(2R,3R,4S,5S)-1-(3,4-dihydroxy-5-(diphosphoryloxymethyl)tetrahydrofuran-2-yl)-5-iodopyrimidine-2,4(1H,3H)-dione | 93906-48-0

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 英文名称: (2R,3R,4S,5S)-1-(3,4-dihydroxy-5-(diphosphoryloxymethyl)tetrahydrofuran-2-yl)-5-iodopyrimidine-2,4(1H,3H)-dione
• 英文别名: 5-iodouridine 5'-diphosphate；5-iodouridine-5′-diphosphate；5-Iodo-UDP；MRS2693；((2R,3S,4R,5R)-3,4-dihydroxy-5-(5-iodo-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methyl trihydrogen diphosphate；[(2R,3S,4R,5R)-3,4-dihydroxy-5-(5-iodo-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl phosphono hydrogen phosphate
• CAS: 93906-48-0
• 化学式: C₉H₁₃IN₂O₁₂P₂
• 分子量: 530.06
• InChiKey: TTYCBCDSPQHLDE-UAKXSSHOSA-N

物化性质

• 密度：
  2.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -4.4
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  212
• 氢给体数：
  6
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  (2R,3R,4S,5S)-1-(3,4-dihydroxy-5-(diphosphoryloxymethyl)tetrahydrofuran-2-yl)-5-iodopyrimidine-2,4(1H,3H)-dione 、 5-醛基-2-噻吩硼酸 在 sodium tetrachloropalladate(II) 、 trisodium tris(3-sulfophenyl)phosphine 、 caesium carbonate 作用下， 以 水 为溶剂， 反应 1.0h， 以77%的产率得到5-(5-formylthien-2-yl)uridine-5′-diphosphate
  参考文献：
  名称：

  探索 5-取代基对 5-芳基和 5-杂芳基尿嘧啶核苷酸的固有荧光的作用：一项系统研究†‡

  摘要：

  UMP 的衍生物 (尿苷一磷酸) 在 5 位有一个荧光取代基，代表了一个小而独特的荧光团，在化学生物学和生物分子化学中发现了重要的应用。在这项研究中，我们合成了一系列在5位具有不同芳香族和杂芳香族取代基的尿嘧啶核苷酸UMP、UDP和UTP的衍生物，以系统地研究5-取代基对荧光发射的影响。我们已经确定了该系列中所有衍生物的相关光物理参数，包括最佳荧光团的量子产率。在尿嘧啶碱基的第 5 位使用 5-formylthien-2-yl 取代基观察到最强的荧光发射，而相应的 3-formylthien-2-yl-取代的区域异构体的荧光显着降低。在不同极性和质子的溶剂中进一步研究了 5-(5-formylthien-2-yl) 尿嘧啶荧光团。结合基于 NMR 数据和计算实验的构象分析结果，这些发现提供了对控制此类荧光团中荧光发射的空间和电子因素的见解。特别是，它们突出了本系列中荧光发射和构象之间的相互作用。最后，我们用

  DOI：

  10.1039/c3ob40485d
• 作为产物：
  描述：

  尿苷5-单磷酸 在 potassium dihydrogenphosphate 、 碘 、 硝酸 作用下， 以 氯仿 、 二甲基亚砜 为溶剂， 反应 18.08h， 生成 (2R,3R,4S,5S)-1-(3,4-dihydroxy-5-(diphosphoryloxymethyl)tetrahydrofuran-2-yl)-5-iodopyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  [EN] DERIVATIVES OF URIDINE PHOSPHATE AND THEIR USES IN PROTEIN BINDING ASSAYS
  [FR] COMPOSÉS ET LEURS UTILISATIONS DANS DES DOSAGES DE LIAISON AUX PROTÉINES

  摘要：

  公开号：

  WO2011051733A3

文献信息

• Structure−Activity Relationships of Uridine 5‘-Diphosphate Analogues at the Human P2Y₆ Receptor
  作者：Pedro Besada、Dae Hong Shin、Stefano Costanzi、Hyojin Ko、Christophe Mathé、Julien Gagneron、Gilles Gosselin、Savitri Maddileti、T. Kendall Harden、Kenneth A. Jacobson

  DOI：10.1021/jm060485n

  日期：2006.9.1

  been studied. Uridine 5'-diphosphate (UDP) analogues bearing substitutions of the ribose moiety, the uracil ring, and the diphosphate group were synthesized and assayed for activity at the human P2Y6 receptor. The uracil ring was modified at the 4 position, with the synthesis of 4-substituted-thiouridine 5'-diphosphate analogues, as well as at positions 2, 3, and 5. The effect of modifications at the

  研究了尿嘧啶核苷酸激活的 P2Y6 受体的结构-活性关系和分子模型。合成了带有核糖部分、尿嘧啶环和二磷酸基团取代的尿苷 5'-二磷酸 (UDP) 类似物，并测定了其对人 P2Y6 受体的活性。尿嘧啶环在 4 位上进行修饰，合成 4-取代的硫尿苷 5'-二磷酸类似物，以及在 2、3 和 5 位进行修饰。研究了磷酸链水平修饰的影响通过制备环状3',5'-二磷酸类似物、3'-二磷酸类似物和几种二核苷酸二磷酸。 5-Iodo-UDP 32 (EC50 = 0.15 microM) 与 UDP 等价，而 2'-羟基（氨基、叠氮基）的取代会大大降低效力。与 UDP 相比，2- 和 4- 硫代类似物分别为 20 和 21 也相对有效。然而，大多数其他修改大大降低了效力。分子模型表明，5'-UDP 和类似物的 β-磷酸对于与受体的三个保守阳离子残基中的两个建立静电相互作用至关重要。在4-硫醚衍生物中，4-乙硫基类似物23显示出0
• DERIVATIVES OF URIDINE PHOSPHATE AND THEIR USES IN PROTEIN BINDING ASSAYS
  申请人：Wagner Gerd

  公开号：US20120219963A1

  公开（公告）日：2012-08-30

  The present invention relates to compounds and their use in competitive protein binding assays, for example for use with glycosyl transferase and/or glycoprocessing proteins. The present application also provides kits and apparatuses for use in the assays. In particular, the present invention provides a compound of the formula (I): wherein n is 1, 2 or 3; R 1 is selected from —OH, —OPO 3 H, —OR 4 , —NHR 4 , R 6 ; R 2 and R 3 are each independently selected from —H, —OH, optionally substituted —O-alkyl and —O-alkanoyl; R 4 is selected from an optionally substituted mono or polysaccharide, -alkyl, -alkenyl, -alkynyl, and L-Z, where L is a linking agent and Z is a binding agent; R 6 is an optionally substituted hydrocarbon group; A is either (i) a substituted heteroaryl group, the substituent on the heteroaryl group having a double bond conjugated to the heteroaryl group, or (ii) a substituted aryl group, the substituent on the aryl group having a double bond conjugated to the aryl group.

  本发明涉及化合物及其在竞争性蛋白结合测定中的应用，例如用于糖基转移酶和/或糖基加工蛋白的应用。本申请还提供用于该测定的试剂盒和装置。具体而言，本发明提供式（I）的化合物：其中n为1、2或3；R1选择自—OH、—OPO3H、—OR4、—NHR4、R6；R2和R3各自独立地选择自—H、—OH、可选地取代的—O-烷基和—O-酰基烷基；R4选择自可选地取代的单糖或多糖、-烷基、-烯基、-炔基和L-Z，其中L是连接剂，Z是结合剂；R6是可选地取代的烃基；A是（i）取代的杂环芳基，杂环芳基上的取代基具有共轭到杂环芳基的双键，或（ii）取代的芳基，芳基上的取代基具有共轭到芳基的双键。
• Synthesis and potency of novel uracil nucleotides and derivatives as P2Y2 and P2Y6 receptor agonists
  作者：Hyojin Ko、Rhonda L. Carter、Liesbet Cosyn、Riccardo Petrelli、Sonia de Castro、Pedro Besada、Yixing Zhou、Loredana Cappellacci、Palmarisa Franchetti、Mario Grifantini、Serge Van Calenbergh、T. Kendall Harden、Kenneth A. Jacobson

  DOI：10.1016/j.bmc.2008.05.013

  日期：2008.6

  The phosphate, uracil, and ribose moieties of uracil nucleotides were varied structurally for evaluation of agonist activity at the human P2Y(2), P2Y(4), and P2Y(6) receptors. The 2-thio modi. cation, found previously to enhance P2Y2 receptor potency, could be combined with other favorable modi. cations to produce novel molecules that exhibit high potencies and receptor selectivities. Phosphonomethylene bridges introduced for stability in analogues of UDP, UTP, and uracil dinucleotides markedly reduced potency. Truncation of dinucleotide agonists of the P2Y(2) receptor, in the form of Up(4)-sugars, indicated that a terminal uracil ring is not essential for moderate potency at this receptor and that specific SAR patterns are observed at this distal end of the molecule. Key compounds reported in this study include 9, alpha, beta-methylene-UDP, a P2Y(6) receptor agonist; 30, Up(4)-phenyl ester and 34, Up(4)-[1] glucose, selective P2Y(2) receptor agonists; dihalomethylene phosphonate analogues 16 and 41, selective P2Y(2) receptor agonists; 43, the 2-thio analogue of INS37217 (P-1-(uridine-5')-P-4-(2'-deoxycytidine-5') tetraphosphate), a potent and selective P2Y(2) receptor agonist. Published by Elsevier Ltd.
• US9018370B2
  申请人：——

  公开号：US9018370B2

  公开（公告）日：2015-04-28
• [EN] COMPOUNDS AND THEIR USES IN PROTEIN BINDING ASSAYS<br/>[FR] COMPOSÉS ET LEURS UTILISATIONS DANS DES DOSAGES DE LIAISON AUX PROTÉINES
  申请人：UNIV EAST ANGLIA

  公开号：WO2011051733A2

  公开（公告）日：2011-05-05

  The present invention relates to compounds and their use in competitive protein binding assays, for example for use with glycosyl transferase and/or glycoprocessing proteins. The present application also provides kits and apparatuses for use in the assays. In particular, the present invention provides a compound of the formula (I): wherein n is 1, 2 or 3; R1 is selected from -OH, -OPO3H, -OR4, -NHR4, R6; R2 and R3 are each independently selected from -H, -OH, optionally substituted -O- alkyl and -O-alkanoyl; R4 is selected from an optionally substituted mono or polysaccharide, -alkyl, -alkenyl, - alkynyl, and L-Z, where L is a linking agent and Z is a binding agent; R6 is an optionally substituted hydrocarbon group; A is either (i) a substituted heteroaryl group, the substituent on the heteroaryl group having a double bond conjugated to the heteroaryl group, or (ii) a substituted aryl group, the substituent on the aryl group having a double bond conjugated to the aryl group.