1-(benzyloxy)-4-(1′,2′,4′-triazol-1′-yl)-2-(1H)-pyrimidinone | 219992-65-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 1-(benzyloxy)-4-(1′,2′,4′-triazol-1′-yl)-2-(1H)-pyrimidinone
• 英文别名: 1-(benzyloxy)-4-(1',2',4'-triazol-1'-yl)-2(1H)-pyrimidinone；1-benzyloxy-4-(1',2',4'-triazol-1'-yl)-2(1H)-pyrimidinone；1-benzyloxy-4-(1,2,4-triazol-1-yl)pyrimidin-2(1H)-one；1-bezyloxy-4-(1,2,4-triazol-1-yl)-2(1H)-pyrimidinone；1-(benzyloxy)-4-(1,2,4-triazol-1-yl)-2(1H)-pyrimidinone；1-Phenylmethoxy-4-(1,2,4-triazol-1-yl)pyrimidin-2-one
• CAS: 219992-65-1
• 化学式: C₁₃H₁₁N₅O₂
• 分子量: 269.263
• InChiKey: ALZDALVFFODXSB-UHFFFAOYSA-N

物化性质

• 熔点：
  202-205 °C
• 沸点：
  493.6±38.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  72.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(benzyloxy)-4-(1′,2′,4′-triazol-1′-yl)-2-(1H)-pyrimidinone 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 20.0h， 生成 4-(3-Aminopropylamino)-1-(benzyloxy)-2(1H)-pyrimidinone hydrochloride
  参考文献：
  名称：

  一种用于三价硬金属离子的新型三脚架Tris-羟基嘧啶酮螯合剂：合成，络合和体内研究†

  摘要：

  一种新的三足六齿配体NTP（PrHPM）3，具有三个羟基嘧啶酮已经制备并研究了与次氮基三丙酸（NTP）结合的（HPM）螯合单元，并研究了与铁，铝和镓的配合物的热力学稳定性，随后对其进行了体内分析以从中去除硬金属离子的能力。重达67 Ga的动物模型。将HPM单位锚固到NTP支架上，是报道的六齿三（3-羟基-4-吡啶酮）类似物NTP（PrHP）3的有趣替代品，因为新的tris- HPM配体仍保持对硬金属离子的高螯合能力，并具有更好的水溶性（log P = −1.51）。在体内的研究表明，NTP（PrHPM）3与市售药物，DFP或双齿HPM化合物（HOPY-PrN）相比，诱导从主要器官清除的速度更快，总体排泄量增加，尽管比三羟基吡啶酮类似物NTP（PrHP）3略低。本文提出的解决方案和体内结果鼓励了进一步的研究，设想了六齿HPM衍生物作为金属螯合剂的潜在临床应用。

  DOI：

  10.1039/c2dt32361c
• 作为产物：
  描述：

  N-(苄氧基)脲 在 三乙胺 、 三氯氧磷 作用下， 以 二甲基亚砜 为溶剂， 反应 22.0h， 生成 1-(benzyloxy)-4-(1′,2′,4′-triazol-1′-yl)-2-(1H)-pyrimidinone
  参考文献：
  名称：

  Synthesis of N-1-oxypyrimidine 1,3-dioxolane and 1,3-oxathiolane nucleosides

  摘要：

  合成了两组含有N-1-氧代嘧啶的1,3-二氧戊环和1,3-氧硫杂环戊烷核苷，作为潜在的抗病毒药物。

  DOI：

  10.1039/b006600l

文献信息

• New hydroxypyrimidinone-containing sulfonamides as carbonic anhydrase inhibitors also acting as MMP inhibitors
  作者：M. Alexandra Esteves、Osvaldo Ortet、Anabela Capelo、Claudiu T. Supuran、Sérgio M. Marques、M. Amélia Santos

  DOI：10.1016/j.bmcl.2010.04.109

  日期：2010.6

  (BSA) derivatives bearing a hydroxypyrimidinone (HPM) moiety were synthesized and investigated for their inhibitory activity against several carbonic anhydrase (CA, EC 4.2.1.1) isozymes. They all revealed to be very potent inhibitors (nanomolar order) of the cytosolic CA I and II isozymes, but especially of the transmembrane, tumor-associated CA IX isozyme, a beneficial feature for a potential antitumor

  合成了一组带有羟基嘧啶酮（HPM）部分的苯磺酰胺（BSA）衍生物，并研究了它们对几种碳酸酐酶（CA，EC 4.2.1.1）同工酶的抑制活性。它们都显示出是胞质CA I和II同工酶的非常有效的抑制剂（纳摩尔级），但尤其是跨膜的，与肿瘤相关的CA IX同工酶，对这些化合物具有潜在的抗肿瘤作用是有益的。旨在改善CA抑制特异性和增强其基质金属蛋白酶（MMP）抑制活性的进一步结构优化也可能导致具有抗肿瘤剂双重作用机理的新型化合物。
• New hexadentate ligands composed of 1-hydroxy-2(1H )-pyrimidinone, α,ω-diamine and 1,1,1-tris(carboxyethoxymethyl)ethane or tri(carboxybutyl)isocyanurate. Synthesis and characterization of their iron(III) complexes
  作者：Akira Katoh、Yoko Hida、Jun Kamitani、Junko Ohkanda

  DOI：10.1039/a807159d

  日期：——

  The successive coupling of 1-benzyloxy-2(1H)-pyrimidinone with α,ω-diamines, 1,1,1-tris(carboxyethoxymethyl)ethane or tri(carboxybutyl)isocyanurate, and final removal of the benzyl protecting group afforded new hexadentate ligands (TEPOHn or TCPOH). The UV/VIS spectroscopic analysis in aqueous solution indicated 1∶1 stoichiometric complexation of the hexadentate ligand with iron(III). The relative stability constants of iron(III) complexes of the hexadentate ligands were estimated to be log K 24.4–26.3 by the competitive reaction with EDTA, suggesting that the stability was affected by the methylene chain length. The standard redox potential E1/2 of Fe(TEPO2) was measured to be –493 mV at apparent pH 8.0 in 50% aqueous DMF solution. This value was approximately 300 mV higher than that of the iron(III) complex of natural desferrioxamine B (DFB). Further, all synthetic hexadentate ligands effectively removed 3–6 times as much iron(III) from human transferrin as DFB even though the ratio of the synthetic ligand to transferrin was one-fifth that of DFB.

  将 1-苄氧基-2(1H)-嘧啶酮与δ,Ï-二胺、1,1,1-三(羧基乙氧基甲基)乙烷或三(羧基丁基)异氰脲酸酯连续偶联，并最终去除苄基保护基，可得到新的六价配体（TEPOHn 或 TCPOH）。水溶液中的紫外/可见光谱分析表明，六价配体与铁（III）的络合度为 1:1。通过与乙二胺四乙酸（EDTA）的竞争反应，六价配体的铁（III）络合物的相对稳定常数估计为 log K 24.4â26.3 ，这表明稳定性受到亚甲基链长度的影响。在50%的DMF水溶液中，表观pH值为8.0时，测得Fe(TEPO2)的标准氧化还原电位E1/2为493 mV。这一数值比天然去铁胺B（DFB）的铁（III）络合物高出约300 mV。此外，尽管合成配体与转铁蛋白的比例只有DFB的五分之一，但所有合成六价配体从人体转铁蛋白中清除铁（III）的效果都是DFB的3.6倍。
• Synthesis and Metal‐Complexation Properties of a New Hydroxypyrimidinone‐Functionalized Sepharose
  作者：M. Alexandra Esteves、Anabela Cachudo、Sílvia Chaves、M. Amélia Santos

  DOI：10.1002/ejic.200400355

  日期：2005.2

  and complexation properties towards a set of metal ions (FeIII, AlIII, and ThIV) were studied by potentiometry and spectrophotometry. The ligand was further immobilized in an epoxy-activated sepharose by chemical coupling through the aminoalkyl pendent group with the aim of improving its sequestering capacity for residual amounts of metals. The new hydroxypyrimidinone-functionalized sepharose shows

  合成了1-羟基-2-(1H)-嘧啶酮衍生物4-(3-氨基丙基氨基)-1-羟基-2-(1H)-嘧啶酮(HOPY-PrN)，并对其酸碱和络合性质进行了研究通过电位测定法和分光光度法研究了金属离子（FeIII、AlIII 和 ThIV）的浓度。配体通过氨基烷基侧基化学偶联进一步固定在环氧活化的琼脂糖凝胶中，目的是提高其对残留金属量的螯合能力。新的羟基嘧啶酮功能化琼脂糖凝胶在 pH 3-8 范围内对金属离子显示出高螯合能力，因此为潜在的环境应用提供了良好的前景。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
• Synthesis of Linear and Cyclic Hexapeptides with Ne-(1,2-Dihydro-1-hydroxy-2-oxopyrimidin-4-yl)-L-lysyl-b-alanyl as the Repeating Unit and Properties of Their Iron(III) Complexes
  作者：Akira Katoh、Yuichi Inoue、Hitoshi Nagashima、Yasushi Hikita、Junko Ohkanda、Ryota Saito

  DOI：10.3987/com-02-s(m)34

  日期：——

  Linear and cyclic hexapeptides including N-epsilon(1,2-dihydro-1hydroxy-2-oxopyrimidin-4-yl)-L-lysyl-beta-alanyl as the repeating unit have been synthesized. These hexapeptides formed 1:1 iron(III) complexes; lambda(max) 466 nm and epsilon 4700 for a linear hexapeptide (8), and lambdamax 458 nm and epsilon 4300 for a cyclic hexapeptide (9). The relative stability constants of 8- and 9-iron(III) complexes were estimated to be 26.1 and 28.0, respectively. A linear hexapeptide (8)iron(III) complex predominantly existed in Delta-configuration. From kinetic data on iron(III) removal from human transferrin, a linear hexapeptides (8) was found to efficiently remove three times as much iron(III) from transferrin as desferrioxamine B, only a chemotherapeutic agent for the iron overload disease.
• Novel Iron Sequestering Agents:  Synthesis and Iron-Chelating Properties of Hexadentate Ligands Composed of 1-Hydroxy-2(1<i>H</i>)-pyrimidinone, ω-Amino Carboxylic Acid, and Tris(2-aminoethyl)amine
  作者：Junko Ohkanda、Jun Kamitani、Takeshi Tokumitsu、Yoko Hida、Takeo Konakahara、Akira Katoh

  DOI：10.1021/jo961901m

  日期：1997.5.1

  Novel heterocyclic hexadentate ligands (3HOPY(n): n = 5-7), in which three units of 1-hydroxy-2(1H)-pyrimidinone are linked to tris(2-aminoethyl)amine through an amide bond by an alkyl chain, were synthesized, and their iron-chelating properties were investigated. The stability of their iron complexes (25 to 27 in log K) was significantly larger than that of pyrazinone-containing ligands by virtue of higher pK(a) values. On kinetic evaluation of iron removal from human transferrin, 3HOPY(5) showed remarkable efficiency over five times as much as commercially available desferrioxamine B. The conformational analysis of the corresponding Ga(III) complex of Fe(opy(5)) by H-1 NMR and by MM and MD calculations are also discussed.