benzyl (2S)-1-[(2R)-2-aminopropanoyl]pyrrolidine-2-carboxylate | 120979-63-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: benzyl (2S)-1-[(2R)-2-aminopropanoyl]pyrrolidine-2-carboxylate
• CAS: 120979-63-7
• 化学式: C₁₅H₂₀N₂O₃
• 分子量: 276.335
• InChiKey: DIQUVKBEJJCUCP-YPMHNXCESA-N

物化性质

• 沸点：
  437.5±45.0 °C(Predicted)
• 密度：
  1.201±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  72.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  benzyl (2S)-1-[(2R)-2-aminopropanoyl]pyrrolidine-2-carboxylate 在 盐酸 、 1-羟基苯并三唑 、 苯甲醚 、 N,N'-二环己基碳二亚胺 作用下， 以 1,4-二氧六环 、 氯仿 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  Studies of a Peptide Antibiotic “Gratisin”. II

  摘要：

  为了研究 "gratisin "相关多肽环(-Val-Orn-Leu-d-Phe-Pro-d-Tyr-)2（GR-I）的结构-活性关系，合成了其两个类似物环(-Val-Orn-Leu-d-Ala-Pro-d-Tyr-)2 (6a)和环(-Val-Orn-Leu-d-Phe-Pro-d-Ala-)2 (6b)。这些合成肽在水溶液中的 CD 光谱与 GR-I 相似，表明这些肽在水溶液中具有相似的构象。6b 的活性是 GR-I 的一半，而 6a 则没有显示出任何抗生素活性。这些结果表明，Pro残基之前的d-Phe残基的苯基是显示活性的必要条件，而Pro残基之后的d-Tyr残基的对羟基苯基则不是必要条件。

  DOI：

  10.1246/bcsj.60.2101
• 作为产物：
  描述：

  N-Boc-D-Ala-L-Pro-OBzl 在 盐酸 、 苯甲醚 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.5h， 生成 benzyl (2S)-1-[(2R)-2-aminopropanoyl]pyrrolidine-2-carboxylate
  参考文献：
  名称：

  Studies of a Peptide Antibiotic “Gratisin”. II

  摘要：

  为了研究 "gratisin "相关多肽环(-Val-Orn-Leu-d-Phe-Pro-d-Tyr-)2（GR-I）的结构-活性关系，合成了其两个类似物环(-Val-Orn-Leu-d-Ala-Pro-d-Tyr-)2 (6a)和环(-Val-Orn-Leu-d-Phe-Pro-d-Ala-)2 (6b)。这些合成肽在水溶液中的 CD 光谱与 GR-I 相似，表明这些肽在水溶液中具有相似的构象。6b 的活性是 GR-I 的一半，而 6a 则没有显示出任何抗生素活性。这些结果表明，Pro残基之前的d-Phe残基的苯基是显示活性的必要条件，而Pro残基之后的d-Tyr残基的对羟基苯基则不是必要条件。

  DOI：

  10.1246/bcsj.60.2101

文献信息

• [EN] FAP-ACTIVATED THERAPEUTIC AGENTS, AND USES RELATED THERETO<br/>[FR] AGENTS THÉRAPEUTIQUES ACTIVÉS PAR FAP, ET UTILISATIONS ASSOCIÉES
  申请人：TUFTS COLLEGE

  公开号：WO2015192123A1

  公开（公告）日：2015-12-17

  Disclosed are prodrugs of cytotoxic anthracyclines (such as doxorubicin) and other therapeutic agents that are selectively cleaved and activated by fibroblast activating protein (FAP). The prodrugs are useful for targeted delivery of cytotoxic and other agents to FAP- expressing tissues, including cancer (e.g., solid tumors). Also provided are pharmaceutical compounds comprising the prodrugs, as well as methods of using the prodrugs to treat a disorder characterized by FAP upregulation, e.g., cancer, fibrosis, and inflammation.

  本文披露了细胞毒性蒽环类似物（如阿霉素）和其他治疗剂的前药，这些前药通过成纤维细胞激活蛋白（FAP）选择性地被切割和激活。这些前药可用于将细胞毒性和其他药物靶向输送至表达FAP的组织，包括癌症（如实体肿瘤）。还提供了包含这些前药的药物化合物，以及使用这些前药治疗由FAP上调引起的疾病的方法，例如癌症、纤维化和炎症。
• FAP-activated therapeutic agents, and uses related thereto
  申请人：TRUSTEES OF TUFTS COLLEGE

  公开号：US10245248B2

  公开（公告）日：2019-04-02

  Disclosed are prodrugs of therapeutic or imaging agents, which prodrugs are selectively cleaved by fibroblast activating protein (FAP) to release the agents. Upon cleavage by FAP of the FAP substrate, the prodrug releases the agent in its active form or in a form that is readily metabolized to its active form. Pharmaceutical compositions comprising the prodrugs, as well as methods of using the prodrugs to treat a disorder characterized by FAP upregulation are also disclosed.

  所公开的是治疗剂或成像剂的原药，这些原药可被成纤维细胞活化蛋白（FAP）选择性地裂解以释放药剂。在 FAP 对 FAP 底物进行裂解时，原药以其活性形式或易于代谢为其活性形式的形式释放药剂。此外，还公开了包含原药的药物组合物，以及使用原药治疗以 FAP 上调为特征的疾病的方法。
• Fap-activated therapeutic agents, and uses related thereto
  申请人：BACH BIOSCIENCES, LLC

  公开号：US11033525B2

  公开（公告）日：2021-06-15

  Disclosed are prodrugs of cytotoxic anthracyclines (such as doxorubicin) and other therapeutic agents that are selectively cleaved and activated by fibroblast activating protein (FAP). The prodrugs are useful for targeted delivery of cytotoxic and other agents to FAP-expressing tissues, including cancer (e.g., solid tumors). Also provided are pharmaceutical compounds comprising the prodrugs, as well as methods of using the prodrugs to treat a disorder characterized by FAP upregulation, e.g., cancer, fibrosis, and inflammation.

  所公开的是细胞毒性蒽环类（如多柔比星）和其他治疗剂的原药，它们可被成纤维细胞活化蛋白（FAP）选择性地裂解和激活。这些原药可用于向表达 FAP 的组织（包括癌症（如实体瘤））靶向输送细胞毒性药物和其他药物。此外，还提供了包含这些原药的药物化合物，以及使用这些原药治疗以 FAP 上调为特征的疾病（如癌症、纤维化和炎症）的方法。
• FAP-ACTIVATED THERAPEUTIC AGENTS, AND USES RELATED THERETO
  申请人：TRUSTEES OF TUFTS COLLEGE

  公开号：US20170119901A1

  公开（公告）日：2017-05-04

  Disclosed are prodrugs of therapeutic or imaging agents, which prodrugs are selectively cleaved by fibroblast activating protein (FAP) to release the agents. Upon cleavage by FAP of the FAP substrate, the prodrug releases the agent in its active form or in a form that is readily metabolized to its active form. Pharmaceutical compositions comprising the prodrugs, as well as methods of using the prodrugs to treat a disorder characterized by FAP upregulation are also disclosed.
• FAP-Activated Therapeutic Agents, and Uses Related Thereto
  申请人：TRUSTEES OF TUFTS COLLEGE

  公开号：US20170128476A1

  公开（公告）日：2017-05-11

  Disclosed are prodrugs of anthracyclines (such as doxorubicin) and derivatives thereof that are selectively cleaved and activated by fibroblast activating protein (FAP). The prodrugs are useful for targeted delivery of “warhead” anthracycline or anthracycline derivative to FAP-expressing tissues, including cancer (e.g., solid tumors). Also provided are pharmaceutical compositions comprising the prodrugs, as well as methods of using the prodrugs to treat a disorder characterized by FAP upregulation, e.g., cancer, undesirable fibrosis, and undesirable inflammation.