4-allyloxycarbonylamino-1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydropyrimidin-2-one | 688008-78-8

• 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-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydropyrimidin-2-one
• 英文别名: 4-(allyloxycarbonylamino)-1-(2-deoxy-2,2-difluoro-β-D-erythropentofuranosyl)pyrimidin-2(1H)-one；2'-deoxy-2',2'-difluoro-D-ribofuranosyl-N⁴-(allyloxycarbonyl)cytosine；prop-2-enyl N-[1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-2-oxopyrimidin-4-yl]carbamate
• CAS: 688008-78-8
• 化学式: C₁₃H₁₅F₂N₃O₆
• 分子量: 347.275
• InChiKey: WXUDDKMWTLXNBA-SZEHBUNVSA-N

物化性质

• 密度：
  1.59±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  24
• 可旋转键数：
  6
• 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-allyloxycarbonylamino-1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydropyrimidin-2-one 在 [CpRu(8-hydroxyquinoline)(η³-allyl)]PF₆ 作用下， 反应 8.0h， 以94.31%的产率得到吉西他滨
  参考文献：
  名称：

  用于 HER2 靶向化疗的 Affibody-钌催化剂混合物的原位前药活化

  摘要：

  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。

  DOI：

  10.1002/anie.202202855
• 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 21.0h， 生成 4-allyloxycarbonylamino-1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydropyrimidin-2-one
  参考文献：
  名称：

  一种抗体偶联剂及其制备方法与应用

  摘要：

  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。

  公开号：

  CN114957346B

文献信息

• GEMCITABINE PRODRUGS AND USES THEREOF
  申请人：BoYen Therapeutics, Inc.

  公开号：US20140134160A1

  公开（公告）日：2014-05-15

  The present invention provides compounds according to formula I: and pharmaceutically acceptable salts thereof. For compounds of formula I, R 1 and R 2 are independently selected from the group consisting of H, —C(═O)—(CH 2 ) 2 -aryl, and —C(═O)—(CH 2 ) n —C(═O)—NH-aryl. The subscript n is from 2 to 6. R 3 is selected from the group consisting of H and —C(═O)—O—R 4 ; and R 4 is selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, arylalkyl, substituted arylalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, heteroalkyl and substituted heteroalkyl. Compounds are provided wherein at least one of R 1 and R 2 is other than H. Pharmaceutical compositions, methods for inhibiting the growth of cancer cells, and methods for the treatment of cancer are also provided.

  本发明提供了公式I的化合物及其药学上可接受的盐。对于公式I的化合物，R1和R2独立地选择自H，—C（═O）—（CH2）2-芳基和—C（═O）—（CH2）n—C（═O）—NH-芳基的群组。下标n为2至6。R3选择自H和—C（═O）—O—R4的群组；而R4选择自烷基，取代烷基，烯基，取代烯基，炔基，取代炔基，芳基烷基，取代芳基烷基，环杂芳基烷基，取代环杂芳基烷基，杂基和取代杂基的群组。提供了至少一个R1和R2不是H的化合物。还提供了制药组合物，抑制癌细胞生长的方法和治疗癌症的方法。
• Gemcitabine prodrugs and uses thereof
  申请人：BoYen Therapeutics, Inc.

  公开号：US08956613B2

  公开（公告）日：2015-02-17

  The present invention provides compounds according to formula I: and pharmaceutically acceptable salts thereof. For compounds of formula I, R1 and R2 are independently selected from the group consisting of H, —C(═O)—(CH2)2-aryl, and —C(═O)—(CH2)n—C(═O)—NH-aryl. The subscript n is from 2 to 6. R3 is selected from the group consisting of H and —C(═O)—O—R4; and R4 is selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, arylalkyl, substituted arylalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, heteroalkyl and substituted heteroalkyl. Compounds are provided wherein at least one of R1 and R2 is other than H. Pharmaceutical compositions, methods for inhibiting the growth of cancer cells, and methods for the treatment of cancer are also provided.

  本发明提供了公式I的化合物及其药学上可接受的盐。对于公式I的化合物，R1和R2分别选自H，—C(═O)—(CH2)2-芳基和—C(═O)—(CH2)n—C(═O)—NH-芳基。下标n为2至6。R3选自H和—C(═O)—O—R4；R4选自烷基，取代烷基，烯基，取代烯基，炔基，取代炔基，芳基烷基，取代芳基烷基，环杂芳基烷基，取代环杂芳基烷基，杂基和取代杂基。提供了至少其中之一的R1和R2不是H的化合物。还提供了药物组合物、抑制癌细胞生长的方法以及治疗癌症的方法。
• 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.
• Synthesis and Biological Activity of a Gemcitabine Phosphoramidate Prodrug
  作者：Weidong Wu、Jennifer Sigmond、Godefridus J. Peters、Richard F. Borch

  DOI：10.1021/jm070269u

  日期：2007.7.1

  A gemcitabine (2',2'-difluorodeoxycytidine, dFdC) phosphoramidate prodrug designed for the intracellular delivery of gemcitabine 5'-monophosphate was synthesized. The prodrug was about an order of magnitude less active than gemcitabine against wild-type cells, and the nucleoside transport inhibitor dipyridamole reduced prodrug activity. The prodrug was more active than gemcitabine against two deoxycytidine kinase-deficient cell lines. The results suggest that the prodrug is a potent growth inhibitor that can bypass dCK deficiency at higher drug concentrations.
• Gemcitabine Prodrugs, Pharmaceutical Compositions and Uses Thereof
  申请人：Gallop A. Mark

  公开号：US20080021208A1

  公开（公告）日：2008-01-24

  The present invention provides gemcitabine prodrugs, methods of making gemcitabine prodrugs, pharmaceutical compositions of gemcitabine prodrugs and methods of using gemcitabine prodrugs and pharmaceutical compositions of using gemcitabine prodrugs to treat or prevent diseases or disorders such as cancer or viral infections.