2-(propylthio)adenosine-5'-monophosphate | 145782-71-4

• 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
• 英文名称: 2-(propylthio)adenosine-5'-monophosphate
• 英文别名: [(2R,3S,4R,5R)-5-(6-amino-2-propylsulfanylpurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate
• CAS: 145782-71-4
• 化学式: C₁₃H₂₀N₅O₇PS
• 分子量: 421.371
• InChiKey: GAORIKFOSRGMEL-WOUKDFQISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  211
• 氢给体数：
  5
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  2-(propylthio)adenosine-5'-monophosphate 、 氯屈膦酸三正丁胺盐 在 吡啶 、 甲醇 、 三正丁胺 、 N,N'-羰基二咪唑 作用下， 生成 2-(propylthio)-5'-adenylic acid monoanhydride with dichloromethylenebis(phosphonic acid)
  参考文献：
  名称：

  Antagonists of the Platelet P_2T Receptor:  A Novel Approach to Antithrombotic Therapy

  摘要：

  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.

  DOI：

  10.1021/jm981072s
• 作为产物：
  描述：

  2-(丙硫基)腺苷 在 磷酸三乙酯 、 碳酸氢钠 、 三氯氧磷 作用下， 生成 2-(propylthio)adenosine-5'-monophosphate
  参考文献：
  名称：

  Antagonists of the Platelet P_2T Receptor:  A Novel Approach to Antithrombotic Therapy

  摘要：

  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.

  DOI：

  10.1021/jm981072s

文献信息

• Nucleoside-5′-monophosphates as Prodrugs of Adenosine A_2A Receptor Agonists Activated by ecto-5′-Nucleotidase†Contribution to celebrate the 100th anniversary of the Division of Medicinal Chemistry of the American Chemical Society.
  作者：Ali El-Tayeb、Jamshed Iqbal、Andrea Behrenswerth、Michael Romio、Marion Schneider、Herbert Zimmermann、Jürgen Schrader、Christa E. Müller

  DOI：10.1021/jm900538v

  日期：2009.12.10

  Prodrugs of adenosine A2A receptor agonists were developed that are activated by ecto-5′-nucleotidase (ecto-5′-NT, CD73). Because ecto-5′-NT is upregulated in inflamed tissue, the A2A agonists are expected to be released from their prodrug form at the sites of inflammation. 2-(Ar)alkyl-substituted AMP derivatives were synthesized and investigated. Certain 2-substituted AMP derivatives, including 2-hexylthio-AMP

  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
• Phosphorylated A2A Receptor Agonists
  申请人：Schrader Jurgen

  公开号：US20100048501A1

  公开（公告）日：2010-02-25

  A phosphorylated A 2A receptor agonist providing agonist properties on the A 2A receptor after dephosphorylation the phosphorylated A 2A receptor agonist comprises a ribosyl moiety and a purine moiety and being phosphorylated at the 5 ′-position of the ribose moiety except adenosine monophosphate (AMP), adenosine diphosphate (ADP) or adenosine triphosphate (ATP), a medicament containing the compound of the invention including ADP and the use of the compound of the invention including ATP and ADP for several medical indications e. g. inflammatory events. In particular, compounds of formula (I) are also disclosed.

  一种磷酸化的A2A受体激动剂，在去磷酸化后提供A2A受体的激动作用，该磷酸化的A2A受体激动剂包括一个核糖基团和一个嘌呤基团，并在核糖基团的5'-位置被磷酸化，但不包括腺苷酸单磷酸（AMP）、腺苷酸二磷酸（ADP）或腺苷酸三磷酸（ATP）。含有该发明物化合物的药物包括ADP，该发明物化合物的用途包括ATP和ADP用于多种医学适应症，例如炎症事件。特别地，还披露了式（I）的化合物。
• MEDICINAL COMPOSITION FOR TREATING ARTERIOSCLEROSIS
  申请人：Sankyo Company, Limited

  公开号：EP1555032A1

  公开（公告）日：2005-07-20

  [Constitution] A medicinal composition characterized in that an ADP receptor antagonist and an ACAT inhibitor are administered either simultaneously or separately at a defined interval. [Advantage] A medicinal composition, wherein an ADP receptor antagonist and an ACAT inhibitor are administered either simultaneously or separately at a defined interval, is useful as a preventive or a remedy (in particular, a remedy) for arteriosclerosis or diseases derived from arteriosclerosis such as ischemic heart disease, ischemic brain disease and peripheral circulation failure in warm-blooded animals (in particular, humans).

  [章程]一种药物组合物，其特征在于，ADP 受体拮抗剂和 ACAT 抑制剂以规定的间隔同时或分别给药。 [优点]一种药物组合物，其中 ADP 受体拮抗剂和 ACAT 抑制剂以规定的间隔同时或分别给药，可用于预防或治疗（特别是）动脉硬化或动脉硬化引起的疾病，如温血动物（特别是人类）的缺血性心脏病、缺血性脑病和外周循环衰竭。
• Medicinal composition for treating arteriosclerosis
  申请人：Asai Fumitoshi

  公开号：US20050192245A1

  公开（公告）日：2005-09-01

  A medicinal composition, wherein an ADP receptor antagonist and an ACAT inhibitor are administered either simultaneously or separately at a defined interval as a preventive or a remedy (in particular, a remedy) for arteriosclerosis or diseases derived from arteriosclerosis such as ischemic heart disease, ischemic brain disease and peripheral circulation failure in warm-blooded animals (in particular, humans).

  一种药物组合物，其中 ADP 受体拮抗剂和 ACAT 抑制剂可同时或分别以规定的间隔给药，作为温血动物（尤其是人类）动脉硬化或动脉硬化衍生疾病（如缺血性心脏病、缺血性脑病和外周循环衰竭）的预防或治疗（尤其是治疗）药物。
• PHOSPHORYLATED A2A RECEPTOR AGONISTS
  申请人：Schrader, Jürgen

  公开号：EP2021350A1

  公开（公告）日：2009-02-11