6-(3-benzyloxy-2-hydroxypropyl)-2,4-dimethoxy-5-methylpyrimidine | 856766-74-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 6-(3-benzyloxy-2-hydroxypropyl)-2,4-dimethoxy-5-methylpyrimidine
• 英文别名: 6-(3-benzyloxy-2-hydroxypropyl)-5-methyl-2,4-dimethoxypyrimidine；1-(2,6-Dimethoxy-5-methylpyrimidin-4-yl)-3-phenylmethoxypropan-2-ol
• CAS: 856766-74-0
• 化学式: C₁₇H₂₂N₂O₄
• 分子量: 318.373
• InChiKey: JUCFRVYVPYKINA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  23
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  73.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-(3-benzyloxy-2-hydroxypropyl)-2,4-dimethoxy-5-methylpyrimidine 在 水 、 三氯化硼 、 碳酸氢钠 、 乙酰氯 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 10.0h， 生成 6-(2,3-二羟基丙基)-5-甲基-2,4(1H,3H)-嘧啶二酮
  参考文献：
  名称：

  Synthesis, ¹⁸F‐Radiolabelling and Biological Evaluations of C‐6 Alkylated Pyrimidine Nucleoside Analogues

  摘要：

  Synthesis of pyrimidine derivatives with a side-chain attached to the C-6 of pyrimidine ring (6-14) is reported. Target compounds 8 and 12 were subjected to in vitro phosphorylation tests, determination of their binding affinities to herpes simplex virus (HSV-1) thymidine kinase (TK) and catalytic turnover constants. Fluorinated pyrimidine derivative 12 (40 muM) exhibited better binding affinity for HSV-1 TK than acyclovir (ACV, 170 muM) and ganciclovir (GCV, 48 muM). Catalytic turnover constant (k(cat)) of 12 (0.08 s(-1)) was close to the k(cat) values of ACV (0.10 s(-1)) and GCV (0.10 s(-1)). Furthermore, compounds 8 and 12 showed no cytotoxic effects in HSV-1 TK-transduced and non-transduced cell lines. Besides, compounds 8 and 12 did not exhibit antiviral or cytostatic activities against several viruses and malignant tumor cell lines that were evaluated. The new fluorinated pyrimidine derivative 16 that is phosphorylated by HSV-1 TK could be developed as non-toxic PET-tracer molecule. Thus, F-18 labelling of the precursor 14 was performed by nucleophilic substitution using [F-18] tetrabutylammonium fluoride as the fluorinating reagent.

  DOI：

  10.1081/ncn-200033914
• 作为产物：
  描述：

  2,4-二甲氧基-5,6-二甲基嘧啶 、 苄氧基乙醛 在 正丁基锂 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以63%的产率得到6-(3-benzyloxy-2-hydroxypropyl)-2,4-dimethoxy-5-methylpyrimidine
  参考文献：
  名称：

  Synthesis, ¹⁸F‐Radiolabelling and Biological Evaluations of C‐6 Alkylated Pyrimidine Nucleoside Analogues

  摘要：

  Synthesis of pyrimidine derivatives with a side-chain attached to the C-6 of pyrimidine ring (6-14) is reported. Target compounds 8 and 12 were subjected to in vitro phosphorylation tests, determination of their binding affinities to herpes simplex virus (HSV-1) thymidine kinase (TK) and catalytic turnover constants. Fluorinated pyrimidine derivative 12 (40 muM) exhibited better binding affinity for HSV-1 TK than acyclovir (ACV, 170 muM) and ganciclovir (GCV, 48 muM). Catalytic turnover constant (k(cat)) of 12 (0.08 s(-1)) was close to the k(cat) values of ACV (0.10 s(-1)) and GCV (0.10 s(-1)). Furthermore, compounds 8 and 12 showed no cytotoxic effects in HSV-1 TK-transduced and non-transduced cell lines. Besides, compounds 8 and 12 did not exhibit antiviral or cytostatic activities against several viruses and malignant tumor cell lines that were evaluated. The new fluorinated pyrimidine derivative 16 that is phosphorylated by HSV-1 TK could be developed as non-toxic PET-tracer molecule. Thus, F-18 labelling of the precursor 14 was performed by nucleophilic substitution using [F-18] tetrabutylammonium fluoride as the fluorinating reagent.

  DOI：

  10.1081/ncn-200033914

文献信息

• Synthesis and in vitro antiproliferative evaluation of novel N-alkylated 6-isobutyl- and propyl pyrimidine derivatives
  作者：Tatjana Gazivoda Kraljević、Nataša Ilić、Višnja Stepanić、Lana Sappe、Jasna Petranović、Sandra Kraljević Pavelić、Silvana Raić-Malić

  DOI：10.1016/j.bmcl.2014.04.079

  日期：2014.7

  A series of novel N-alkylated C-6-isobutyl- or -propyl pyrimidine derivatives were synthesized and their antiproliferative effect was evaluated on a panel of tumor cell lines including leukemia cell line K562 and normal diploid human fibroblasts. N-methoxymethylated 5-methylpyrimidin-2,4-dione with di (benzyloxy)isobutyl at C-6 (14b) showed the strongest effect on the cell growth at micromolar concentrations. Mechanisms of action for the lipophilic compound 14b predicted in silico, pointed to its anticancer and antimetastatic potential exerted through inhibition of DNA or RNA polymerases and adhesion molecules. The latter mechanism has been supported in vitro for adherent tumor cell lines. (C) 2014 Elsevier Ltd. All rights reserved.
• Synthesis, ¹⁸F‐Radiolabelling and Biological Evaluations of C‐6 Alkylated Pyrimidine Nucleoside Analogues
  作者：Silvana Raić‐Malić、Anass Johayem、Simon M. Ametamey、Sanja Batinac、Erik De Clercq、Gerd Folkers、Leonardo Scapozza

  DOI：10.1081/ncn-200033914

  日期：2004.1.1

  Synthesis of pyrimidine derivatives with a side-chain attached to the C-6 of pyrimidine ring (6-14) is reported. Target compounds 8 and 12 were subjected to in vitro phosphorylation tests, determination of their binding affinities to herpes simplex virus (HSV-1) thymidine kinase (TK) and catalytic turnover constants. Fluorinated pyrimidine derivative 12 (40 muM) exhibited better binding affinity for HSV-1 TK than acyclovir (ACV, 170 muM) and ganciclovir (GCV, 48 muM). Catalytic turnover constant (k(cat)) of 12 (0.08 s(-1)) was close to the k(cat) values of ACV (0.10 s(-1)) and GCV (0.10 s(-1)). Furthermore, compounds 8 and 12 showed no cytotoxic effects in HSV-1 TK-transduced and non-transduced cell lines. Besides, compounds 8 and 12 did not exhibit antiviral or cytostatic activities against several viruses and malignant tumor cell lines that were evaluated. The new fluorinated pyrimidine derivative 16 that is phosphorylated by HSV-1 TK could be developed as non-toxic PET-tracer molecule. Thus, F-18 labelling of the precursor 14 was performed by nucleophilic substitution using [F-18] tetrabutylammonium fluoride as the fluorinating reagent.