(S)-2-amino-N-(1-((2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)-3-methylbutanamide | 1018907-96-4

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: (S)-2-amino-N-(1-((2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)-3-methylbutanamide
• 英文别名: N-L-Valyl-2',2'-difluoro-2'-deoxycytidine；(2S)-2-amino-N-[1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-2-oxopyrimidin-4-yl]-3-methylbutanamide
• CAS: 1018907-96-4
• 化学式: C₁₄H₂₀F₂N₄O₅
• 分子量: 362.333
• InChiKey: JVILAFGBMQGADF-DLYFRVTGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  138
• 氢给体数：
  4
• 氢受体数：
  8

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  吉西他滨	Gemcitabine	95058-81-4	C9H11F2N3O4	263.201

反应信息

• 作为产物：
  描述：

  tert-butyl ((S)-1-((1-((2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)amino)-3-methyl-1-oxobutan-2-yl)carbamate 在 盐酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 以21 mg的产率得到(S)-2-amino-N-(1-((2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)-3-methylbutanamide
  参考文献：
  名称：

  吉西他滨-苏氨酸酰胺前药的合成对胰腺癌细胞具有有效的药代动力学特性。

  摘要：

  为了进一步研究基于氨基酸转运蛋白的前药抗癌策略，合成了几种氨基酸偶联的酰胺吉西他滨前药，以靶向胰腺癌细胞中的氨基酸转运蛋白。通过1 H-NMR和LC-MS证实了合成的氨基酸缀合的前药的结构。胰腺癌细胞AsPC1，BxPC-3，PANC-1和MIAPaCa-2似乎通过常规RT-PCR过表达了氨基酸转运蛋白LAT-1。在吉西他滨的六个氨基酸衍生物中，就抗癌作用而言，吉西他滨的苏氨酸衍生物（Gem-Thr）在胰腺癌细胞BxPC-3和MIAPaCa-2中比游离吉西他滨更有效。此外，Gem-Thr在PBS（pH 7.4），大鼠血浆和肝微粒体组分中代谢稳定。当将Gem-Thr以4 mg / kg的剂量静脉内给药于大鼠时，发现Gem-Thr可通过酰胺键裂解成功转化为吉西他滨。此外，与总的吉西他滨治疗相比，Gem-Thr显示形成的吉西他滨的全身暴露增加了1.83倍，这是由于总清除率明显降低（0.60对4.23

  DOI：

  10.3390/molecules23102608

文献信息

• Targeted therapeutics
  申请人：Madrigal Pharmaceuticals, Inc.

  公开号：US10376598B2

  公开（公告）日：2019-08-13

  The present invention provides pharmacological compounds including an effector moiety conjugated to a binding moiety that directs the effector moiety to a biological target of interest. Likewise, the present invention provides compositions, kits, and methods (e.g., therapeutic, diagnostic, and imaging) including the compounds. The compounds can be described as a protein interacting binding moiety-drug conjugate (SDC-TRAP) compounds, which include a protein interacting binding moiety and an effector moiety. For example, in certain embodiments directed to treating cancer, the SDC-TRAP can include an Hsp90 inhibitor conjugated to a cytotoxic agent as the effector moiety.

  本发明提供的药理化合物包括与结合基团共轭的效应分子，该结合基团可将效应分子导向感兴趣的生物靶标。同样，本发明还提供了包括这些化合物的组合物、试剂盒和方法（如治疗、诊断和成像）。这些化合物可被描述为蛋白质相互作用结合分子-药物共轭物（SDC-TRAP）化合物，其中包括蛋白质相互作用结合分子和效应分子。例如，在某些用于治疗癌症的实施方案中，SDC-TRAP 可包括与细胞毒剂共轭的 Hsp90 抑制剂作为效应分子。
• TARGETED THERAPEUTICS
  申请人：Synta Pharmaceuticals Corp.

  公开号：US20160375142A1

  公开（公告）日：2016-12-29

  The present invention provides pharmacological compounds including an effector moiety conjugated to a binding moiety that directs the effector moiety to a biological target of interest. Likewise, the present invention provides compositions, kits, and methods (e.g., therapeutic, diagnostic, and imaging) including the compounds. The compounds can be described as a protein interacting binding moiety-drug conjugate (SDC-TRAP) compounds, which include a protein interacting binding moiety and an effector moiety. For example, in certain embodiments directed to treating cancer, the SDC-TRAP can include an Hsp90 inhibitor conjugated to a cytotoxic agent as the effector moiety.
• [EN] TARGETED THERAPEUTICS<br/>[FR] THÉRAPIES CIBLÉES
  申请人：SYNTA PHARMACEUTICALS CORP

  公开号：WO2015066053A2

  公开（公告）日：2015-05-07

  The present invention provides pharmacological compounds including an effector moiety conjugated to a binding moiety that directs the effector moiety to a biological target of interest. Likewise, the present invention provides compositions, kits, and methods (e.g., therapeutic, diagnostic, and imaging) including the compounds. The compounds can be described as a protein interacting binding moiety-drug conjugate (SDC-TRAP) compounds, which include a protein interacting binding moiety and an effector moiety. For example, in certain embodiments directed to treating cancer, the SDC-TRAP can include an Hsp90 inhibitor conjugated to a cytotoxic agent as the effector moiety.
• Synthesis of Gemcitabine-Threonine Amide Prodrug Effective on Pancreatic Cancer Cells with Improved Pharmacokinetic Properties
  作者：Sungwoo Hong、Zhenghuan Fang、Hoi-Yun Jung、Jin-Ha Yoon、Soon-Sun Hong、Han-Joo Maeng

  DOI：10.3390/molecules23102608

  日期：——

  To investigate the amino acid transporter-based prodrug anticancer strategy further, several amino acid-conjugated amide gemcitabine prodrugs were synthesized to target amino acid transporters in pancreatic cancer cells. The structures of the synthesized amino acid-conjugated prodrugs were confirmed by ¹H-NMR and LC-MS. The pancreatic cancer cells, AsPC1, BxPC-3, PANC-1 and MIAPaCa-2, appeared to overexpress

  为了进一步研究基于氨基酸转运蛋白的前药抗癌策略，合成了几种氨基酸偶联的酰胺吉西他滨前药，以靶向胰腺癌细胞中的氨基酸转运蛋白。通过1 H-NMR和LC-MS证实了合成的氨基酸缀合的前药的结构。胰腺癌细胞AsPC1，BxPC-3，PANC-1和MIAPaCa-2似乎通过常规RT-PCR过表达了氨基酸转运蛋白LAT-1。在吉西他滨的六个氨基酸衍生物中，就抗癌作用而言，吉西他滨的苏氨酸衍生物（Gem-Thr）在胰腺癌细胞BxPC-3和MIAPaCa-2中比游离吉西他滨更有效。此外，Gem-Thr在PBS（pH 7.4），大鼠血浆和肝微粒体组分中代谢稳定。当将Gem-Thr以4 mg / kg的剂量静脉内给药于大鼠时，发现Gem-Thr可通过酰胺键裂解成功转化为吉西他滨。此外，与总的吉西他滨治疗相比，Gem-Thr显示形成的吉西他滨的全身暴露增加了1.83倍，这是由于总清除率明显降低（0.60对4.23