2-Carboxymethylthio-2-methyltetrahydrofuran | 125488-67-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 2-Carboxymethylthio-2-methyltetrahydrofuran
• 英文别名: 2-(2-methyloxolan-2-yl)sulfanylacetic acid
• CAS: 125488-67-7
• 化学式: C₇H₁₂O₃S
• 分子量: 176.236
• InChiKey: YLBIBZGPDFTRKC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  11
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  71.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-Carboxymethylthio-2-methyltetrahydrofuran 在 BH₃ 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 2-Hydroxyethylthio-2-methyltetrahydrofuran
  参考文献：
  名称：

  Metal radionuclide chelating compounds for improved chelation kinetics

  摘要：

  本发明提供了金属螯合化合物，用于形成螯合物和螯合靶向试剂共轭物的螯合化合物，以及制备和使用这些组合物的方法。螯合化合物包括两个氮原子和三个硫原子（“N.sub.2S.sub.3”），两个氮原子和四个硫原子（“N.sub.2S.sub.4”）或三个氮原子和三个硫原子（“N.sub.3S.sub.3”）。能够被化合物螯合的金属和金属氧化物包括放射性核素，如.sup.99mTc和.sup.186/188Re。螯合靶向试剂共轭物的靶向试剂部分包括抗体、肽、激素、酶和生物反应修饰剂。本发明提供了制备共轭物的方法，包括在连接到靶向试剂之前或之后向螯合化合物中添加金属或金属氧化物。本发明的另一个方面提供了用于制备放射性药物的螯合靶向试剂共轭物的套件。本发明的另一个方面提供了将螯合靶向试剂共轭物用于诊断和治疗目的的方法，例如检测目标位点和向该位点输送放射性核素。

  公开号：

  US04988496A1
• 作为产物：
  描述：

  2,3-二氢-5-甲基呋喃 、 对甲苯磺酸一水合物 、 巯基乙酸 以 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 生成 2-Carboxymethylthio-2-methyltetrahydrofuran
  参考文献：
  名称：

  Metal radionuclide chelating compounds for improved chelation kinetics

  摘要：

  本发明提供了金属螯合化合物，用于形成螯合物和螯合靶向试剂共轭物的螯合化合物，以及制备和使用这些组合物的方法。螯合化合物包括两个氮原子和三个硫原子（“N.sub.2S.sub.3”），两个氮原子和四个硫原子（“N.sub.2S.sub.4”）或三个氮原子和三个硫原子（“N.sub.3S.sub.3”）。能够被化合物螯合的金属和金属氧化物包括放射性核素，如.sup.99mTc和.sup.186/188Re。螯合靶向试剂共轭物的靶向试剂部分包括抗体、肽、激素、酶和生物反应修饰剂。本发明提供了制备共轭物的方法，包括在连接到靶向试剂之前或之后向螯合化合物中添加金属或金属氧化物。本发明的另一个方面提供了用于制备放射性药物的螯合靶向试剂共轭物的套件。本发明的另一个方面提供了将螯合靶向试剂共轭物用于诊断和治疗目的的方法，例如检测目标位点和向该位点输送放射性核素。

  公开号：

  US04988496A1

文献信息

• Methods for introducing a sulfhydryl amino or hydroxyl groups to a
  申请人：NeoRx Corporation

  公开号：US05017693A1

  公开（公告）日：1991-05-21

  The present invention provides cleavable conjugates whose linkers contain a labile bond that is cleavable under a variety of mild conditions, including weakly acidic. Since the agent may be bonded directly to the linker, cleavage can result in release of native agent. The invention also provides methods for producing cleavable conjugates. Preferred agents include drugs, toxins, biological response modifiers, radiodiagnostic compounds, radiotherapeutic compounds, and derivatives thereof. The targeting molecule employed in the invention may be an intact molecule, a fragment thereof, or a functional equivalent thereof. In a particularly preferred embodiment, the targeting molecule is a monoclonal antibody directed towards a tumor-associated antigen in man. The invention further provides methods for delivering to the cytoplasm of target cell an agent free of its targeting molecular carrier. A diagnostically therapeutically effective dose of a cleavable conjugate is administered to a warm-blooded animal such as man. Another aspect of the invention provides methods for isolating a compound. The compound binds covalently to a solid phase which has been derivatized with the linkers described above and is released in native form by a variety of mild conditions. An additional aspect of the invention provides methods for introducing into a compound a free sulfhydryl, amino, or hydroxyl group by use of reagents structurally related to the linkers described above. Preferred uses of the method are to add a free amino or a free sulfhydryl group to a protein, such as an antibody, or a drug.

  本发明提供了可裂解的结合物，其连接剂包含一种在多种温和条件下可裂解的不稳定键，包括弱酸性条件。由于药物可以直接与连接剂结合，因此裂解可以导致原有药物的释放。本发明还提供了制备可裂解结合物的方法。首选药物包括药品、毒素、生物反应修饰剂、放射性诊断化合物、放射性治疗化合物及其衍生物。本发明所采用的靶向分子可以是完整分子、其片段或其功能等效物。在一个特别优选的实施例中，靶向分子是针对人类肿瘤相关抗原的单克隆抗体。本发明还提供了将不带有其靶向分子载体的药物递送到靶细胞的细胞质中的方法。将可裂解结合物的诊断治疗有效剂量给予温血动物，例如人。本发明的另一个方面提供了分离化合物的方法。该化合物与已用上述连接剂衍生化的固相共价结合，并可通过多种温和条件以原有形式释放。本发明的另一个方面提供了使用与上述连接剂结构相关的试剂将自由巯基、氨基或羟基引入化合物的方法。所述方法的首选用途是向蛋白质（如抗体或药物）添加自由氨基或自由巯基基团。
• Cleavable conjugates for the delivery and release of agents in native
  申请人：NeoRx Corporation

  公开号：US05563250A1

  公开（公告）日：1996-10-08

  The present invention provides cleavable conjugates whose linkers contain a labile bond that is cleavable under a variety of mild conditions, including weakly acidic. Since the agent may be bonded directly to the linker, cleavage can result in release of native agent. The invention also provides methods for producing cleavable conjugates. Preferred agents include drugs, toxins, biological response modifiers, radiodiagnostic compounds, radiotherapeutic compounds, and derivatives thereof. The targeting molecule employed in the invention may be an intact molecule, a fragment thereof, or a functional equivalent thereof. In a particularly preferred embodiment, the targeting molecule is a monoclonal antibody directed towards a tumor-associated antigen in man. The invention further provides methods for delivering to the cytoplasm of a target cell an agent free of its targeting molecule carrier. A diagnostically/therapeutically effective dose of a cleavable conjugate is administered to a warm-blooded animal such as man.

  本发明提供了可裂解的共轭物，其连接剂包含易裂解的键，可在多种温和条件下（包括弱酸性）被裂解。由于制剂可以直接与连接剂结合，因此裂解可以释放原生制剂。本发明还提供了制备可裂解共轭物的方法。首选制剂包括药物、毒素、生物反应修饰剂、放射诊断化合物、放射治疗化合物及其衍生物。本发明所使用的靶向分子可以是完整分子、其片段或其功能等效物。在一种特别优选的实施例中，靶向分子是针对人类肿瘤相关抗原的单克隆抗体。本发明还提供了将不带有其靶向分子载体的制剂输送到靶细胞的细胞质中的方法。可裂解的共轭物的诊断/治疗有效剂量被给予温血动物，例如人类。
• Methods for isolating compounds using cleavable linker bound matrices
  申请人：NeoRx Corporation

  公开号：US05141648A1

  公开（公告）日：1992-08-25

  The present invention provides cleavable conjugates whose linkers contain a labile bond that is cleavable under a variety of mild conditions, including weakly acidic. Since the agent may be bonded directly to the linker, cleavage can result in release of native agent. The invention also provides methods for producing cleavable conjugates. Preferred agents include drugs, toxins, biological response modifiers, radiodiagnostic compounds, radiotherapeutic compounds, and derivatives thereof. The targeting molecule employed in the invention may be an intact molecule, a fragment thereof, or a functional equivalent thereof. In a particularly preferred embodiment, the targeting molecule is a monoclonal antibody directed towards a tumor-associated antigen in man. The invention further provides methods for delivering to the cytoplasm of a target cell an agent free of its targeting molecule carrier. A diagnostically/therapeutically effective dose of a cleavable conjugate is administered to a warm-blooded animal such as man. Another aspect of the invention provides methods for isolating a compound. The compound binds covalently to a solid phase which has been derivatized with the linkers described above and is released in native form by a variety of mild conditions. An additional aspect of the invention provides methods for introducing into a compound a free sulfhydryl, amino, or hydroxyl group by use of reagents structurally related to the linkers described above. Preferred uses of the method are to add a free amino or a free sulfhydryl group to a protein, such as an antibody, or a drug.

  本发明提供了可裂解的共轭物，其连接剂包含一种易裂解的键，可在多种温和条件下进行裂解，包括弱酸性条件。由于药物可以直接与连接剂结合，因此裂解可能导致原生药物的释放。该发明还提供了制备可裂解共轭物的方法。首选药物包括药物、毒素、生物反应修饰剂、放射诊断化合物、放射治疗化合物及其衍生物。本发明中使用的靶向分子可以是完整分子、其片段或其功能等效物。在特别优选的实施例中，靶向分子是针对人类肿瘤相关抗原的单克隆抗体。本发明还提供了将不带有靶向分子载体的药物输送到目标细胞的细胞质中的方法。向温血动物，如人类，给予可裂解共轭物的诊断/治疗有效剂量。该发明的另一个方面提供了分离化合物的方法。该化合物与已用上述连接剂衍生物修饰的固相共价结合，并通过多种温和条件以原生形式释放。该发明的另一个方面提供了使用与上述连接剂相关的试剂将自由巯基、氨基或羟基引入化合物的方法。该方法的首选用途是向蛋白质，如抗体或药物，添加自由氨基或自由巯基基团。
• Cleavable immunoconjugates for the delivery and release of agents in native form
  申请人：NEORX CORPORATION

  公开号：EP0318948A2

  公开（公告）日：1989-06-07

  The present invention provides a cleavable immunoconjugate whose linker contains a labile bond that is cleavable under a variety of mild conditions, including weakly acidic. Since the agent may be bonded directly to the linker, cleavage can result in release of native agent. The invention also provides methods for producing a cleavable immunoconjugate. Preferred agents include drugs, toxins, biological response modifiers, radiodiagnostic compounds, radiotherapeutic compounds, and derivatives thereof. The antibody employed in the invention may be an intact molecule, a fragment thereof, or a functional equivalent thereof. In a preferred embodiment, the specific antibody is a monoclonal antibody directed towards a tumor-associated antigen in man. The invention further provides a method for delivering to the cytoplasm of a target cell an agent free of its antibody carrier. A diagnostically or therapeutically effective dose of a cleavable immunoconjugate is administered to a mammal such as man. Another aspect of the invention provides a method for isolating a compound containing an available nucleophilic group, such as a free sulfhydryl, amino, or hydroxyl group. The compound binds covalently to a solid phase which has been derivatized with the linker described above and is released in native form by a variety of mild conditions. An additional aspect of the invention provides a method for introducing into a compound a free sulfhydryl, amine, or hydroxyl group by use of a reagent structurally related to the linker described above. Preferred uses of the method are to add a free amino or a free sulfhydryl group to a protein, such as an antibody. This method has broad application in the field of compound modification, especially protein modification.

  本发明提供了一种可裂解的免疫结合剂，其连接体含有可在包括弱酸性在内的各种温和条件下裂解的易变键。由于药剂可直接与连接体结合，因此裂解可导致原生药剂的释放。本发明还提供了生产可裂解免疫结合剂的方法。首选的药剂包括药物、毒素、生物反应调节剂、放射性诊断化合物、放射性治疗化合物及其衍生物。本发明中使用的抗体可以是完整的分子、其片段或其功能等同物。在一个优选的实施方案中，特异性抗体是针对人类肿瘤相关抗原的单克隆抗体。本发明进一步提供了一种向靶细胞的细胞质输送不含抗体载体的药剂的方法。将诊断或治疗有效剂量的可裂解免疫结合剂施用给哺乳动物，如人类。 本发明的另一方面提供了一种分离含有可用亲核基团（如游离巯基、氨基或羟基）的化合物的方法。该化合物与固相共价结合，固相已用上述连接剂衍生化，并在各种温和条件下以原生形式释放。 本发明的另一方面提供了一种方法，通过使用与上述连接剂结构相关的试剂，将游离的巯基、胺基或羟基引入化合物中。该方法的首选用途是向蛋白质（如抗体）中添加游离氨基或游离巯基。这种方法在化合物修饰领域，特别是蛋白质修饰领域有着广泛的应用。
• US4988496A
  申请人：——

  公开号：US4988496A

  公开（公告）日：1991-01-29