2-amino-9-(2-deoxy-pentofuranosyl)-1,9-dihydro-purine-6-thione | 789-61-7

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 2-amino-9-(2-deoxy-pentofuranosyl)-1,9-dihydro-purine-6-thione
• 英文别名: alpha-2'-Deoxythioguanosine；2-amino-9-[4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3H-purine-6-thione
• CAS: 789-61-7；2133-81-5
• 化学式: C₁₀H₁₃N₅O₃S
• 分子量: 283.311
• InChiKey: SCVJRXQHFJXZFZ-UHFFFAOYSA-N

物化性质

• 熔点：
  190-192 °C
• 沸点：
  709.1±70.0 °C(Predicted)
• 密度：
  2.02±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO（少量溶解）、DMF（少量溶解）、甲醇（少量，加热）、水（非常少量）

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  150
• 氢给体数：
  4
• 氢受体数：
  5

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

制备方法与用途

生物活性

6-thio-dG（β-TGdR）是一种核苷类似物，并且是端粒酶底物。

靶点

DNA/RNA合成

体外研究

在端粒酶阳性的癌细胞和表达hTERT的人纤维细胞中，6-Thio-dG诱导了端粒功能障碍，导致端粒逐渐缩短。这种核苷类似物在测试的癌细胞中抑制了细胞活性，IC50值为0.7-2.9 μM。

体内研究

在注射A549肺癌异种移植瘤的小鼠中，6-Thio-dG（2 mg/kg，腹腔注射）通过诱导端粒功能障碍增加了A549细胞的肿瘤发生。

文献信息

• COATING FOR A MEDICAL DEVICE HAVING AN ANTI-THROMBOTIC CONJUGATE
  申请人：Zhao Jonathon Z.

  公开号：US20080200421A1

  公开（公告）日：2008-08-21

  A conjugate between an anti-thrombotic agent and a bioabsorbable polymer is provided. In addition, a method is provided for applying a coating comprising an anti-thrombotic agent and a bioabsorbable polymer conjugate to at least a portion of an implantable device to prevent or reduce the formation of thrombosis on the surface of the device. A first or sub-layer of the coating is prepared by mixing a polymeric material and a biologically active agent with a solvent, thereby forming a homogeneous solution. A second or outer layer comprises an anti-thrombotic heparin-bioabsorbable polymer conjugate. This coating may be applied over the inner drug-containing layers using, for example, a dip coating or spray coating process. After drying, the anti-thrombotic heparin bioabsorbable polymer conjugate remains in the outer layer of the coating, allowing agent from the inner layer to be eluted there through. In addition, the outmost layer prevents the formation of thrombosis, and also serves to modulate the release kinetics of the agent(s) contained within an inner layer(s) of the coating.

  提供了一种抗血栓药物与可生物吸收聚合物的共轭物。此外，提供了一种方法，用于将包含抗血栓药物和可生物吸收聚合物共轭物的涂层应用于可植入设备的至少部分表面，以预防或减少设备表面的血栓形成。涂层的第一或次表层通过将聚合物材料和生物活性剂与溶剂混合制备而成，从而形成均匀溶液。第二或外层包括抗血栓肝素-可生物吸收聚合物共轭物。该涂层可以通过浸涂或喷涂工艺覆盖在内部含药层上。干燥后，抗血栓肝素可生物吸收聚合物共轭物保留在涂层的外层，使内层的药物能够通过其释放。此外，最外层防止了血栓形成，并且还用于调节涂层内部层中所含药物的释放动力学。
• PH-SENSITIVE POLYMERIC MICELLES FOR DRUG DELIVERY
  申请人：Kim Dongin

  公开号：US20100009926A1

  公开（公告）日：2010-01-14

  Mixed micelles containing poly(L-histidine-co-phenylalanine)-poly(ethylene glycol) block copolymer and poly(L-lactic acid)-poly(ethylene glycol) block copolymer are a pH-sensitive drug carrier that release the drug in an acidic microenvironment, but not in the blood. Since the microenvironment of solid tumors is acidic, these mixed micelles are useful for treating cancer, including those cancers exhibiting multidrug resistance. Targeting ligands, such as folate, can also be attached to the mixed micelles for enhancing drug delivery into cells. Methods of treating a warm-blooded animal with such a drug are disclosed.

  含有聚(L-组氨酸-co-苯丙氨酸)-聚乙二醇嵌段共聚物和聚(L-乳酸)-聚乙二醇嵌段共聚物的混合胶束是一种pH敏感的药物载体，可以在酸性微环境中释放药物，但不会在血液中释放。由于固体肿瘤的微环境是酸性的，因此这些混合胶束对于治疗癌症，包括表现出多药耐药性的癌症，非常有用。靶向配体，如叶酸，也可以附着在混合胶束上，以增强药物输送到细胞内。公开了使用这种药物治疗温血动物的方法。
• THERAPEUTIC BENEFIT OF SUBOPTIMALLY ADMINISTERED CHEMICAL COMPOUNDS
  申请人：BROWN Dennis M.

  公开号：US20160045502A1

  公开（公告）日：2016-02-18

  The present invention describes methods and compositions for improving the therapeutic efficacy of therapeutic agents previously limited by suboptimal therapeutic performance by either improving efficacy as monotherapy or reducing side effects. Such methods and compositions are particularly applicable to mustard-based alkylating agents such as uracil mustard and analogs, derivatives, or prodrugs thereof, including 6-methyluracil mustard and 6-ethyluracil mustard.

  本发明描述了一种改善先前受到治疗性能不佳限制的治疗剂的治疗效果的方法和组合物，通过改善单药疗法的功效或减少副作用。这种方法和组合物特别适用于芥子碱基烷基化剂，例如尿嘧啶芥和其类似物、衍生物或前药，包括6-甲基尿嘧啶芥和6-乙基尿嘧啶芥。
• A Coating for a Medical Device Having an Anti-Thrombotic Conjugate
  申请人：Cordis Corporation

  公开号：EP1961434A2

  公开（公告）日：2008-08-27

  A conjugate between an anti-thrombotic agent and a bioabsorbable polymer is provided. In addition, a method is provided for applying a coating comprising an anti-thrombotic agent and a bioabsorbable polymer conjugate to at least a portion of an implantable device to prevent or reduce the formation of thrombosis on the surface of the device. A first or sub-layer of the coating is prepared by mixing a polymeric material and a biologically active agent with a solvent, thereby forming a homogeneous solution. A second or outer layer comprises an anti-thrombotic heparin-bioabsorbable polymer conjugate. This coating may be applied over the inner drug-containing layers using, for example, a dip coating or spray coating process. After drying, the anti-thrombotic heparin bioabsorbable polymer conjugate remains in the outer layer of the coating, allowing agent from the inner layer to be eluted there through. In addition, the outmost layer prevents the formation of thrombosis, and also serves to modulate the release kinetics of the agent(s) contained within an inner layer(s) of the coating.

  本发明提供了一种抗血栓药物与生物可吸收聚合物的共轭物。此外，还提供了一种方法，用于将包含抗血栓药剂和生物可吸收聚合物共轭物的涂层涂在植入式装置的至少一部分上，以防止或减少装置表面血栓的形成。涂层的第一层或底层是通过将聚合物材料和生物活性剂与溶剂混合，从而形成均匀的溶液来制备的。第二层或外层包括抗血栓肝素-生物可吸收聚合物共轭物。该涂层可通过浸涂或喷涂等工艺涂覆在含药内层上。干燥后，抗血栓肝素-生物可吸收聚合物共轭物仍留在涂层外层，使内层的药剂通过该层洗脱出来。此外，最外层可防止血栓形成，还可调节涂层内层所含药剂的释放动力学。
• A medical device coating having an anti-thrombotic conjugate
  申请人：Cordis Corporation

  公开号：EP1987851A2

  公开（公告）日：2008-11-05

  A method for applying a coating comprising a comb-type anti-thrombotic conjugate to at least a portion of an implantable device to prevent or reduce the formation of thrombosis on the surface of the device, involves preparing a first or sub-layer of the coating by mixing a polymeric material and a biologically active agent with a solvent, thereby forming a homogeneous solution. A second or outer layer comprising a comb-type anti-thrombotic conjugate is applied over the inner drug-containing layers using, for example, a dip coating or spray coating process. Alternatively the comb-type antithrombotic conjugate may be used as a matrix material to encapsulate a pharmaceutical agent to form microspheres or nanospheres before depositing the microspheres or nanospheres onto a medical device.

  一种将包含梳型抗血栓共轭物的涂层应用于植入式装置的至少一部分，以防止或减少装置表面血栓形成的方法，包括通过将聚合物材料和生物活性剂与溶剂混合，从而形成均匀溶液，制备涂层的第一层或亚层。第二层或外层包含梳状抗血栓结合物，通过浸涂或喷涂等工艺涂在含药物的内层上。梳状抗血栓共轭物也可用作基质材料，在将微球或纳米球沉积到医疗设备上之前，将药剂封装成微球或纳米球。