坎格瑞洛中间体3 | 847460-53-1

• 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: 坎格瑞洛中间体3
• 英文名称: N-[2-(methylthio)ethyl]-2-[(3,3,3-trifluoropropyl)thio]-5'-adenylic acid
• 英文别名: [(2R,3S,4R,5R)-3,4-dihydroxy-5-[6-(2-methylsulfanylethylamino)-2-(3,3,3-trifluoropropylsulfanyl)purin-9-yl]oxolan-2-yl]methyl dihydrogen phosphate
• CAS: 847460-53-1
• 化学式: C₁₆H₂₃F₃N₅O₇PS₂
• 分子量: 549.489
• InChiKey: KVLRBRZHCOVMNX-IDTAVKCVSA-N

物化性质

• 熔点：
  >135°C (dec.)
• 沸点：
  848.4±75.0 °C(Predicted)
• 密度：
  1.85±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  34
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  223
• 氢给体数：
  5
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  氯屈膦酸三正丁胺盐 、 坎格瑞洛中间体3 在 吡啶 、 甲醇 、 三正丁胺 、 N,N'-羰基二咪唑 作用下， 生成 坎格雷洛
  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：

  坎格雷洛杂质 在 sodium hydroxide 、 磷酸三乙酯 、 sodium acetate 、 sodium hydride 、 碳酸氢钠 、 三氯氧磷 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 37.25h， 生成 坎格瑞洛中间体3
  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

• Process for preparation of cangrelor tetrasodium and intermediate therefor
  申请人：ScinoPharm Taiwan, Ltd.

  公开号：US20190241606A1

  公开（公告）日：2019-08-08

  A process for preparing cangrelor tetrasodium comprising: a) reacting a compound of formula M1 with morpholine to form a compound of formula M2; and b) reacting the compound of formula M2 with clodronic acid to provide cangrelor tetrasodium

  制备曲格列酮四钠的方法包括：a)将化合物M1与吗啉反应，形成化合物M2；b)将化合物M2与氯膦酸反应，得到曲格列酮四钠。
• 一种坎格雷洛中间体的纯化方法
  申请人：上海博志研新药物技术有限公司

  公开号：CN106674322B

  公开（公告）日：2019-04-16

  本发明公开了一种坎格雷洛中间体的纯化方法。本发明提供了一种坎格雷洛中间体I的纯化方法，包括步骤1：将坎格雷洛中间体I粗品与有机溶剂形成的混合物与碱式盐或氨水进行反应后，萃取，得到水相；步骤2：将水相除去水，后加入醇类溶剂，过滤或离心得滤饼；步骤3：水中，将滤饼调节pH至2‑3，过滤或离心，得到滤饼；步骤4：醇类溶剂中，将滤饼调节pH至7‑8，过滤得到坎格雷洛中间体I。本发明的纯化方法避免使用昂贵、操作繁琐及纯化时间长的阳离子交换树脂和反向硅胶分离方法、操作简单、反应时间短、收率高、制得的产品纯度高，HPLC纯度大于99.0％，生产成本低、适合于工业化生产。
• [EN] N-ALKYL-2-SUBSTITUTED ATP ANALOGUES<br/>[FR] ANALOGUES D'ADENOSINE TRIPHOSPHATE (ATB) SUBSTITUES EN POSITION 2 PAR N-ALKYLE
  申请人：ASTRA PHARMACEUTICALS LIMITED

  公开号：WO1994018216A1

  公开（公告）日：1994-08-18

  (EN) There are disclosed compounds of formula (I) wherein R1 and R2 independently represent hydrogen or halogen, R3 and R4 independently represent phenyl, or alkyl C1-6 optionally substituted by one or more substituents selected from OR5, alkylthio C1-6, NR6R7, phenyl, COOR8 and halogen, R5, R6, R7 and R8 independently represent hydrogen or alkyl C1-6, and X represents an acidic moiety, and pharmaceutically acceptable salts thereof. Processes for their production and pharmaceutical compositions and methods of treatment involving their use are also described.(FR) L'invention se rapporte à des composés de la formule (I) dans laquelle R1 et R2 représentent indépendamment hydrogène ou halogène, R3 et R4 représentent indépendamment phényle ou alkyle C1-6 éventuellement substitués par un ou plusieurs substituants choisis entre OR5, alkylthio C1-6, NR6R7, phényle, COOR8 et halogène, R5, R6, R7 et R8 représentent indépendamment hydrogène ou alkyle C1-6, et X représente une fraction acide. L'invention se rapporte également à des sels pharmaceutiquement acceptables de ces composés. Des procédés de production, ainsi que des compositions pharmaceutiques et des procédés de traitement comprenant l'utilisation de ces dernières sont également décrits.

  该文献介绍了公式（I）的化合物，其中R1和R2独立地表示氢或卤素，R3和R4独立地表示苯基或C1-6烷基，该烷基可以选择地被一个或多个取代基所取代，所述取代基选自OR5，C1-6烷基硫基，NR6R7，苯基，COOR8和卤素。R5、R6、R7和R8独立地表示氢或C1-6烷基，X表示酸性基团，以及其药物可接受的盐。该文献还描述了它们的生产过程、药物组合物和涉及其使用的治疗方法。
• N-alkyl-2-substituted ATP analogues and administration to inhibit
  申请人：Astra Pharmaceuticals Ltd.

  公开号：US05721219A1

  公开（公告）日：1998-02-24

  There are disclosed compounds of formula I, ##STR1## wherein R.sup.1 and R.sup.2 independently represent hydrogen or halogen, R.sup.3 and R.sup.4 independently represent phenyl, or alkyl C.sub.1-6, optionally substituted by one or more substituents selected from OR.sup.5, alkylthio C.sub.1-6, NR.sup.6 R.sup.7, phenyl, COOR.sup.8 and halogen, R.sup.5, R.sup.6, R.sup.7 and R.sup.8 independently represent hydrogen or alkyl C.sub.1-6, and X represents an acidic moiety, and pharmaceutically acceptable salts thereof. Processes for their production and pharmaceutical compositions and methods of treatment involving their use are also described.

  公开了化合物I的结构，其中R1和R2独立地表示氢或卤素，R3和R4独立地表示苯基或烷基C1-6，可选地被一个或多个取代基所取代，所述取代基选择自OR5、烷基硫基C1-6、NR6R7、苯基、COOR8和卤素，R5、R6、R7和R8独立地表示氢或烷基C1-6，X表示酸性基团，以及其药学上可接受的盐。还描述了它们的制备过程和涉及其使用的药物组合物和治疗方法。
• METHOD OF SCREENING ANTIPLATELET
  申请人：YAMANOUCHI PHARMACEUTICAL CO. LTD.

  公开号：EP1331228A1

  公开（公告）日：2003-07-30

  A screening tool for an antiplatelet agent wherein the tool is a human ADP receptor P2TAC protein, a variation functionally equivalent thereto, or a homologous protein thereof, and a screening tool for an antiplatelet agent wherein the tool is a transformant which is transformed with an expression vector comprising a DNA encoding the protein and is expressing the polypeptide are disclosed. Further, a method for detecting an ADP receptor P2TAC ligand, antagonist, or agonist by using the screening tool for an antiplatelet agent, and a method for screening an antiplatelet agent by the detecting method are disclosed.

  本发明公开了一种抗血小板药物的筛选工具，其中该工具是人ADP受体P2TAC蛋白、其功能等同的变体或其同源蛋白；还公开了一种抗血小板药物的筛选工具，其中该工具是用包含编码该蛋白的DNA的表达载体转化并表达多肽的转化体。此外，还公开了一种通过使用该抗血小板药剂筛选工具检测ADP受体P2TAC配体、拮抗剂或激动剂的方法，以及一种通过该检测方法筛选抗血小板药剂的方法。