2,4-O-bis(trimethylsilyl)-5-fluorouracil | 66542-54-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯啉
• 英文名称: 2,4-O-bis(trimethylsilyl)-5-fluorouracil
• 英文别名: 5-fluorouracil；(5-Fluoro-2-trimethylsilyloxy-1,2,3,4-tetrahydropyrimidin-4-yl)oxy-trimethylsilane
• CAS: 66542-54-9
• 化学式: C₁₀H₂₃FN₂O₂Si₂
• 分子量: 278.474
• InChiKey: OBUWDWLIJPUVKF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  42.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-Fluorooxolan-2-ol 、 2,4-O-bis(trimethylsilyl)-5-fluorouracil 在 二甲基溴化硼 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 32.0h， 以22%的产率得到5-fluoro-1-(cis-3'-fluoro-2',3',4',5'-tetrahydro-2'-furanyl)uracil
  参考文献：
  名称：

  Synthesis of 1′,2′-cis-Nucleoside Analogues: Evidence of Stereoelectronic Control for S_N2 Reactions at the Anomeric Center of Furanosides

  摘要：

  We are reporting a highly diastereoselective route to 1 ',2 '-cis-nucleoside analogues in the D-ribo, D-lyxo, D-xylo, and D-arabinoside series. Five-membered ring lactols undergo highly selective N-glycosidation reactions in the presence of dimethylboron bromide with different silylated nucleobases. Stereoelectronic control plays a crucial role for the observed induction, and the products are proposed to be formed through S(N)2 "exploded" transition states. This approach shows great potential considering its simplicity and selectivity for the synthesis of nucleoside analogues, an important class of molecules in medicinal chemistry.

  DOI：

  10.1021/ja104429y
• 作为产物：
  描述：

  5-氟脲嘧啶 在 糖精 、 lithium hexamethyldisilazane 作用下， 以 乙腈 为溶剂， 反应 0.5h， 生成 2,4-O-bis(trimethylsilyl)-5-fluorouracil
  参考文献：
  名称：

  3′-Axial CH2OH Substitution on Glucopyranose does not Increase Glycogen Phosphorylase Inhibitory Potency. QM/MM-PBSA Calculations Suggest Why

  摘要：

  Glycogen phosphorylase is a molecular target for the design of potential hypoglycemic agents. Structure‐based design pinpointed that the 3′‐position of glucopyranose equipped with a suitable group has the potential to form interactions with enzyme’s cofactor, pyridoxal 5′‐phosphate (PLP), thus enhancing the inhibitory potency. Hence, we have investigated the binding of two ligands, 1‐(β‐d‐glucopyranosyl)5‐fluorouracil (GlcFU) and its 3′‐CH2OH glucopyranose derivative. Both ligands were found to be low micromolar inhibitors with Ki values of 7.9 and 27.1 μm, respectively. X‐ray crystallography revealed that the 3′‐CH2OH glucopyranose substituent is indeed involved in additional molecular interactions with the PLP γ‐phosphate compared with GlcFU. However, it is 3.4 times less potent. To elucidate this discovery, docking followed by postdocking Quantum Mechanics/Molecular Mechanics – Poisson–Boltzmann Surface Area (QM/MM‐PBSA) binding affinity calculations were performed. While the docking predictions failed to reflect the kinetic results, the QM/MM‐PBSA revealed that the desolvation energy cost for binding of the 3′‐CH2OH‐substituted glucopyranose derivative out‐weigh the enthalpy gains from the extra contacts formed. The benefits of performing postdocking calculations employing a more accurate solvation model and the QM/MM‐PBSA methodology in lead optimization are therefore highlighted, specifically when the role of a highly polar/charged binding interface is significant.

  DOI：

  10.1111/j.1747-0285.2012.01349.x

文献信息

• AFFINITY ILLUDOFULVENE CONJUGATES
  申请人：AF Chemicals, LLC,

  公开号：US20210155583A1

  公开（公告）日：2021-05-27

  In an embodiment of the invention, a composition for treating a cell population comprises a medicant. The medicant moiety can be an illudofulvene analog. In an embodiment of the invention, a composition for treating a cell population comprises an Affinity Medicant Conjugate (AMC). The affinity moiety can be an antibody, an antibody fragment, a receptor protein, a peptidic growth factor, an anti-angiogenic protein, a specific binding peptide, protease cleavable peptide, a glycopeptide, a peptide, a peptidic toxin, a protein toxin and an oligonucleotide. The affinity moiety can be covalently bound to the medicant via a linker.

  在该发明实施例中，用于治疗细胞群的组合物包括一种药物。该药物部分可以是伊卢多富烯类似物。在该发明实施例中，用于治疗细胞群的组合物包括亲和药物结合物（AMC）。亲和部分可以是抗体、抗体片段、受体蛋白、肽生长因子、抗血管生成蛋白、特异结合肽、蛋白酶可切割肽、糖肽、肽、肽毒素、蛋白毒素和寡核苷酸。亲和部分可以通过连接剂与药物共价结合。
• γ-Radiolysis of 1-Substituted 5-Fluorouracil Derivatives
  作者：Tokuyuki Kuroda、Koji Hisamura、Ikuo Matsukuma、Hiroshi Nishikawa、Nobuhiro Nakamizo

  DOI：10.1246/bcsj.62.674

  日期：1989.3

  A new concept, “Radiation-Induced Drug (RID)”, was proposed as a novel type of drugs for cancer therapy. To test the usefulness of this concept, 5-fluorouracil (5-FU) derivatives having various types of substituents at the 1-position were prepared and the γ-radiolyses of their aqueous solutions were studied. The compounds having sulfonyl and thioureido groups as the substituents produced efficiently 5-FU with high G values upon γ-irradiation. The medium effects on the radiolyses revealed that the above two substituents were removed mainly with HO· and hydrated electrons eeq−.

  提出了一种新的概念“辐射诱导药物（RID）”，作为癌症治疗的新型药物。为了测试这一概念的有效性，制备了不同取代基的5-氟尿嘧啶（5-FU）衍生物，并研究了其水溶液的γ辐射解离。具有磺酰基和硫脲基作为取代基的化合物在γ辐射下能有效地产生高G值的5-FU。对辐射解离的介质效应表明，上述两种取代基主要通过羟基自由基（HO·）和水合电子（eeq−）被去除。
• Novel β-L-1,3-thiazolidine pyrimidine nucleoside analogues: Design, synthesis, molecular docking, and anti-HIV activity
  作者：Shimoga Nagaraj Sriharsha、N．Habeela Jainab、Mahalakshmi Suresha Biradar、Shankar Thapa、E S Venkatesh、Durgesh Paresh Bidye、Gurubasavaraj Pujar、Sheshagiri Dixit

  DOI：10.1016/j.molstruc.2023.136304

  日期：2023.12

  and release. Moreover, their broad-spectrum antiviral activity and low cytotoxicity make them an attractive drug candidate for the treatment of viral infections. In this article, we detailed the synthesis of 1,3-thiazolidine pyrimidine derivatives substituted on the 5th position of the pyrimidine ring with different functional groups. The anti-HIV activity of the synthesized compounds was tested using

  1,3-噻唑烷嘧啶对多种病毒的显着活性使其成为一类可行的抗病毒药物。这些化合物表现出独特的作用机制，针对病毒生命周期的多个阶段，包括病毒进入、复制和释放。此外，它们的广谱抗病毒活性和低细胞毒性使它们成为治疗病毒感染的有吸引力的候选药物。在本文中，我们详细介绍了嘧啶环5位上被不同官能团取代的1,3-噻唑烷嘧啶衍生物的合成。使用 HIVRT 测定法测试了合成化合物的抗 HIV 活性。与 IC 50相比与标准奈韦拉平 (112.2 nM) 的值相比，用 Fluoro S4 (21.16 µM) 和 Bromo S5 (30.52 µM)取代的 1,3 噻唑烷嘧啶化合物仅具有中等抗 HIV 活性。类似地，化合物S5和S4对HIV-1逆转录酶的活性位点具有高亲和力，其对接分数分别为-89.5147和-82.5556 kcal/mol。