4-(propargyloxycarbonylamino)-1-(2-deoxy-2,2-difluoro-β-D-erythro-pentofuranosyl)pyrimidin-2(1H)-one | 1613293-14-3

• 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-(propargyloxycarbonylamino)-1-(2-deoxy-2,2-difluoro-β-D-erythro-pentofuranosyl)pyrimidin-2(1H)-one
• 英文别名: 4-N-(propargyloxycarbonyl)-2'-deoxy-2',2'-difluorocytidine；propargyl-(4-N-gemcitabine)carbamate；4-N-propargyloxycarbonylgemcitabine；prop-2-ynyl N-[1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-2-oxopyrimidin-4-yl]carbamate
• CAS: 1613293-14-3
• 化学式: C₁₃H₁₃F₂N₃O₆
• 分子量: 345.26
• InChiKey: CKHLNVKYMDDQBG-SZEHBUNVSA-N

物化性质

• 密度：
  1.58±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  121
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-(propargyloxycarbonylamino)-1-(2-deoxy-2,2-difluoro-β-D-erythro-pentofuranosyl)pyrimidin-2(1H)-one 在 copper(ll) sulfate pentahydrate 、 sodium ascorbate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 24.0h， 生成 吉西他滨
  参考文献：
  名称：

  含有甲基三唑或酯-甲基三唑接头的新型吉西他滨-核苷类似物二聚体的合成及体外抗癌活性。

  摘要：

  使用“点击”化学方法合成了两个系列的新型吉西他滨-核苷类似物二聚体。在第一系列二聚体（的21 - 30），该核苷单位用一个稳定的连接methyltriazole 4 Ñ -3'（或5'）ç接头，而第二系列（31 - 40）配有一个可裂解的酯，methyltriazole 4 N -3'（或5'）C接头。Dimers 21 – 40使用磺基罗丹明，对五种人类癌细胞系（例如宫颈癌（HeLa），鼻咽癌（KB），肺脏（A549），脑（U87），肝脏（HepG2）和正常皮肤成纤维细胞系（HDF）的细胞毒性活性进行了评估。 B（SRB）分析。化合物29包括两个吉西他滨（DFDC）单元表现出最高的活性二聚体中21 - 30。在所有研究的癌细胞系中，化合物29的活性均高于dFdC。观察到的化合物活性的类似的命令25，28，和30。化合物39显示出合成的所有二聚体中最好的活性，包括两个具有可裂解接头的吉西他

  DOI：

  10.1016/j.bmcl.2019.08.003
• 作为产物：
  描述：

  盐酸吉西他滨 在 吡啶 、 咪唑 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 4-(propargyloxycarbonylamino)-1-(2-deoxy-2,2-difluoro-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

• [EN] CYTIDINE DERIVATIVES AND METHODS OF FORMING CYTIDINE DERIVATIVES<br/>[FR] DÉRIVÉS DE CYTIDINE ET PROCÉDÉS DE FORMATION DE DÉRIVÉS DE CYTIDINE
  申请人：AENORASIS COMMERCIAL COMPANY OF PHARMACEUTICAL AND MEDICAL PRODUCTS AND MACHINES SA

  公开号：WO2020216646A1

  公开（公告）日：2020-10-29

  Disclosed herein are nucleoside derivatives, cytidine derivatives and Gemcitabine derivatives and methods of forming nucleoside derivatives, cytidine derivatives and Gemcitabine derivatives.

  本文披露了核苷衍生物、胞苷衍生物和吉西他滨衍生物以及形成核苷衍生物、胞苷衍生物和吉西他滨衍生物的方法。
• Synthesis and in vitro anticancer activity of new gemcitabine-nucleoside analogue dimers containing methyltriazole or ester-methyltriazole linker
  作者：Roksana Trznadel、Aleksandra Singh、Natalia Kleczewska、Joanna Liberska、Piotr Ruszkowski、Lech Celewicz

  DOI：10.1016/j.bmcl.2019.08.003

  日期：2019.9

  units exhibited the highest activity among dimers 21–30. The activity of compound 29 was higher than that of dFdC in all the studied cancer cell lines. A similar order of activity was observed for compounds 25, 28, and 30. The best activity among all the dimers synthesized was displayed by compound 39, comprising two gemcitabine units with a cleavable linker. The activity of compound 39 was 5 to 9 times

  使用“点击”化学方法合成了两个系列的新型吉西他滨-核苷类似物二聚体。在第一系列二聚体（的21 - 30），该核苷单位用一个稳定的连接methyltriazole 4 Ñ -3'（或5'）ç接头，而第二系列（31 - 40）配有一个可裂解的酯，methyltriazole 4 N -3'（或5'）C接头。Dimers 21 – 40使用磺基罗丹明，对五种人类癌细胞系（例如宫颈癌（HeLa），鼻咽癌（KB），肺脏（A549），脑（U87），肝脏（HepG2）和正常皮肤成纤维细胞系（HDF）的细胞毒性活性进行了评估。 B（SRB）分析。化合物29包括两个吉西他滨（DFDC）单元表现出最高的活性二聚体中21 - 30。在所有研究的癌细胞系中，化合物29的活性均高于dFdC。观察到的化合物活性的类似的命令25，28，和30。化合物39显示出合成的所有二聚体中最好的活性，包括两个具有可裂解接头的吉西他
• 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.