4-(allyloxycarbonylamino)-1-(2-deoxy-2,2-difluoro-5-O-[tertbutyl(dimethyl)silyl]-β-D-erythro-pentofuranosyl)pyrimidin-2(1H)-one | 688008-95-9

• 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: 4-(allyloxycarbonylamino)-1-(2-deoxy-2,2-difluoro-5-O-[tertbutyl(dimethyl)silyl]-β-D-erythro-pentofuranosyl)pyrimidin-2(1H)-one
• 英文别名: prop-2-enyl N-[1-[(2R,4R,5R)-5-[[tert-butyl(dimethyl)silyl]oxymethyl]-3,3-difluoro-4-hydroxyoxolan-2-yl]-2-oxopyrimidin-4-yl]carbamate
• CAS: 688008-95-9
• 化学式: C₁₉H₂₉F₂N₃O₆Si
• 分子量: 461.538
• InChiKey: ZIGFVCANFHASBX-BPLDGKMQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.89
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  110
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-(allyloxycarbonylamino)-1-(2-deoxy-2,2-difluoro-5-O-[tertbutyl(dimethyl)silyl]-β-D-erythro-pentofuranosyl)pyrimidin-2(1H)-one 在 四丁基氟化铵 作用下， 以 四氢呋喃 、 aq. phosphate buffer 为溶剂， 生成 吉西他滨
  参考文献：
  名称：

  Development and Bioorthogonal Activation of Palladium-Labile Prodrugs of Gemcitabine

  摘要：

  Bioorthogonal chemistry has become one of the main driving forces in current chemical biology, inspiring the search for novel biocompatible chemospecific reactions for the past decade. Alongside the well-established labeling strategies that originated the bioorthogonal paradigm, we have recently proposed the use of heterogeneous palladium chemistry and bioorthogonal Pd(0)-labile prodrugs to develop spatially targeted therapies. Herein, we report the generation of biologically inert precursors of cytotoxic gemcitabine by introducing Pd(0)-cleavable groups in positions that are mechanistically relevant for gemcitabine's pharmacological activity. Cell viability studies in pancreatic cancer cells showed that carbamate functionalization of the 4-amino group of gemcitabine significantly reduced (>23-fold) the prodrugs' cytotoxicity. The N-propargyloxycarbonyl (N-Poc) promoiety displayed the highest sensitivity to heterogeneous palladium catalysis under biocompatible conditions, with a reaction half-life of less than 6 h. Zebrafish studies with allyl, propargyl, and benzyl carbamate-protected rhodamines confirmed N-Poc as the most suitable masking group for implementing in vivo bioorthogonal organometallic chemistry.

  DOI：

  10.1021/jm500531z
• 作为产物：
  描述：

  盐酸吉西他滨 在 吡啶 、 咪唑 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 4-(allyloxycarbonylamino)-1-(2-deoxy-2,2-difluoro-5-O-[tertbutyl(dimethyl)silyl]-β-D-erythro-pentofuranosyl)pyrimidin-2(1H)-one
  参考文献：
  名称：

  Development and Bioorthogonal Activation of Palladium-Labile Prodrugs of Gemcitabine

  摘要：

  Bioorthogonal chemistry has become one of the main driving forces in current chemical biology, inspiring the search for novel biocompatible chemospecific reactions for the past decade. Alongside the well-established labeling strategies that originated the bioorthogonal paradigm, we have recently proposed the use of heterogeneous palladium chemistry and bioorthogonal Pd(0)-labile prodrugs to develop spatially targeted therapies. Herein, we report the generation of biologically inert precursors of cytotoxic gemcitabine by introducing Pd(0)-cleavable groups in positions that are mechanistically relevant for gemcitabine's pharmacological activity. Cell viability studies in pancreatic cancer cells showed that carbamate functionalization of the 4-amino group of gemcitabine significantly reduced (>23-fold) the prodrugs' cytotoxicity. The N-propargyloxycarbonyl (N-Poc) promoiety displayed the highest sensitivity to heterogeneous palladium catalysis under biocompatible conditions, with a reaction half-life of less than 6 h. Zebrafish studies with allyl, propargyl, and benzyl carbamate-protected rhodamines confirmed N-Poc as the most suitable masking group for implementing in vivo bioorthogonal organometallic chemistry.

  DOI：

  10.1021/jm500531z

文献信息

• In Situ Prodrug Activation by an Affibody‐Ruthenium Catalyst Hybrid for HER2‐Targeted Chemotherapy
  作者：Zhennan Zhao、Xuan Tao、Yanxuan Xie、Qi Lai、Wenkai Lin、Kai Lu、Jinhui Wang、Wei Xia、Zong‐Wan Mao

  DOI：10.1002/anie.202202855

  日期：2022.6.27

  An affibody-ruthenium catalyst hybrid (Ru-HER2) binds to the HER2 receptor on cancer cells and catalyzes the in situ activation of gemcitabine prodrug, resulting in enhanced anticancer activity via the synergism between the HER2 signaling pathway blockade and gemcitabine-induced DNA damage. Therefore, the catalytic chemotherapy selectively inhibits the growth of HER2-positive cancer cells and significantly

  一种亲和体-钌催化剂杂化物 ( Ru-HER2 ) 与癌细胞上的 HER2 受体结合并催化吉西他滨前药的原位活化，从而通过 HER2 信号通路阻断和吉西他滨诱导的 DNA 损伤之间的协同作用增强抗癌活性。因此，催化化疗选择性地抑制HER2阳性癌细胞的生长，显着降低对正常细胞的副作用。
• 一种抗体偶联剂及其制备方法与应用
  申请人：中山大学

  公开号：CN114957346B

  公开（公告）日：2023-08-25

  本发明属于生物医药技术领域，具体涉及一种抗体偶联剂及其制备方法与应用。本发明制备得到的抗体偶联剂RMI能利用点击反应偶联在特异性识别HER2或PD‑L1的抗体片段C端的半胱氨酸巯基上，得到抗体偶联催化剂，抗体偶联催化剂与小分子前药联合使用后，小分子前药在抗体偶联催化剂的催化下在肿瘤细胞内断键生成小分子药物，达到靶向治疗肿瘤的作用，降低小分子药物对非靶细胞的毒副作用，抗体偶联催化剂还能结合肿瘤细胞膜受体抑制相关的信号通路，实现联合治疗的效果。
• Development and Bioorthogonal Activation of Palladium-Labile Prodrugs of Gemcitabine
  作者：Jason T. Weiss、John C. Dawson、Craig Fraser、Witold Rybski、Carmen Torres-Sánchez、Mark Bradley、E. Elizabeth Patton、Neil O. Carragher、Asier Unciti-Broceta

  DOI：10.1021/jm500531z

  日期：2014.6.26

  Bioorthogonal chemistry has become one of the main driving forces in current chemical biology, inspiring the search for novel biocompatible chemospecific reactions for the past decade. Alongside the well-established labeling strategies that originated the bioorthogonal paradigm, we have recently proposed the use of heterogeneous palladium chemistry and bioorthogonal Pd(0)-labile prodrugs to develop spatially targeted therapies. Herein, we report the generation of biologically inert precursors of cytotoxic gemcitabine by introducing Pd(0)-cleavable groups in positions that are mechanistically relevant for gemcitabine's pharmacological activity. Cell viability studies in pancreatic cancer cells showed that carbamate functionalization of the 4-amino group of gemcitabine significantly reduced (>23-fold) the prodrugs' cytotoxicity. The N-propargyloxycarbonyl (N-Poc) promoiety displayed the highest sensitivity to heterogeneous palladium catalysis under biocompatible conditions, with a reaction half-life of less than 6 h. Zebrafish studies with allyl, propargyl, and benzyl carbamate-protected rhodamines confirmed N-Poc as the most suitable masking group for implementing in vivo bioorthogonal organometallic chemistry.