pyridinium (chloromethylene)bisphosphonate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: pyridinium (chloromethylene)bisphosphonate
• 英文别名: [Chloro(phosphono)methyl]-hydroxyphosphinate;pyridin-1-ium；[chloro(phosphono)methyl]-hydroxyphosphinate;pyridin-1-ium
• 化学式: CH₅ClO₆P₂*C₅H₅N
• 分子量: 289.549
• InChiKey: BSIFOWFAZYNRDA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.95
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  128
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  pyridinium (chloromethylene)bisphosphonate 在 sodium perchlorate 、 三乙胺 、 zinc(II) chloride 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 1.0h， 生成 P¹,P⁴-di-(2-iodo-5'-adenosine)-P¹,P⁴-dithio-P²,P³-chloromethylenetetraphosphate sodium salt
  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：

  吡啶 、 tetra-isopropyl monochloromethylene bisphosphonate 在 盐酸 作用下， 以 水 、 乙醇 为溶剂， 反应 4.0h， 以97.4%的产率得到pyridinium (chloromethylene)bisphosphonate
  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

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)。
• P¹,P²-Diimidazolyl derivatives of pyrophosphate and bis-phosphonates – synthesis, properties, and use in preparation of dinucleoside tetraphosphates and analogs
  作者：Ivan B. Yanachkov、Edward J. Dix、Milka I. Yanachkova、George E. Wright

  DOI：10.1039/c0ob00542h

  日期：——

  P 1,P2-Diimidazolyl derivatives of pyrophosphate and halomethylene-bis-phosphonates have been synthesized and characterized, and the mechanism of their formation was studied. These reagents enable synthesis of dinucleoside tetraphosphates and tetraphosphonates conveniently and in high yields.

  合成并表征了焦磷酸盐和卤代亚甲基双膦酸盐的P 1、P 2 -二咪唑基衍生物，并研究了它们的形成机理。这些试剂能够方便且高产率地合成二核苷四磷酸盐和四膦酸盐。
• NOVEL ANTITHROMBOTIC DIADENOSINE TETRAPHOSPHATES AND RELATED ANALOGS
  申请人：Glsynthesis Inc.

  公开号：EP2364086A1

  公开（公告）日：2011-09-14
• US8575127B2
  申请人：——

  公开号：US8575127B2

  公开（公告）日：2013-11-05