2-(丙硫基)腺苷 | 31528-53-7

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 中文名称: 2-(丙硫基)腺苷
• 英文名称: 2-propylthioadenosine
• 英文别名: 2-(n-Propylthio)adenosine；(2R,3R,4S,5R)-2-(6-amino-2-propylsulfanylpurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 31528-53-7
• 化学式: C₁₃H₁₉N₅O₄S
• 分子量: 341.391
• InChiKey: RZECJIGAYNYQAD-WOUKDFQISA-N

物化性质

• 沸点：
  727.2±70.0 °C(Predicted)
• 密度：
  1.79±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  165
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2-(丙硫基)腺苷 在 磷酸三甲酯 、 1,8-双二甲氨基萘 、 三氯氧磷 作用下， 反应 5.0h， 生成
  参考文献：
  名称：

  核苷5'-单磷酸盐作为被ecto-5'-核苷酸酶激活的腺苷A 2A受体激动剂的前药† † 为庆祝美国化学学会药物化学100周年而做的贡献。

  摘要：

  开发了腺苷A 2A受体激动剂的前药，它们被ecto-5'-核苷酸酶（ecto-5'-NT，CD73）激活。由于ecto-5'-NT在发炎的组织中上调，因此A 2A激动剂有望在炎症部位从其前药形式释放出来。合成并研究了2-（Ar）烷基取代的AMP衍生物。某些2-取代的AMP衍生物，包括2-己基硫基-AMP，2-环戊基硫基-AMP，2-环己基甲硫基-AMP和2-环己基乙硫基-AMP被ecto-5'-NT接受为底物，并易于转化为相应的2取代的腺苷衍生物。2-环己基乙硫基取代是ecto-5'-NT和腺苷A 2A的良好折衷方案受体。相应的AMP衍生物（12g）是与AMP本身相似的良好底物，而所得的腺苷衍生物（11g）是相对有效的A 2A激动剂（放射配体与大鼠脑纹状体膜的结合力：K i = 372 nM；抑制抗-在小鼠CD4 +细胞中CD3 /抗CD28诱导的IFN-γ释放：EC 50 = 50 nM

  DOI：

  10.1021/jm900538v
• 作为产物：
  描述：

  2-硫代腺苷酸 在 sodium hydroxide 作用下， 以 甲醇 、 水 、 1-碘代丙烷 为溶剂， 生成 2-(丙硫基)腺苷
  参考文献：
  名称：

  ADP and ATP analogues, process for making and administration to inhibit

  摘要：

  公式I的化合物已被披露，其中Q代表CR.sup.1 R.sup.2，R代表O或CR.sup.3 R.sup.4，W代表O或CH.sub.2，R.sup.1，R.sup.2，R.sup.3和R.sup.4分别代表氢或卤素，X代表S(O).sub.n R.sup.5，烷基C.sub.1-6，烷氧基C.sub.1-6，酰胺基C.sub.1-6，CONR.sup.6 R.sup.7，NR.sup.8 R.sup.9，卤素，含有5-或6-成员的含硫杂环，或苯基，可选地由烷基C.sub.1-6取代，n代表0、1或2，R.sup.5代表芳基或烷基C.sub.1-6，可选地由一个或多个亲水基、烷氧基C.sub.1-6、卤素和芳基取代的基团取代；R.sup.6，R.sup.7，R.sup.8和R.sup.9独立地代表氢或烷基C.sub.1-6，Y代表NH.sub.2或烷氧基C.sub.1-6，Z代表酸性基团，此外，当R代表CR.sup.3 R.sup.4时，--Q--Z也可以代表羟基或--OP(O)(OH).sub.2，及其药学上可接受的盐，具有某些限制条件，用作药物。

  公开号：

  US05654285A1

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)。
• New highly active antiplatelet agents with dual specificity for platelet P2Y1 and P2Y12 adenosine diphosphate receptors
  作者：Ivan B. Yanachkov、Hung Chang、Milka I. Yanachkova、Edward J. Dix、Michelle A. Berny-Lang、Thomas Gremmel、Alan D. Michelson、George E. Wright、Andrew L. Frelinger

  DOI：10.1016/j.ejmech.2015.10.055

  日期：2016.1

  Currently approved platelet adenosine diphosphate (ADP) receptor antagonists target only the platelet P2Y(12) receptor. Moreover, especially in patients with acute coronary syndromes, there is a strong need for rapidly acting and reversible antiplatelet agents in order to minimize the risk of thrombotic events and bleeding complications. In this study, a series of new P-1,P-4-di(adenosine-5') tetraphosphate (Ap(4)A) derivatives with modifications in the base and in the tetraphosphate chain were synthesized and evaluated with respect to their effects on platelet aggregation and function of the platelet P2Y(1), P2Y(12), and P2X1 receptors. The resulting structure activity relationships were used to design Ap(4)A analogs which inhibit human platelet aggregation by simultaneously antagonizing both P2Y(1) and P2Y(12) platelet receptors. Unlike Ap(4)A, the analogs do not activate platelet P2X1 receptors. Furthermore, the new compounds exhibit fast onset and offset of action and are significantly more stable than Ap(4)A to degradation in plasma, thus presenting a new promising class of antiplatelet agents. (C) 2015 Elsevier Masson SAS. All rights reserved.
• Antagonists of the Platelet P<i>_2T</i> Receptor:  A Novel Approach to Antithrombotic Therapy
  作者：Anthony H. Ingall、John Dixon、Andrew Bailey、Mandy E. Coombs、David Cox、Judith I. McInally、Simon F. Hunt、Nicholas D. Kindon、Barry J. Teobald、Paul A. Willis、Robert G. Humphries、Paul Leff、Jane A. Clegg、James A. Smith、Wendy Tomlinson

  DOI：10.1021/jm981072s

  日期：1999.1.1

  The platelet P(2T) receptor plays a major role in platelet aggregation, and its antagonists are predicted to have significant therapeutic potential as antithrombotic agents. We have explored analogues of adenosine triphosphate (ATP), which is a weak, nonselective but competitive P(2T) receptor antagonist. Modification of the polyphosphate side chain to prevent breakdown to the agonist adenosine diphosphate (ADP) and substitution of the adenine moiety to enhance affinity and selectivity for the P(2T) receptor led to the identification of 10e (AR-C67085MX), having an IC(50) Of 2.5 nM against ADP-induced aggregation of human platelets. Compound 10e was the first very potent antagonist of the P(2T) receptor, with a selectivity for that subtype of the P2 receptor family of >1000-fold. Further modification of the structure produced compound 101 (AR-C69931MX) having an IC(50) of 0.4 nM. In vivo, at maximally effective antithrombotic doses, there is little prolongation of bleeding time (1.4-fold), which is in marked contrast to the 5-6-fold found with GPIIb/lIIa antagonists.
• Synthesis and preliminary evaluation of [3H]PSB-0413, a selective antagonist radioligand for platelet P2Y12 receptors
  作者：Ali El-Tayeb、Kerstin J. Griessmeier、Christa E. Müller

  DOI：10.1016/j.bmcl.2005.08.104

  日期：2005.12

  The selective antagonist radioligand [H-3]2-propylthioadenosine-5-adenylic acid (1,1-dichloro-l-phosphonomethyl-l-phosphonyl) anhydride ([H-3]PSB-0413) was prepared by catalytic hydrogenation of its propargyl precursor with a high specific radioactivity of 74 Ci/mmol. In preliminary saturation binding studies, [H-3]PSB-0413 showed high affinity for platelet P2Y(12) receptors with a K-D value of 4.57 nM. Human platelets had a high density of P2Y(12) receptors exhibiting a B-max value of 7.66 pmol/mg of protein. (c) 2005 Elsevier Ltd. All rights reserved.
• ATP analogues
  申请人：Astra Pharmaceuticals Limited

  公开号：EP0508687B1

  公开（公告）日：1995-09-13