6-<<2-<1,3-bis(benzyloxy)-2-hydroxypropyl>>methyl>-2,4-dimethoxy-5-methylpyrimidine | 139871-31-1

• 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-<<2-<1,3-bis(benzyloxy)-2-hydroxypropyl>>methyl>-2,4-dimethoxy-5-methylpyrimidine
• 英文别名: 6-<3-benzyloxy-2-<(benzyloxy)methyl>-2-hydroxypropyl>-2,4-dimethoxy-5-methylpyrimidine；6-(3-benzyloxy)-2-(benzyloxymethyl-2-hydroxypropyl)-2,4-dimethoxy-5-methylpyrimidine；6-(3-benzyloxy-2-(benzyloxymethyl)-2-hydroxypropyl)-5-methyl-2,4-dimethoxypyrimidine；6-[(3-benzyloxy-2-benzyloxymethyl-2-hydroxy)propyl]-5-methyl-2,4-dimethoxypyrimidine；1,3-bis(benzyloxy)-2-[(2,6-dimethoxy-5-methylpyrimidin-4-yl)methyl]propan-2-ol；6-[(3-benzyloxy-2-benzyloxymethyl-2-hydroxy)propyl]-2,4-dimethoxy-5-methylpyrimidine；1-(2,6-Dimethoxy-5-methylpyrimidin-4-yl)-3-phenylmethoxy-2-(phenylmethoxymethyl)propan-2-ol
• CAS: 139871-31-1
• 化学式: C₂₅H₃₀N₂O₅
• 分子量: 438.524
• InChiKey: DKCLRPDKFUGDNB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  32
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  82.9
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-<<2-<1,3-bis(benzyloxy)-2-hydroxypropyl>>methyl>-2,4-dimethoxy-5-methylpyrimidine 在 4-二甲氨基吡啶 、 偶氮二异丁腈 、 三正丁基氢锡 、 三氯化硼 、 potassium carbonate 、 三乙胺 、 乙酰氯 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 4.0h， 生成 6-[3-hydroxy-2-(4-methoxytriphenylmethoxymethyl)propyl]-1-methoxymethyl-5-methylpyrimidin-2,4-dione
  参考文献：
  名称：

  带有 C-6 无环侧链的嘧啶的甲氧基甲基 (MOM) 基团氮保护。

  摘要：

  合成了新型 N-甲氧基甲基化 (MOM) 嘧啶 (4-13) 和嘧啶-2,4-二酮 (15-17) 核苷模拟物，其中异丁基侧链连接在嘧啶部分的 C-6 位置。已经评估了通过 O-过甲硅烷基化或 N-阴离子尿嘧啶衍生物的合成方法合成具有 C-6 无环侧链的 N-1-和/或 N-3-MOM 嘧啶衍生物。使用活化的 N-阴离子嘧啶衍生物的合成方法以良好的产率提供了所需的 N,N-1,3-diMOM 和 N-1-MOM 嘧啶 4 和 5。用 DAST 作为氟化试剂将氟引入侧链，得到在 C-6 处具有 1-氟-3-羟基异丁基部分的 N,N-1,3-diMOM 嘧啶 13。使用 NOE 实验对单三苯甲基化 N-1-MOM 嘧啶 12 的构象研究表明，该化合物的主要构象是 C-6 侧链中的羟甲基靠近 N-1-MOM部分，而 OMTr 靠近 CH(3)-5 基团。与此相反，没有观察到 N-1-MOM 基团与

  DOI：

  10.3390/molecules16065113
• 作为产物：
  描述：

  2,4-二氯-5,6-二甲基嘧啶 在 甲醇 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正庚烷 、 乙基苯 为溶剂， 反应 3.0h， 生成 6-<<2-<1,3-bis(benzyloxy)-2-hydroxypropyl>>methyl>-2,4-dimethoxy-5-methylpyrimidine
  参考文献：
  名称：

  C(6)-异丁基-和C(6)-异丁烯基-取代的嘧啶和二氢吡咯并[1,2-c]嘧啶-1,3-二酮的合成和抗肿瘤评价

  摘要：

  越来越多的证据支持嘧啶衍生物，其中糖残基已被无环侧链取代，可能被开发为有前途的抗癌剂，干扰肿瘤细胞增殖、存活和转移形成。在这项工作中，我们在 C(6) 处制备了带有 i-Bu（即 3、4 和 7-9）和异丁烯基（即 5 和 10）侧链的新型嘧啶，并检查了它们对肿瘤细胞系的体外作用. 二氢吡咯并[1,2-c]嘧啶-1,3-二酮6和11是分子内环化的产物，发生在5中的Bn或10中的MeO保护基团的去除过程中。用二乙氨基三氟化硫氟化3（ DAST)，然后将所得氟化衍生物 4 脱卤化氢得到具有 C(2')C(3') 键的 6-异丁-2'-烯基嘧啶衍生物 5。为了制备 6-isobut-1'-en-1-yl pyrimidine 10，应用了一种涉及 1,3-二醇乙酰化的合成策略。化合物 3-11 的抗肿瘤评估表明，含有 6-[(1,3-二苄氧基)-2-羟基] 甲基侧链 3 的 2,4-二甲氧基嘧

  DOI：

  10.1002/cbdv.201000202

文献信息

• [EN] NEW 6-SUBSTITUTED PYRIMIDINE DERIVATIVES<br/>[FR] NOUVEAUX DÉRIVÉS DE PYRIMIDINE 6-SUBSTITUÉS
  申请人：SVEUCILISTE U ZAGREBU

  公开号：WO2011036505A1

  公开（公告）日：2011-03-31

  The Invention deals with new 6-substituted pyrimidine derivatives of the general formula (I): where: R1 = methyl or H or CH2X, X = Br, F, Cl R2 = oxygen or methoxy or OH R3 = oxygen or methoxy or OH R4 = H or methyl or (CH2)nY, n = 2 or 3, Y = OH or Br or F or Cl or OCOCH3, R5 = (II), (III), R6 and R7 can independently of each other be H, CH2Z, CH2OH, CH2OCH2Ph, CH2OCPh2PhOCH3; Z=Br, F, Cl; Where, if R5 = (IV) and if one of R6 and R7 CH2Z (Z = Br, F, Cl), then R5 and R1 form with CH2A, A = Cl, Br, F a substituted unsaturated 5-membered ring and, provided that R6 or R7 = H, then the other of them cannot be H; and R8, R9, R10 = OH, CH2OCH2Ph, H, OC2O3CH3, CH2OH, CH2OCPh2PhOCH3, CH2OSO2PhCH3; and where F, regardless of which place it may take in the molecule, may appear in the form of radioisotope 18F; one of the carbons occupying any place in the compound of the general formula I may appear in the form of radioisotope 11C, just as an oxygen occupying any place in the compound of the general formula I may appear in the form of radioisotope 15O; the Invention also deals with their use as substrates in the Positron Emission Tomography (PET), as well as their use in tumor therapy. Formulae (I), (II), (III), (IV)

  该发明涉及一般式(I)的新6-取代嘧啶衍生物，其中：其中：R1 = 甲基或H或CH2X，X = Br，F，Cl R2 = 氧或甲氧基或OH R3 = 氧或甲氧基或OH R4 = H或甲基或(CH2)nY，n = 2或3，Y = OH或Br或F或Cl或OCOCH3，R5 = (II)，(III)，R6和R7可以彼此独立地为H，CH2Z，CH2OH，CH2OCH2Ph，CH2OCPh2PhOCH3；Z = Br，F，Cl；其中，如果R5 = (IV)并且如果R6和R7中的一个为CH2Z（Z = Br，F，Cl），则R5和R1与CH2A形成取代的不饱和5-成员环，A = Cl，Br，F，前提是R6或R7 = H，则另一个不能为H；而R8，R9，R10 = OH，CH2OCH2Ph，H，OC2O3CH3，CH2OH，CH2OCPh2PhOCH3，CH2OSO2PhCH3；F无论在分子的哪个位置，都可以以放射同位素18F的形式出现；一般式I的化合物中占据任何位置的碳原子之一可以以放射同位素11C的形式出现，就像一般式I的化合物中占据任何位置的氧可以以放射同位素15O的形式出现；该发明还涉及它们作为正电子发射断层扫描（PET）中的底物的用途，以及它们在肿瘤治疗中的用途。公式(I)，(II)，(III)，(IV)
• Syntheses and Antitumor Evaluation of C(6)-Isobutyl- and C(6)-Isobutenyl-Substituted Pyrimidines, and Dihydropyrrolo[1,2-c]pyrimidine-1,3-diones
  作者：Svjetlana Krištafor、Tatjana Gazivoda Kraljević、Simon M. Ametamey、Mario Cetina、Ivana Ratkaj、Romana Tandara Haček、Sandra Kraljević Pavelić、Silvana Raić-Malić

  DOI：10.1002/cbdv.201000202

  日期：2011.8

  A growing body of evidence supports that pyrimidine derivatives, in which the sugar residues have been replaced by acyclic side chains, might be developed as promising anticancer agents that interfere with tumor cell proliferation, survival, and metastatic formation. In this work, we prepared novel pyrimidines bearing i‐Bu (i.e., 3, 4, and 7–9) and isobutenyl (i.e., 5 and 10) side chains at C(6) and

  越来越多的证据支持嘧啶衍生物，其中糖残基已被无环侧链取代，可能被开发为有前途的抗癌剂，干扰肿瘤细胞增殖、存活和转移形成。在这项工作中，我们在 C(6) 处制备了带有 i-Bu（即 3、4 和 7-9）和异丁烯基（即 5 和 10）侧链的新型嘧啶，并检查了它们对肿瘤细胞系的体外作用. 二氢吡咯并[1,2-c]嘧啶-1,3-二酮6和11是分子内环化的产物，发生在5中的Bn或10中的MeO保护基团的去除过程中。用二乙氨基三氟化硫氟化3（ DAST)，然后将所得氟化衍生物 4 脱卤化氢得到具有 C(2')C(3') 键的 6-异丁-2'-烯基嘧啶衍生物 5。为了制备 6-isobut-1'-en-1-yl pyrimidine 10，应用了一种涉及 1,3-二醇乙酰化的合成策略。化合物 3-11 的抗肿瘤评估表明，含有 6-[(1,3-二苄氧基)-2-羟基] 甲基侧链 3 的 2,4-二甲氧基嘧
• Synthesis, Crystal Structure, and in Vitro Biological Evaluation of C-6 Pyrimidine Derivatives: New Lead Structures for Monitoring Gene Expression in Vivo
  作者：Miljen Martić、Lucile Pernot、Yvonne Westermaier、Remo Perozzo、Tatjana Gazivoda Kraljević、Svjetlana Krištafor、Silvana Raić-Malić、Leonardo Scapozza、Simon Ametamey

  DOI：10.1080/15257770.2011.581258

  日期：2011.4

  Novel C-6 substituted pyrimidine derivatives are good substrates of herpes simplex virus type 1 thymidine kinase (HSV1-TK). Enzyme kinetic experiments showed that our lead compound, N-methyl DHBT (N-methyl-6-(1,3-dihydroxyisobutyl) thymine; N-Me DHBT), is phosphorylated at a similar rate compared to ogold standardo 9-[4-fluoro-3-(hydroxymethyl)butyl]guanine, FHBG, (Km = 10 +/- 0.3 M; kcat = 0.036 +/- 0.015 sec-1). Additionally, it does not show cytotoxic properties on B16F1 cells up to a concentration of 10 mM. The x-ray analysis of the crystal structures of HSV1-TK with N-Me DHBT and of HSV1-TK with the fluorinated derivative N-Me FHBT confirmed the binding mode predicted by docking studies and their substrate characteristics. Moreover, the crystal structure of HSV1-TK with N-Me DHBT revealed an additional water-mediated H-bond interesting for the design of further analogues.
• 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 of C-6 Pyrimidine Acyclic Nucleoside Analogs as Potential Antiviral Agents
  作者：Ling-Yih Hsu、Dean S. Wise、William M. Shannon、John C. Drach、Leroy B. Townsend

  DOI：10.1080/15257779408013263

  日期：1994.3

  A number of pyrimidine acyclic nucleosides in which the acyclic moiety is attached to the C-6 position rather than N-1 of the pyrimidine ring have been prepared. This was accomplished via treatment of lithiated 2,4-methoxy-5,6-dimethylpyrimidine, or, 2,4-dimethoxy-6-methylpyrimidine with 1,3-bis-(benzyloxy)-2-propanone, benzyl chloromethyl ether or oxirane, respectively, to give the corresponding key intermediates 6-[3-benzyloxy-2-[(benzyloxy)methyl]-2-hydroxypropyl]-2,4- dimethoxy-5-methylpyrimidine (2a), 6-[3-benzyloxy-2-[(benzyloxy)methyl]-2-hydroxypropyl]-2,4-dimethoxypyrimidine (2b), 6-(2-benzyloxyethyl)-2,4-dimethoxy-5-methylpyrimidine (3), and 2,4-dimethoxy-6-(3-hydroxypropyl)-5-methylpyrimidine (4a). After acidic hydrolysis, followed by debenzylation with boron trichloride these key intermediates were converted to the target C-6 pyrimidine acyclic derivatives. Compounds 6-8b, 11-13, 15, 16, 20, 22, 26, and 29-32 were evaluated for activity against herpes viruses and human immunodeficiency virus. None of the compounds were active against the viruses nor were they cytotoxic at the highest concentration tested.