5-Bromo-UDP | 92706-97-3

• 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: 5-Bromo-UDP
• 英文别名: 5-bromouridine diphosphate；5-bromouridine-5'-diphosphate；((2R,3S,4R,5R)-5-(5-bromo-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl trihydrogen diphosphate；[(2R,3S,4R,5R)-5-(5-bromo-2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphono hydrogen phosphate
• CAS: 92706-97-3
• 化学式: C₉H₁₃BrN₂O₁₂P₂
• 分子量: 483.06
• InChiKey: LEODOYNQKMXKRC-UAKXSSHOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.1
• 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：

  5-Bromo-UDP 在 钯 sodium hydroxide 、 超重氢 作用下， 以 水 为溶剂， 反应 0.5h， 生成
  参考文献：
  名称：

  氚标记的核苷 5'-三磷酸和核苷 5'-二磷酸的合成

  摘要：

  氚标记的核苷 5'-三磷酸 (NTPs) 核苷 5'-二磷酸 (NDP) 在位置 8（在嘌呤核中）和 5（在嘧啶核中）含有氚标记，已通过相应溴的脱卤获得气态氚的衍生物。Br-NTPs 和 Br-NDPs 的脱卤是在大气压力下在碱性水性介质中使用钯催化剂（5% Pd/BaSO4 或 α-Pd）进行的。已经研究了在 5% Pd/BaSO4 存在下通过与气态氚的异质同位素交换反应将氚标记引入腺嘌呤系列核苷酸的可能性。对于合成的化合物，给出了用于色谱分离所需产物的洗脱液的组成。

  DOI：

  10.1007/bf00580035
• 作为产物：
  描述：

  5-溴尿苷 在 磷酸三甲酯 、 1,8-双二甲氨基萘 、 三氯氧磷 、 tris(tributylammonium) phosphate 、 triethylammonium hydrogen bicarbonate buffer 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 5-Bromo-UDP
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Uracil Nucleotide Derivatives and Analogues as Agonists at Human P2Y₂, P2Y₄, and P2Y₆ Receptors

  摘要：

  A series of UTP, UDP, and UMP derivatives and analogues were synthesized and evaluated at the human pyrimidinergic P2Y receptor subtypes P2Y(2), P2Y(4), and P2Y(6) stably expressed in 1321N1 astrocytoma cells. Substituents at N3 of UTP were poorly tolerated by P2Y2 and P2Y4 receptors. In contrast, a large phenacyl substituent at N3 of UDP was well tolerated by the P2Y6 receptor, yielding a potent and selective P2Y6 receptor agonist (3-phenacyl-UDP, EC50 = 70 nM, > 500-fold selective). The most potent and selective P2Y2 receptor agonist of the present series was 2-thio-UTP (EC50 = 50 nM, >= 30-fold selective vs P2Y(4) and P2Y6). All modifications at the uracil base of UTP led to a decrease in potency at the P2Y4 receptor. A beta,gamma-dichloromethylene modification in the triphosphate chain of 5-bromo-UTP was tolerated by all three receptor subtypes, thus opening up a new strategy to obtain ectonucleotide diphosphohydrolase- and phosphatase-resistant P2Y(2), P2Y(4), and P2Y(6) receptor agonists.

  DOI：

  10.1021/jm060848j

文献信息

• Evidence that the p2y3 Receptor Is the Avian Homologue of the Mammalian P2Y₆Receptor
  作者：Qing Li、Melanie Olesky、R. Kyle Palmer、T. Kendall Harden、Robert A. Nicholas

  DOI：10.1124/mol.54.3.541

  日期：1998.9.1

  A P2Y receptor with 65% identity to mammalian P2Y6receptors, termed the p2y3 receptor, was recently cloned from a chick brain cDNA library and was proposed to represent a novel P2Y receptor subtype [ Mol Pharmacol 50: 258–265 (1996)]. We cloned the turkey homologue of the chick p2y3 receptor, which shares high sequence identity (97.6%) with the chick receptor, and we stably expressed this receptor and the rat P2Y6 receptor in 1321N1 human astrocytoma cells. The capacities of uridine and adenine nucleotides to promote inositol phosphate accumulation and intracellular Ca2+ mobilization were determined for both receptors. UDP and 5-bromo-UDP were the most potent agonists and UTP was a less potent full agonist at both receptors. In contrast, adenine nucleotides and nucleotide derivatives were relatively more potent at the turkey p2y3 receptor than at the rat P2Y6 receptor. To determine whether the avian p2y3 receptor defined a new subtype of mammalian P2Y receptor or was a species homologue of the mammalian P2Y6 receptor, we screened two different human genomic libraries and a Southern blot with a p2y3 receptor probe, under low-stringency conditions that allowed the clear identification of the human P2Y6 receptor gene. Our data indicated that the human genome does not contain a receptor that is more homologous to the avian p2y3 receptor than the P2Y6 receptor. Taken together, these data further define the pharmacological selectivities of these UDP-selective receptors and strongly suggest that the avian p2y3 receptor is a species homologue of the mammalian P2Y6receptor.

  最近从雏鸡大脑 cDNA 文库中克隆出了一种与哺乳动物 P2Y6 受体有 65% 相同性的 P2Y 受体，称为 p2y3 受体，并被认为代表了一种新型 P2Y 受体亚型[Mol Pharmacol 50: 258-265 (1996)]。我们克隆了小鸡 p2y3 受体的火鸡同源物，它与小鸡受体具有很高的序列同一性（97.6%），我们在 1321N1 人类星形细胞瘤细胞中稳定表达了这种受体和大鼠 P2Y6 受体。我们测定了尿苷和腺嘌呤核苷酸促进两种受体的磷酸肌醇积累和细胞内 Ca2+ 调动的能力。UDP 和 5-bromo-UDP 是两种受体的最强激动剂，而UTP 是两种受体的较弱的完全激动剂。相反，腺嘌呤核苷酸和核苷酸衍生物对火鸡 p2y3 受体的作用比对大鼠 P2Y6 受体的作用相对更强。为了确定禽类 p2y3 受体是哺乳动物 P2Y 受体的一个新亚型，还是哺乳动物 P2Y6 受体的同源物种，我们在低强度条件下筛选了两个不同的人类基因组文库和一个带有 p2y3 受体探针的 Southern 印迹，从而明确了人类 P2Y6 受体基因。我们的数据表明，人类基因组不包含与禽类 p2y3 受体同源性高于 P2Y6 受体的受体。综上所述，这些数据进一步确定了这些 UDP 选择性受体的药理学选择性，并有力地表明禽类 p2y3 受体是哺乳动物 P2Y6 受体的同源物种。
• Method of treating gastrointestinal tract disease with purinergic receptor agonists
  申请人：——

  公开号：US20020052336A1

  公开（公告）日：2002-05-02

  The invention provides a method of regulating water and mucin secretions and fluid transport in the gastrointestinal tract. The invention also provides a method for treating a gastrointestinal disease in which the mucosal barrier of the gastrointestinal system is impaired. The invention additionally provides a method for correcting disorders of fluid secretion or absorption in the gastrointestinal system. The method comprises administering to a patient a pharmaceutical composition comprising a purinergic P2Y receptor agonist, in an amount effective to regulate water and mucin secretions or to correct abnormal fluid transport in the gastrointestinal tract. The pharmaceutical composition used in this invention comprises a P2Y purinergic receptor agonist such as uridine 5′-diphosphate (UDP), uridine 5′-triphosphate (UTP), cytidine 5′-diphosphate (CDP), cytidine 5′-triphosphate (CTP), adenosine 5′-diphosphate (ADP), adenosine 5′-triphosphate (ATP), and their analogs; and dinucleotide polyphosphate compounds of general Formula (IV). Said compound is prepared in an oral form, an injectable form, or a suppository form, and administered to a patient.

  本发明提供了一种调节胃肠道水和粘蛋白分泌及液体运输的方法。本发明还提供了一种治疗胃肠道系统粘膜屏障受损的胃肠道疾病的方法。本发明还提供了一种纠正胃肠道系统液体分泌或吸收障碍的方法。该方法包括向患者施用一种药物组合物，该药物组合物包含一种嘌呤能 P2Y 受体激动剂，其有效量可调节水和粘蛋白分泌或纠正胃肠道中异常的液体转运。本发明中使用的药物组合物包括 P2Y 嘌呤能受体激动剂，如尿苷 5′-二磷酸（UTP）、尿苷 5′-三磷酸（UTP）、尿苷 5′-二磷酸（UTP）、尿苷 5′-三磷酸（UTP）、胞苷 5′-二磷酸（CDP）、胞苷 5′-三磷酸（CTP）、腺苷 5′-二磷酸（ADP）、腺苷 5′-三磷酸（ATP）及其类似物；以及通式（IV）的二核苷酸多磷酸酯化合物。所述化合物以口服形式、注射形式或栓剂形式制备，并给病人服用。
• Method for treating or preventing inflammatory diseases
  申请人：——

  公开号：US20030125299A1

  公开（公告）日：2003-07-03

  The present invention provides a method of preventing or treating an inflammatory disease, including but not limited to, sinusitis, rhinitis, conjunctivitis, asthma, dermatitis, inflammatory bowel disease, inflammatory collagen vascular diseases, glomerulonephritis, inflammatory skin diseases, and sarcoidosis. The method comprises administrating to a subject a pharmaceutical formulation comprising a nucleotide receptor agonist, such as nucleoside diphosphate, nucleoside triphosphate, or dinucleoside polyphosphate, according to general formula Ia, Ib, IIa, IIb, or III. Preferred indications of the present invention are perennial allergic rhinitis, seasonal allergic rhinitis, infectious allergic rhinitis, and allergic conjunctivitis.

  本发明提供了一种预防或治疗炎症性疾病的方法，包括但不限于鼻窦炎、鼻炎、结膜炎、哮喘、皮炎、炎症性肠病、炎症性胶原血管病、肾小球肾炎、炎症性皮肤病和肉瘤病。该方法包括向受试者施用包含核苷酸受体激动剂的药物制剂，例如二磷酸核苷、三磷酸核苷或多磷酸二核苷，根据通式 Ia、Ib、IIa、IIb 或 III。本发明的优选适应症是常年性过敏性鼻炎、季节性过敏性鼻炎、感染性过敏性鼻炎和过敏性结膜炎。
• Method for treating retinal degeneration with purinergic receptor agonists
  申请人：Peterson M. Ward

  公开号：US20050009778A1

  公开（公告）日：2005-01-13

  The present invention provides a method of preventing or treating retinal degeneration arising from pathophysiological or physical conditions. The method comprises administering to a patient a pharmaceutical composition comprising a purinergic P2Y receptor ligand, in an amount effective to elevate its extracellular concentration to activate retinal glial and neuronal cell surface P2Y receptors and mount a neuroprotective response. Methods of administering including intravitreal bolus and sustained administrations, transscleral delivery, topical, and systemic administrations. The pharmaceutical composition useful in this invention comprises a P2Y purinergic receptor agonist, which include uridine 5′-di- and triphosphate (UDP, UTP) and their analogs, adenosine 5′-diphosphate (ADP) and its analogs, cytidine 5′-di- and triphosphate (CDP, CTP) and their analogs, and dinucleoside polyphosphate compounds.

  本发明提供了一种预防或治疗由病理生理或物理条件引起的视网膜变性的方法。该方法包括向患者施用药物组合物，该药物组合物包含嘌呤能 P2Y 受体配体，其有效量可提高细胞外浓度，从而激活视网膜胶质细胞和神经细胞表面的 P2Y 受体并启动神经保护反应。给药方法包括玻璃体内注射和持续给药、经巩膜给药、局部给药和全身给药。用于本发明的药物组合物包括 P2Y 嘌呤能受体激动剂，其中包括尿苷 5′-二磷酸和三磷酸（UDP、UTP）及其类似物、腺苷 5′-二磷酸（ADP）及其类似物、胞苷 5′-二磷酸和三磷酸（CDP、CTP）及其类似物以及二核苷多磷酸化合物。
• USE OF URIDINE 5'-DIPHOSPHATE AND ANALOGS THEREOF FOR THE TREATMENT OF LUNG DISEASES
  申请人：The University of North Carolina at Chapel Hill

  公开号：EP1011688A1

  公开（公告）日：2000-06-28