophosphate linkage abolishes activity, but replacement of the pyrophosphate and the terminal ribose by a sulfarnate-based group leads to a weak antagonist, a lead to more drug-like analogues. 8-Ph-ADPR (5) inhibits Ca2+ signalling and chemotaxis in human neutrophils, illustrating the potential for pharmacological intervention at TRPM2.
• 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.
• Base-modified NAD and AMP derivatives and their activity against bacterial DNA ligases
  作者：Giulia Pergolizzi、Marco M. D. Cominetti、Julea N. Butt、Robert A. Field、Richard P. Bowater、Gerd K. Wagner

  DOI：10.1039/c5ob00294j

  日期：——

  2-Substituted NAD⁺ derivatives are poor substrates, but moderate inhibitors for NAD⁺-dependent bacterial DNA ligases, acting synergistically with NAD⁺.

  2-取代NAD⁺衍生物是NAD⁺依赖的细菌DNA连接酶的较差底物，但是是中等抑制剂，与NAD⁺协同作用。
• A novel fluorescent probe for NAD-consuming enzymes
  作者：Giulia Pergolizzi、Julea N. Butt、Richard P. Bowater、Gerd K. Wagner

  DOI：10.1039/c1cc15499k

  日期：——

  A novel, fluorescent NAD derivative is processed as substrate by three different NAD-consuming enzymes. The new probe has been used to monitor enzymatic activity in a continuous format by changes in fluorescence and, in one case, to directly visualize alternative reaction pathways.

  三种不同的消耗 NAD 的酶将一种新型荧光 NAD 衍生物作为底物进行处理。这种新探针已被用于通过荧光变化连续监测酶活性，并在一种情况下直接观察替代反应途径。