5-磷酸-2-甲基硫代腺苷酸 | 22140-20-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 中文名称: 5-磷酸-2-甲基硫代腺苷酸
• 英文名称: 2-methylthioadenosine 5'-monophosphate
• 英文别名: 2-Methylthio-AMP；[(2R,3S,4R,5R)-5-(6-amino-2-methylsulfanylpurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate
• CAS: 22140-20-1
• 化学式: C₁₁H₁₆N₅O₇PS
• 分子量: 393.317
• InChiKey: XVTFTCNRRAQHEQ-KQYNXXCUSA-N

物化性质

• 溶解度：
  H2O：可溶，20mg/mL，透明，无色

计算性质

• 辛醇/水分配系数(LogP)：
  -2.7
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  211
• 氢给体数：
  5
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  2-甲硫基腺苷 在 磷酸三甲酯 、 三氯氧磷 作用下， 生成 5-磷酸-2-甲基硫代腺苷酸
  参考文献：
  名称：

  [EN] NOVEL ANTITHROMBOTIC DIADENOSINE TETRAPHOSPHATES AND RELATED ANALOGS
  [FR] NOUVEAUX DIADÉNOSINE TÉTRAPHOSPHATES ANTITHROMBOTIQUES ET ANALOGUES ASSOCIÉS

  摘要：

  这项发明涉及化合物的公式I和它们作为抗血小板和抗血栓化合物使用的方法：H /N=Qχ2 O O O O Λ Q2 — N, H R6/ N I f ) ( ^ XM O-Mγτ OM°τ X1MQ' ) r ( ^rf HO OH HO OQHi Nχi R2 公式(I)。

  公开号：

  WO2010059215A1

文献信息

• [EN] NOVEL ANTITHROMBOTIC DIADENOSINE TETRAPHOSPHATES AND RELATED ANALOGS<br/>[FR] NOUVEAUX DIADÉNOSINE TÉTRAPHOSPHATES ANTITHROMBOTIQUES ET ANALOGUES ASSOCIÉS
  申请人：GLSYNTHESIS INC

  公开号：WO2010059215A1

  公开（公告）日：2010-05-27

  The invention features compounds of formula I and methods of their use as antiplatelet and antithrombotic compounds: H /N=Qχ2 O O O O Λ Q2 — N, H R6/ N I f ) ( ^ XM O-Mγτ OM°τ X1MQ' ) r ( ^rf HO OH HO OQHi Nχi R2 Formula (I).

  这项发明涉及化合物的公式I和它们作为抗血小板和抗血栓化合物使用的方法：H /N=Qχ2 O O O O Λ Q2 — N, H R6/ N I f ) ( ^ XM O-Mγτ OM°τ X1MQ' ) r ( ^rf HO OH HO OQHi Nχi R2 公式(I)。
• Identification of hydrolytically stable and selective P2Y1 receptor agonists
  作者：Shay E. Eliahu、Jean Camden、Joanna Lecka、Gary A. Weisman、Jean Sévigny、Sylvie Gélinas、Bilha Fischer

  DOI：10.1016/j.ejmech.2008.07.015

  日期：2009.4

  and enzymatic instabilities. To identify drug candidates, we developed non-hydrolyzable P2YR agonists. We synthesized ATP-β,γ-CH2 analogues 2–4, and evaluated their chemical and metabolic stabilities and activities at P2Y1,2,4,6 receptors. Analogues 2–4 exhibited t1/2 values of 14.5–65 h in gastric juice pH. They were completely resistant to alkaline phosphatase for 30 min at 37 °C and slowly hydrolyzed

  P2Y 核苷酸受体 (P2YRs) 是有吸引力的药物靶点。大多数作为药物提出的 P2YR 激动剂由核苷酸支架组成，但由于其化学和酶学不稳定性，它们的使用受到限制。为了鉴定候选药物，我们开发了不可水解的 P2YR 激动剂。我们合成了 ATP-β,γ-CH 2类似物2 – 4，并评估了它们在 P2Y 1,2,4,6受体上的化学和代谢稳定性和活性。类似物2 - 4展出吨1/2的胃液的pH 14.5-65ħ值。它们在 37°C 下对碱性磷酸酶完全耐受 30 分钟，并在人血清中缓慢水解（t 1/212.7–71.9 小时）。与 ATP 相比，类似物2 – 4几乎不被三磷酸核苷二磷酸水解酶 NTPDase1,2,3,8（<8% 水解）和核苷酸焦磷酸酶 NPP1,3（水解≤10%）水解。类似物2和4B是 P2Y 1 R 的选择性激动剂，EC 50 s 分别为 0.08 和 17.2 μM。这些特征使类似物2和4B
• Blood collection devices containing blood stabilization agent including variegin or analog thereof and/or a polysulfated disaccharide
  申请人：Gelfand Craig A.

  公开号：US10299714B2

  公开（公告）日：2019-05-28

  Disclosed are devices for collecting and stabilizing blood that contain a blood stabilization agent which includes variegin or an analog thereof, a polysulfated disaccharide, or a combination thereof, each in an amount effective to stabilize blood. Methods of making and using the devices, and kits containing the devices, are also provided.

  所公开的是用于收集和稳定血液的装置，其中含有血液稳定剂，该稳定剂包括变异素或其类似物、多硫化二糖或其组合，每种稳定剂的用量都能有效稳定血液。此外，还提供了制造和使用这些装置的方法，以及含有这些装置的试剂盒。
• Nucleotide regulation of immune responses
  申请人：Granstein D. Richard

  公开号：US20050053612A1

  公开（公告）日：2005-03-10

  The invention provides purine receptor agonists and antagonists that are useful for modulating an immune response in an animal. Methods for modulating an inmmune response in an animal are also provided.

  本发明提供了可用于调节动物免疫反应的嘌呤受体激动剂和拮抗剂。本发明还提供了调节动物免疫反应的方法。
• Adenine Nucleotide Analogues Locked in a Northern Methanocarba Conformation:  Enhanced Stability and Potency as P2Y₁ Receptor Agonists
  作者：R. Gnana Ravi、Hak Sung Kim、Jörg Servos、Herbert Zimmermann、Kyeong Lee、Savitri Maddileti、José L. Boyer、T. Kendall Harden、Kenneth A. Jacobson

  DOI：10.1021/jm010538v

  日期：2002.5.1

  Preference for the Northern (N) ring conformation of the ribose moiety of nucleotide 5'-triphosphate agonists at P2Y(1), P2Y(2), P2Y(4), and P2Y(11) receptors, but not P2Y(6) receptors, was established using a ring-constrained methanocarba (a 3.1.0-bicyclohexane) ring as a ribose substitute (Kim et al. J. Med. Chem. 2002, 45, 208-218.). We have now combined the ring-constrained (N)-methanocarba modification of adenine nucleotides with other functionalities known to enhance potency at P2 receptors. The potency of the newly synthesized analogues was determined in the stimulation of phospholipase C through activation of turkey erythrocyte P2Y, or human P2Y, and P2Y2 receptors stably expressed in astrocytoma cells. An (N)methanocarba-2-methylthio-ADP analogue displayed an EC50 at the hP2Y(1) receptor of 0.40 nM and was 55-fold more potent than the corresponding triphosphate and 16-fold more potent than the riboside 5'-diphosphate. 2-Cl-(N)-methanocarba-ATP and its N-6-Me analogue were also highly selective, full agonists at P2Y, receptors. The (N)-methanocarba-2-methylthio and 2-chloromonophosphate analogues were full agonists exhibiting micromolar potency at P2Y(1) receptors, while the corresponding ribosides were inactive. Although beta,y-methylene-ATP was inactive at P2Y receptors beta,y-methylene-(N)-methanocarba-ATP was a potent hP2Y1 receptor agonist with an EC50 of 160 nM and was selective versus hP2Y(2) and hP2Y(4) receptors. The rates of hydrolysis of Northern (N) and Southern (S) methanocarba analogues of AMP by rat 5'-ectonucleotidase were negligible. The rates of hydrolysis of the corresponding triphosphates by recombinant rat NTPDase 1 and 2 were studied. Both isomers were hydrolyzed by NTPDase 1 at about half the rate of ATP hydrolysis. The (N) isomer was hardly hydrolyzed by NTPDase 2, while the (S) isomer was hydrolyzed at one-third of the rate of ATP hydrolysis. This suggests that new, more stable and selective nucleotide agonists may be designed on the basis of the (N)-conformation, which greatly enhanced potency at P2Y, receptors.