uridine 5'-O-(3-thiotriphosphate) | 79049-97-1

• 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: uridine 5'-O-(3-thiotriphosphate)
• 英文别名: uridine-5'-O-(3-thiotriphosphate)；uridine 5'-O-3-thiotriphosphate；UTPγS；UTP-γ-S；1-thio-triphosphoric acid 3-uridin-5'-yl ester；Uridin-5'-O-(3-thiotriphosphat)；UTPgammaS；dihydroxyphosphinothioyl [[(2R,3S,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] hydrogen phosphate
• CAS: 79049-97-1
• 化学式: C₉H₁₅N₂O₁₄P₃S
• 分子量: 500.21
• InChiKey: DUDALCZPYHIGIR-XVFCMESISA-N

物化性质

• 密度：
  2.030±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -4.1
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  274
• 氢给体数：
  7
• 氢受体数：
  15

反应信息

• 作为产物：
  描述：

  鸟苷 5'-(四氢 5-硫代三磷酸酯) 、 尿苷-5’-二磷酸 在 nucleotide diphosphate kinase 作用下， 生成 uridine 5'-O-(3-thiotriphosphate)
  参考文献：
  名称：

  Uridine nucleotide-induced stimulation of gluconeogenesis in isolated rat proximal tubules

  摘要：

  Uridine nucleotides, released into the extracellular environment, influence a variety of metabolic and other cellular activities in a wide range of target tissues. Here we have studied the effects of uridine nucleotides on gluconeogenesis in isolated rat proximal tubules. Gluconeogenesis, from a range of precursors, was stimulated following exposure of isolated proximal tubules to either UTP or UTPgammaS, but not when exposed to other uridine-containing nucleotides. UTP- and UTPgammaS-induced gluconeogenesis was diminished in the presence of purinoceptor antagonists (e.g. suramin, PPADS) indicative of a role for P2Y(2)-like purinoceptors in these effects. Likewise, agents that interfere with either phospholipase C activation or intracellular Ca2+ mobilization decreased UTP- and UTPgammaS-induced stimulation of gluconeogenesis consistent with a role for these secondary messenger systems in the mechanism of action of extracellular UTP and UTPgammaS on proximal tubule metabolism.

  DOI：

  10.1007/s00210-002-0571-9

文献信息

• Enzymatic synthesis of UTPγS, a potent hydrolysis resistant agonist of P2U-purinoceptors
  作者：Eduardo R. Lazarowski、William C. Watt、M. Jackson Stutts、H. Alex Brown、Richard C. Boucher、T. Kendall Harden

  DOI：10.1111/j.1476-5381.1996.tb15175.x

  日期：1996.1

  secretory pathway that is activated by extracellular nucleotides, e.g. uridine-5'triphosphate (UTP), acting on P2U purinoceptors. Since UTP is susceptible to hydrolysis by nucleotidases and phosphatases present in the airways, the identification of stable P2U-purinoceptor agonists would be of therapeutic relevance. 2. Uridine-5'-O-(3-thiotriphosphate) (UTP gamma S) was synthesized by nucleoside diphosphate

  1.囊性纤维化气道上皮细胞的缺陷性C1分泌特性可通过作用于P2U嘌呤受体的胞外核苷酸（如尿苷5'三磷酸（UTP））激活的另一种依赖Ca2 +的Cl分泌途径来绕过。由于UTP易被呼吸道中存在的核苷酸酶和磷酸酶水解，因此鉴定稳定的P2U-嘌呤受体激动剂将具有治疗意义。2.尿苷5'-O-（3-硫代三磷酸）（UTPγS）是通过核苷二磷酸激酶催化的鸟苷5'-O-（3-硫代三磷酸）（GTPγS）转移γ-硫代磷酸酯而合成的。 ）或腺苷5'= O-（3-硫代三磷酸）（ATPγS）到UDP。通过观察从[35S] -GTPγS转移35S和从[3H] -UDP转移3H来说明UTPγS的形成。通过核磁共振分析证实了高效液相色谱（hplc）纯化的UTPγS的化学特性。3.利用稳定表达磷脂酶C偶联的人P2U-嘌呤受体的人1321N1星形细胞瘤细胞测试UTPγS的活性。UTPγS（EC50 = 240 nM）与UTP和ATP基本等价，以刺激肌醇磷酸形成。
• METHOD OF PROMOTING CERVICAL AND VAGINAL SECRETIONS
  申请人：——

  公开号：US20020013289A1

  公开（公告）日：2002-01-31

  The present invention provides a method of stimulating cervical and vaginal secretions in a mammal by treatment with P2Y 2 and/or P2Y 4 purinergic receptor agonists. Treatment of vaginal dryness associated with menopause, chemotherapy, and various disease states as well as the treatment of vulvar pain is discussed. Suitable agonists such as UTP, CTP, ATP, dinucleotides and analogs thereof are disclosed.

  本发明提供了一种通过使用P2Y2和/或P2Y4嘌呤受体激动剂来刺激哺乳动物的子宫颈和阴道分泌物的方法。讨论了与更年期、化疗和各种疾病状态相关的阴道干燥的治疗以及外阴疼痛的治疗。公开了适合的激动剂，如UTP、CTP、ATP、二核苷酸及其类似物。
• Conjugates of sodium channel blockers and methods of using the same
  申请人：——

  公开号：US20020165239A1

  公开（公告）日：2002-11-07

  Compounds of the general formula P 1 -L-P 2 ; wherein “P 1 ” is a pyrazinoylguanidine sodium channel blocker, “L” is a linking group, and “P 2 ” is either (i) a pyrazinoylguanidine sodium channel blocker or (ii) a P2Y 2 receptor agonist, are disclosed. Pharmaceutical formulations containing the same and methods of use thereof to hydrate mucosal surfaces such as airway mucosal surfaces are also disclosed.

  本发明揭示了一般式为P1-L-P2的化合物；其中“P1”是吡嗪酰基胍钠通道阻滞剂，“L”是连接基团，“P2”是（i）吡嗪酰基胍钠通道阻滞剂或（ii）P2Y2受体激动剂。还揭示了含有上述化合物的制药配方以及将其用于使黏膜表面如呼吸道黏膜表面保湿的方法。
• Method for identifying purinergic modulators of the olfactory system
  申请人：The University Of Utah

  公开号：EP2410332A1

  公开（公告）日：2012-01-25

  Disclosed are screening methods for detecting compounds that modulate odor sensitivity via purinergic receptors of the olfactory system.

  所公开的是用于检测通过嗅觉系统的嘌呤能受体调节气味敏感性的化合物的筛选方法。
• COMPOUNDS AND METHODS FOR INHIBITING PHOSPHATE TRANSPORT
  申请人：Ardelyx, Inc.

  公开号：EP3492106A1

  公开（公告）日：2019-06-05

  Provided are non-NHE3-binding agents having activity as phosphate transport/uptake inhibitors in the gastrointestinal tract, including in the small intestine, methods for their use as therapeutic or prophylactic agents, and related methods of drug discovery.

  本文提供了在胃肠道（包括小肠）中作为磷酸盐转运/摄取抑制剂而具有活性的非 NHE3 结合剂、将其用作治疗或预防药物的方法以及相关的药物发现方法。