2-甲硫基腺苷 | 4105-39-9

• 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-甲硫基腺苷
• 英文名称: 2-(methylthio)adenosine
• 英文别名: 2-Methylthioadenosin；2-Methylmercapto-adenosin；2-Methylthioadenosine；(2R,3R,4S,5R)-2-(6-amino-2-methylsulfanylpurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 4105-39-9
• 化学式: C₁₁H₁₅N₅O₄S
• 分子量: 313.337
• InChiKey: AJNDEAZTAFKOOO-KQYNXXCUSA-N

物化性质

• 熔点：
  225 °C
• 沸点：
  747.6±70.0 °C(Predicted)
• 密度：
  1.98±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  165
• 氢给体数：
  4
• 氢受体数：
  9

制备方法与用途

2-甲硫基腺苷是一种嘌呤核苷类似物，而嘌呤核苷类似物具有广泛的抗肿瘤活性，尤其针对惰性淋巴系统恶性肿瘤。其抗癌机制主要通过抑制DNA合成和诱导细胞凋亡来实现。

反应信息

• 作为反应物：
  描述：

  2-甲硫基腺苷 在 sodium acetate 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 13.0h， 生成 2-methylthio-N⁶-methyladenosine
  参考文献：
  名称：

  New highly active antiplatelet agents with dual specificity for platelet P2Y1 and P2Y12 adenosine diphosphate receptors

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2015.10.055
• 作为产物：
  描述：

  2-甲基硫代-1H-嘌呤-6-胺 在 sodium methylate 、 四氯化锡 作用下， 以 甲醇 、 硝基甲烷 为溶剂， 反应 20.0h， 生成 2-甲硫基腺苷
  参考文献：
  名称：

  HIV-1 A 环和 tRNALys,3 的 RNA 复合物通过核苷修饰稳定

  摘要：

  HIV 转录起始复合物涉及引物 tRNA 反密码子和 HIV 基因组中保守的富含 A 环之间的假定相互作用。表面等离子体共振用于证明 tRNA 反密码子茎环 (ASL) 中的超修饰核苷在反密码子/A 环复合物模型中稳定 RNA-RNA 相互作用。带有大肠杆菌 tRNALys 和人类 tRNALys 修饰的 tRNA ASL 发夹，3 各自形成稳定的复合物。部分修饰的 tRNA ASL 以较低的亲和力结合 A 环发夹，并且发现细菌和哺乳动物 tRNA 的修饰对稳定 RNA 复合物做出了不同的贡献。与已知的对 tRNA 结构和功能的修饰效果一致的反密码子/A 环 RNA 复合物模型是互补 tRNA，

  DOI：

  10.1021/ja028015f

文献信息

• [EN] THERAPUETIC USES OF SELECTED PYRIMIDINE COMPOUNDS WITH ANTI-MER TYROSINE KINASE ACTIVITY<br/>[FR] UTILISATIONS THÉRAPEUTIQUES DE COMPOSÉS SÉLECTIONNÉS DE PYRIMIDINE AYANT UNE ACTIVITÉ TYROSINE KINASE ANTIMÈRE
  申请人：UNIV NORTH CAROLINA

  公开号：WO2015157127A1

  公开（公告）日：2015-10-15

  Uses of pyrimidines with anti-Mer tyrosine kinase activity as anti-infective agents, immunostimulatory and immunomodulatory agents, anti-cancer agents (including against MerTK -/- tumors and ITD and TKD mutant forms of Acute Myeloid Leukemia (AML)), and as adjunctive agents in combination with chemotherapeutic, radiation or other standard of care for neoplasms.

  将嘧啶类化合物用作抗Mer酪氨酸激酶活性的抗感染剂、免疫刺激剂和免疫调节剂、抗癌剂（包括对MerTK -/-肿瘤和急性髓样白血病（AML）的ITD和TKD突变形式），以及作为辅助剂与化疗、放疗或其他肿瘤标准治疗联合使用。
• [EN] ARYL AMINOPYRIMIDINES AS DUAL MERTK AND TYRO3 INHIBITORS AND METHODS THEREOF<br/>[FR] ARYLAMINOPYRIMIDINES UTILISÉES EN TANT QU'INHIBITEURS DOUBLES DE MERTK ET DE TYRO3 ET LEURS PROCÉDÉS
  申请人：UNIV NORTH CAROLINA CHAPEL HILL

  公开号：WO2021097326A1

  公开（公告）日：2021-05-20

  Aminopyrimidine containing compounds that inhibit both Mer tyrosine kinase (MerTK) activity and Tyro3 kinase activity are disclosed herein. Additionally disclosed are methods of synthesis and use of the aminopyrimidine containing compounds as anti-cancer agents, immunostimulatory and immunomodulatory agents, anti-platelet agents, anti-infective agents, and as adjunctive agents.

  本文披露了含有氨基嘧啶的化合物，可以抑制Mer酪氨酸激酶（MerTK）活性和Tyro3激酶活性。此外，还披露了使用含有氨基嘧啶的化合物作为抗癌药物、免疫刺激剂和免疫调节剂、抗血小板药物、抗感染剂以及辅助剂的合成和使用方法。
• [EN] SUBSTITUTED 2-PHENYL-PYRIDINE DERIVATIVES<br/>[FR] DÉRIVÉS DE 2-PHÉNYL-PYRIDINE SUBSTITUÉS
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2009125366A1

  公开（公告）日：2009-10-15

  The present invention relates to compounds of formula (I) wherein R1, R2, R4, R5, Ra, Rb, n, W and Z are as defined in the application, their preparation and their use as P2Y12 receptor antagonists in the treatment and/or prevention of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular and of cerebrovascular diseases or conditions associated with platelet aggregation, including thrombosis in humans and other mammals.

  本发明涉及式(I)化合物，其中R1、R2、R4、R5、Ra、Rb、n、W和Z如申请中所定义，它们的制备以及它们作为P2Y12受体拮抗剂用于治疗和/或预防外周血管、内脏血管、肝脏血管和肾脏血管、心血管和脑血管疾病或与血小板聚集相关的状况的应用，包括人类和其他哺乳动物中的血栓。
• [EN] THIAZOLE DERIVATIVES AND THEIR USE AS P2Y12 RECEPTOR ANTAGONISTS<br/>[FR] DÉRIVÉS DE THIAZOLE ET LEUR UTILISATION COMME ANTAGONISTES DES RÉCEPTEURS P2Y12
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2010122504A1

  公开（公告）日：2010-10-28

  The present invention relates to thiazole derivatives of Formula (I) and their use as P2Y12 receptor antagonists in the treatment and/or prevention of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular and of cerebrovascular diseases or conditions associated with platelet aggregation, including thrombosis in humans and other mammals.

  本发明涉及式(I)的噻唑衍生物及其作为P2Y12受体拮抗剂用于治疗和/或预防外周血管、内脏血管、肝脏血管和肾脏血管、心血管和脑血管疾病或与血小板聚集相关的状况，包括人类和其他哺乳动物中的血栓。
• [EN] PYRAZOLIDINEDIONE DERIVATIVES AND THEIR USE AS PLATELET AGGREGATION INHIBITORS<br/>[FR] DERIVES DE PYRAZOLIDINEDIONE ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE L'AGREGATION DES PLAQUETTES
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2005002574A1

  公开（公告）日：2005-01-13

  Pyrazolidinedione derivatives of the general formula (I), wherein R1 is hydrogen, optionally substituted alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl; and R2 is aryl or heteroaryl; tautomers thereof; geometric isomers thereof and tautomers of these geometric isomers, including mixtures of individual compounds of formula (I), or tautomers thereof, and their geometric isomers, or tautomers thereof; pharmaceutically acceptable acid addition salts of compounds which are basic; pharmaceutically acceptable salts of compounds containing acidic groups with bases; pharmaceutically acceptable esters of compounds containing hydroxy or carboxy groups; prodrugs of compounds in which a prodrug forming group is present; as well as hydrates or solvates thereof; are active as platelet adenosine diphosphate receptor antagonists and can be used for the prevention and/or treatment of peripheral vascular, of visceral-, hepaticand renal-vascular, of cardiovascular and of cerebrovascular diseases or conditions associated with platelet aggregation, particularly thrombosis, and, respectively, for the manufacture of corresponding medicaments. Some, albeit not all, of the compounds of the above formula (I) are novel.

  一般公式（I）的吡唑烷二酮衍生物，其中R1是氢，可选地取代烷基，环烷基，芳基，芳烷基，杂芳基或杂芳烷基；R2是芳基或杂芳基；其互变异构体；其几何异构体及这些几何异构体的互变异构体，包括公式（I）的单个化合物的混合物，或其互变异构体，及其几何异构体，或其互变异构体；药物可接受的酸加成盐基本化合物；含有酸性基团的化合物与碱的药物可接受盐；含有羟基或羧基的化合物的药物可接受酯；以及存在前药形成基团的化合物的前药；以及它们的 hydrates 或 solvates；作为血小板二磷酸腺苷受体拮抗剂活性，可用于预防或治疗外周血管疾病，内脏、肝脏和肾脏血管疾病，心血管疾病和脑血管疾病或与血小板聚集相关的病症，尤其是血栓症，并且分别用于制造相应的药物。上述公式（I）中的一些化合物是新颖的，但并非全部。