5-(苄氧基甲基)尿嘧啶 | 7295-02-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 5-(苄氧基甲基)尿嘧啶
• 英文名称: benzyl hydroxymethyl uridine
• 英文别名: 5-[(benzyloxy)methyl]uracil；5-Benzyloxymethyluracil；5-benzyloxymethyl-1H-pyrimidine-2,4-dione；1-benzyloxymethylpyrimidine-2,4-dione；5-(phenylmethoxymethyl)pyrimidine-2,4-diol
• CAS: 7295-02-5
• 化学式: C₁₂H₁₂N₂O₃
• mdl: MFCD00627705
• 分子量: 232.239
• InChiKey: QDNLNNAXVJQLJO-UHFFFAOYSA-N

物化性质

• 熔点：
  189-190 °C(Solv: 1,4-dioxane (123-91-1))
• 密度：
  1.239±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.166
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 危险品标志：
  Xi

反应信息

• 作为反应物：
  描述：

  5-(苄氧基甲基)尿嘧啶 在 4-二甲氨基吡啶 、 sodium hydroxide 、 N,O-双三甲硅基乙酰胺 、 偶氮二异丁腈 、 三氟甲磺酸三甲基硅酯 、 四丁基氟化铵 、 三正丁基氢锡 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 水 、 甲苯 、 乙腈 为溶剂， 反应 60.58h， 生成 5-(benzyloxy)methyl-2′-deoxyuridine
  参考文献：
  名称：

  Aromaticvs. Carbohydrate Residues in the Major Groove: Synthesis of 5-[(Benzyloxy)methyl]pyrimidine Nucleosides and Their Incorporation into Oligonucleotides

  摘要：

  The synthesis of 5-[(benzyloxy)methyl]-substituted pyrimidine 2'-deoxynucleosides 14 and 15 starting from the uracil derivative 6 and tetra-O-acetyl-D-ribose is described (Schemes 1-3). These nucleosides were converted to the corresponding cyanoethyl phosphoramidites 18 and 19, respectively, and incorporated into oligodeoxynucleotide decamers. The 5-[(benzyloxy)methyl]-nucleoside building blocks T-bo(d) and C-bom(d) (bo = benzyloxy, bom = (benzyloxy)methyl) - shape analogs of the naturally occurring glucosylated nucleosides 1 and 2 (see Fig. 1) - lead to weaker binding affinities of oligodeoxynucleotides pairing to DNA as well as RNA complements. The modification is more destabilizing in the case of T-bo(d) than C-bom(d). Analysis of the thermodynamics of duplex formation shows that T-bo(d) and C-bom(d), incorporation leads to a smaller entropy change in duplex formation that is, however, overcompensated by a less Favorable enthalpy term. Molecular-modeling studies suggest that the benzyl groups reside in the major groove which would explain the improved pairing entropy as a result of the exclusion of ordered H2O.

  DOI：

  10.1002/1522-2675(20000809)83:8<1962::aid-hlca1962>3.0.co;2-8
• 作为产物：
  描述：

  5-羟甲基脲嘧啶 、 苯甲醇 在 盐酸 作用下， 生成 5-(苄氧基甲基)尿嘧啶
  参考文献：
  名称：

  嘧啶 2,4-二酮在新型 HIV RT 抑制剂设计中的应用。

  摘要：

  嘧啶核是抗逆转录病毒药物开发中的多功能核心。在此基础上，合成了一系列与异恶唑烷核相连的嘧啶-2,4-二酮，并作为核苷类似物进行了测试，赋予了潜在的抗HIV（人类免疫缺陷病毒）活性。化合物 6a-c 的特征是在 C-3 处存在醚基，显示出纳摩尔范围内的 HIV 逆转录酶 (RT) 抑制剂活性以及低微摩尔范围内的 HIV 感染抑制剂活性，且无毒性。在相同的情况下，化合物 7b 仅显示出可忽略不计的 RT HIV 抑制作用。

  DOI：

  10.3390/molecules24091718

文献信息

• Sulfonamide derivatives
  申请人：Sankyo Company, Limited

  公开号：US06673804B1

  公开（公告）日：2004-01-06

  A compound of the formula (I) or a pharmacologically acceptable salt, ester or other derivative thereof: R1 is H or NHOH. R2 is H, optionally substituted alkyl, cycloalkyl or a group —AR6. A is an alkylene which may be optionally interrupted by O, —S(O)m— or —N(R9). R6 is a group (II), (III), (IV) X is O, S, —N(R10)—, —C(R11)(R12)—. Y is O, CO, —S(O)n—, —N(R10)—, —C(R11)(R12)—. Each of R7 and R8 is H, alkyl, COOH, optionally substituted alkyl, etc. Each of R9, R10, R11, and R12 is H, alkyl, etc. Each of m and n is 0 to 2. R3 is H, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl. R4 is optionally substituted (hetero)arylene. R5 is optionally substituted alkyl, optionally substituted (hetero)aryl. These compounds have matrixmetalloproteinase—13 inhibitory activity and aglycanase inhibitory activity.

  公式（I）的化合物或其药理学上可接受的盐、酯或其他衍生物： R1为H或NHOH。R2为H，可选择地取代的烷基，环烷基或一种—AR6基团。 A为一种可以选择地被O、—S(O)m—或—N(R9)中断的烷基。R6为一种（II）、（III）、（IV）基团。 X为O、S、—N(R10)—、—C(R11)(R12)—。Y为O、CO、—S(O)n—、—N(R10)—、—C(R11)(R12)—。R7和R8中的每一个为H、烷基、COOH、可选择地取代的烷基等。R9、R10、R11和R12中的每一个为H、烷基等。m和n中的每一个为0到2。R3为H、可选择地取代的烷基、可选择地取代的环烷基、可选择地取代的烯基、可选择地取代的炔基。R4为可选择地取代的（杂）芳基。R5为可选择地取代的烷基、可选择地取代的（杂）芳基。这些化合物具有基质金属蛋白酶-13抑制活性和糖基酶抑制活性。
• [EN] NUCLEOTIDE AND NUCLEOSIDE THERAPEUTIC COMPOSITIONS AND USES RELATED THERETO<br/>[FR] COMPOSITIONS THÉRAPEUTIQUES RENFERMANT DES NUCLÉOTIDES ET DES NUCLÉOSIDES ET UTILISATIONS ASSOCIÉES
  申请人：UNIV EMORY

  公开号：WO2014124430A1

  公开（公告）日：2014-08-14

  This disclosure relates to nucleotide and nucleoside therapeutic compositions and uses related thereto. In certain embodiments, the disclosure relates to halogenated nucleosides optionally conjugated to a phosphorus oxide or pharmaceutically acceptable salts thereof. In certain embodiments, the disclosure relates to conjugate compounds or pharmaceutically acceptable salts thereof comprising an amino acid ester or a sphingolipid or derivative linked by a phosphorus oxide to a nucleotide or nucleoside. In certain embodiments, the disclosure contemplates pharmaceutical compositions comprising these compounds for uses in treating infectious diseases, viral infections, and cancer.

  这项披露涉及核苷酸和核苷类治疗组合物及其相关用途。在某些实施例中，该披露涉及卤代核苷，可选择地与磷氧化物或其药用可接受盐结合。在某些实施例中，该披露涉及结合物或其药用可接受盐，包括通过磷氧化物与核苷酸或核苷相连的氨基酸酯或鞘脂类或衍生物。在某些实施例中，该披露考虑了包括这些化合物的药用组合物，用于治疗传染病、病毒感染和癌症。
• Copper-catalyzed Synthesis and Antimicrobial Activity of Disubstituted 1,2,3-Triazoles Starting from 1-Propargyluracils and Ethyl (4-Azido- 1,2,3-trihydroxybutyl)furan-3-carboxylate
  作者：Wael A. El-Sayed、Adel A.-H. Abdel-Rahman

  DOI：10.1515/znb-2010-0110

  日期：2010.1.1

  1,3-Dipolar cycloaddition reactions of 1-propargyluracils 2a - h with the azido derivative 3 afforded the corresponding 1,2,3-triazoles 4a - h. Hydrazinolysis of the esters 4a - h gave the corresponding acid hydrazides 5a - h. Reaction of 5a - h with carbon disulfide in ethanol afforded 6a - h. The antimicrobial activity of compounds 4 - 6 was determined

  1,3-双极环加成反应将1-丙炔基尿嘧啶2a - h与偶氮衍生物3反应，得到相应的1,2,3-三唑4a - h。酯类化合物4a - h的肼解反应得到相应的酸肼5a - h。将5a - h与乙醇中的二硫化碳反应得到6a - h。测定了化合物4-6的抗菌活性。
• Nucleobase dendrimer as a multidentate ligand for a rare-earth metal ion
  作者：Masahide Tominaga、Jun Hosogi、Katsuaki Konishi、Takuzo Aida

  DOI：10.1039/b000318m

  日期：——

  Novel dendritic macromolecules consisting of uracil units (LnU-OBn) with the numbers of the nucleobase layers (n) of 2–4 were synthesized; L3U-OBn and L4U-OBn both formed 1∶1 complexes with La3+, where the L4U-OBn–La3+ complex, in particular, was highly robust towards methanolysis.

  合成了由尿嘧啶单元（LnU-OBn）组成的新型树枝状大分子，核碱基层数（n）为 2-4 层；L3U-OBn 和 L4U-OBn 均与 La3+ 形成 1∶1 复合物，其中 L4U-OBn-La3+ 复合物对甲醇分解具有很强的稳定性。
• Modification of N-hydroxycytidine yields a novel lead compound exhibiting activity against the Venezuelan equine encephalitis virus
  作者：Isaac L. Downs、A. David Ordonez Luna、Krishna P. Kota、Sarah K. Rubin、Serena S. Shirsekar、Michael D. Ward、Rekha G. Panchal、Vladislav A. Litosh

  DOI：10.1016/j.bmcl.2023.129432

  日期：2023.10

  antiviral compounds with diminished side effects. This presumption is due to the substantial structural difference with natural cytidine leading to less recognizability by host cell enzymes. Among the 42 antimetabolite species that have been synthesized and screened against VEEV, one hit compound was identified. The structural features of the modifying moiety were similar to those of the anticancer lead

  能够干扰核酸合成的核苷和核碱基类似物在对抗传染病方面发挥了重要作用。然而，这些药物中的许多都与重要且可能致命的脱靶细胞内效应有关，从而限制了它们的使用。基于之前发现的碱基修饰的 2'-脱氧尿苷，与抗代谢化疗药物相比，它表现出高抗癌活性，同时对快速分裂的正常人类细胞表现出较低的毒性，我们假设N 4 -羟基胞苷 (NHC) 分子的类似修饰将提供副作用减少的新型抗病毒化合物。这一推测是由于与天然胞苷的显着结构差异导致宿主细胞酶的识别能力较低。在针对 VEEV 合成和筛选的 42 种抗代谢药物中，鉴定出一种有效化合物。该修饰部分的结构特征与之前报道的抗癌先导2′-脱氧尿苷衍生物的结构特征相似，为进一步进行针对先导改进的构效关系（SAR）研究提供了机会，并深入了解作用机制，这可以导致识别针对广谱 RNA 病毒感染的候选药物。