2-甲基硫代二磷酸腺苷 | 34983-48-7

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 中文名称: 2-甲基硫代二磷酸腺苷
• 英文名称: 2-methylthio adenosine 5'-diphosphate
• 英文别名: 2MeSADP；2-methylthioadenosine diphosphate；2-methyl-thio-ADP；2-Methylthio-adenosine-5'-diphosphate；[(2R,3S,4R,5R)-5-(6-amino-2-methylsulfanylpurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphono hydrogen phosphate
• CAS: 34983-48-7
• 化学式: C₁₁H₁₇N₅O₁₀P₂S
• 分子量: 473.297
• InChiKey: WLMZTKAZJUWXCB-KQYNXXCUSA-N

物化性质

• 沸点：
  936.1±75.0 °C(Predicted)
• 密度：
  2.35±0.1 g/cm3(Predicted)
• 溶解度：
  在水中的溶解度35 mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  -3.8
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  258
• 氢给体数：
  6
• 氢受体数：
  15

安全信息

• 安全说明：
  S22,S24/25
• WGK Germany：
  3

反应信息

• 作为反应物：
  描述：

  2-甲基硫代二磷酸腺苷 、 1-(4,5-dimethoxy-2-nitrophenyl)diazoethane 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以66%的产率得到P¹-2-(methylthio)adenosyl-P²-(RS)-1-(4,5-dimethoxy-2-nitrophenyl)ethyl pyrophosphate
  参考文献：
  名称：

  Caged agonist of P2Y1 and P2Y12 receptors for light-directed facilitation of platelet aggregation

  摘要：

  We have prepared a caged form (MRS2703) of a potent dual agonist of the P2Y(1) and P2Y(12) nucleotide receptors, 2-MeSADP, by blocking the p-phosphate group with a 1-(3,4-dimethyloxyphenyl)eth-1-yl phosphoester. Although MRS2703 is itself inactive at human P2Y(1) and P2Y(12) receptors expressed heterologously in 1321N1 astrocytoma cells or in washed human platelets, this derivative readily regenerates the parent agonist upon mild irradiation with long-wave UV light (360 nm). The functional effect of the regenerated agonist was demonstrated by a rise in intracellular calcium mediated by either P2Y(1) or P2Y(12) receptors in transfected cells. Washed human platelets exposed to a solution of MRS2703 were induced to aggregate upon UV irradiation. At 1.0 mu M MRS2703, full aggregation was achieved within 1 min of irradiation. Thus, this caged nucleotide promises to be a useful probe for potent P2Y receptor activation with light-directed spatial and temporal control. Published by Elsevier Inc.

  DOI：

  10.1016/j.bcp.2007.10.037
• 作为产物：
  描述：

  2-methylthio-ATP 、 alkaline earth salt of/the/ methylsulfuric acid 在 purified ectonucleosidase from the bovine aorta 作用下， 以 水 为溶剂， 反应 0.17h， 生成 2-甲基硫代二磷酸腺苷
  参考文献：
  名称：

  Hydrolysis of P2-Purinoceptor agonists by a purified ectonucleotidase from the bovine aorta, the ATP-diphosphohydrolase

  摘要：

  Pharmacologists are becoming more and more aware of the possibility that certain ATP analogues currently used to classify the P-2-purinoceptors are dephosphorylated by ectonucleotidases. In this study, we provide evidence that in the vascular system, these purine analogues are hydrolysed by an ATP-diphosphohydrolase (ATPDase). This enzyme is known as the major plasma membrane nucleotidase of endothelial and smooth muscle cells, and is believed to dephosphorylate extracellular triphospho- and diphosphonucleosides. Assays were conducted with a purified ATPDase from smooth muscle cells of bovine aorta. At a concentration of 250 mu M, adenosine 5'-(alpha,beta-methylene) triphosphonate (alpha,beta-metATP), adenosine 5'-(beta,gamma-methylene) triphosphonate (beta,gamma-metATP), adenosine 5'-(alpha,beta-methylene) diphosphonate (alpha,beta-metADP), adenylyl 5'-(beta,gamma-imido) diphosphonate (beta,gamma-imidoATP) and adenosine 5'-O-(2-thiodiphosphate) (ADP beta S) all resisted dephosphorylation, whereas 2-chloroadenosine triphosphate (2-chloroATP), 2-methylthioadenosine triphosphate (2-MeSATP) and 8-bromoadenosine triphosphate (8-bromoATP) were hydrolysed at 99, 63, and 20% of the rate of ATP hydrolysis, respectively. All the non-hydrolysable analogues tested, except alpha,beta-metADP, competed with ATP and ADP for the ATPDase catalytic site, reducing their hydrolysis by 35-50%. Apparent K-m values for ATP and ADP were estimated at 14.1 and 12.0 mu M, respectively, whereas apparent K-m and K-i values for the purine analogues ranged from 12 to 28 mu M These results strongly support the view that (1) the ATPDase is expected to reduce substantially the P-2-response induced by ATP, ADP, and some hydrolysable agonists; and (2) by competing with the hydrolysis of endogenously released ATP and ADP, non-hydrolysable analogues could alter the amplitude or direction of the cellular response induced by these natural substrates.

  DOI：

  10.1016/0006-2952(96)00086-x

文献信息

• Piperazine and homopiperazine compounds
  申请人：Millennium Pharmaceuticals, Inc.

  公开号：US20030153556A1

  公开（公告）日：2003-08-14

  Compounds are provided having a piperazine or homopiperazine ring which are useful in the treatment of thrombosis.

  提供了具有哌嗪或同源哌嗪环的化合物，这些化合物在治疗血栓症方面很有用。
• Platelet ADP receptor inhibitors
  申请人：——

  公开号：US20020077486A1

  公开（公告）日：2002-06-20

  Novel compounds of formulae (I) to (VIII), which more particularly include sulfonylurea derivatives, sulfonylthiourea derivatives, sulfonylguanidine derivatives, sulfonylcyanoguanidine derivatives, thioacylsulfonamide derivatives, and acylsulfonamide derivatives which are effective platelet ADP receptor inhibitors. These derivatives may be used in various pharmaceutical compositions, and are particularly effective for the prevention and/or treatment of cardiovascular diseases, particularly those diseases related to thrombosis. The invention also relates to a method for preventing or treating thrombosis in a mammal comprising the step of administering a therapeutically effective amount of a compound of formulae (I) to (VIII), or a pharmaceutically acceptable salt thereof.

  化合物的新颖结构式（I）至（VIII），其中更特别包括磺酰脲衍生物、磺酰硫脲衍生物、磺酰胍衍生物、磺酰氰胍衍生物、硫代酰基磺酰胺衍生物和酰基磺酰胺衍生物，这些衍生物是有效的血小板ADP受体抑制剂。这些衍生物可用于各种药物组合中，特别适用于预防和/或治疗心血管疾病，特别是与血栓形成相关的疾病。该发明还涉及一种用于预防或治疗哺乳动物体内血栓形成的方法，包括给予化合物的治疗有效量的步骤，该化合物为结构式（I）至（VIII）中的一种，或其药学上可接受的盐。
• Substituted 2H-1,3-benzoxazin-4(3H)-ones
  申请人：Scarborough M. Robert

  公开号：US20060069093A1

  公开（公告）日：2006-03-30

  Substituted benzoxazin-4(3H)-ones are provided which are useful for treating thrombosis and for reducing the likelihood and/or severity of a secondary ischemic event in a patient.

  提供了对治疗血栓形成和减少患者发生继发性缺血事件的可能性和/或严重程度有用的取代苯并噁唑啉-4(3H)-酮。
• [EN] SUBSTITUTED ISOQUINOLINONES<br/>[FR] ISOQUINOLEINONES SUBSTITUEES
  申请人：PORTOLA PHARM INC

  公开号：WO2005035520A1

  公开（公告）日：2005-04-21

  Isoquinolinone compounds are provided that are useful for the inhibition of ADP-platelet aggregation, particularly in the treatment of thrombosis and thrombosis related conditions or disorders.

  提供了对异喹啉酮化合物，这些化合物对于抑制ADP-血小板聚集特别有用，尤其在治疗血栓形成和与血栓形成相关的疾病或疾病时。
• 2-PHENYL-6-AMINOCARBONYL-PYRIMIDINE DERIVATIVES AND THEIR USE AS P2Y12 RECEPTOR
  申请人：Caroff Eva

  公开号：US20090291962A1

  公开（公告）日：2009-11-26

  The invention relates to 2-phenyl-6-aminbcarbonyl-pyrimidinc derivatives and their use as P2Y 12 receptor antagonists in the treatment and/or prevention and/or treatment 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. Formula (1).

  这项发明涉及2-苯基-6-氨基羰基嘧啶衍生物及其作为P2Y12受体拮抗剂在治疗和/或预防和/或治疗外周血管、内脏-、肝脏和肾脏血管、心血管和脑血管疾病或与血小板聚集有关的疾病或病况的用途，包括人类和其他哺乳动物中的血栓形成。公式（1）。