3-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)propanehydrazide | 1446439-57-1

• 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: 3-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)propanehydrazide
• 英文别名: 1-(2-hydrazidoethyl)thymine；3-(5-Methyl-2,4-dioxopyrimidin-1-yl)propanehydrazide
• CAS: 1446439-57-1
• 化学式: C₈H₁₂N₄O₃
• 分子量: 212.208
• InChiKey: VMOXLEDMIRMFDC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)propanehydrazide 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 N-cyclohexyl-3,5-dimethyl-N'-(3-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)propanoyl)benzohydrazide
  参考文献：
  名称：

  Design and synthesis of N-alkyl-N′-substituted 2,4-dioxo-3,4-dihydropyrimidin-1-diacylhydrazine derivatives as ecdysone receptor agonist

  摘要：

  Based on the discovery of thymine as an ecdysteroid agonist, a series of 1,4-disubstituted diacylhydrazine derivatives with a thymine moiety were designed and synthesized. The activities of these compounds against Spodoptera litura (Fabricius) were evaluated by the insect immersion method. Results showed that compound 2h with an N-cyclohexylmethyl substituent exhibits the most potent agonist activity with a median lethal concentration of 23.21 mu g/mL. This compound also caused malformation of molting larvae and adults. Compound 2h was further demonstrated as an ecdysteroid agonist by reporter gene assay on the Spodoptera frugiperda cell line (Sf9 cells). A molecular docking study indicated that hydrophobic interactions and the formation of hydrogen bonds between the compounds and the ecdysone receptor play critical roles in promoting the binding affinity of the compound. The structure of compound 2h may serve as a favorable template for the development of new ecdysteroid agonists with a pyrimidinedione moiety. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.05.010
• 作为产物：
  描述：

  胸腺嘧啶 在 sodium ethanolate 、 一水合肼 作用下， 以 乙醇 为溶剂， 生成 3-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)propanehydrazide
  参考文献：
  名称：

  2-Nucleobase-substituted 4,6-Diaminotriazine Analogs: Synthesis and Anti-cancer Activity in 5-Fluorouracil-sensitive and Resistant Colorectal Cancer Cells

  摘要：

  背景：癌症仍然是全球第二大死因，而结直肠癌（CRC）是第三大最常见的癌症类型。 大肠癌（CRC）是第三大常见癌症。尽管癌症 疗法取得了重大进展，但目前对 CRC 的治疗效果仍不理想。此外，现有的 此外，5-氟尿嘧啶（5-FU）等化疗药物的疗效也受到了 CRC 获得性抗药性的限制。

  方法：在本研究中，我们提供了合成四种新型核酸类似物的创新方法。 类似物。同样，我们还描述了这些化合物对 5G 细胞增殖、迁移、聚集和粘附的影响、 聚合和粘附的影响。 人 CRC 细胞。在这两种细胞类型中，我们合成的新型类似物都能以浓度和时间依赖性方式显著抑制细胞活力。 浓度和时间依赖性。这凸显了这些新型类似物的更高效力。 类似物。此外，这些化合物还抑制了两种细胞类型的迁移和粘附，同时促进了同型细胞-细胞-细胞之间的作用。 它们促进了同型细胞-细胞间的相互作用。 结果：这些变化反映在基质金属蛋白酶（MMP-2 和 MMP-9）的下调。此外，我们的类似物在体内表现出了强大的抗血管生成活性。 结论：这些新型核酸类似物降低了血管内皮生长因子（VEGF）和血管内皮生长因子（VEGF）分泌水平。 生长因子（VEGF）和一氧化氮（NO）的分泌水平。 细胞中的血管内皮生长因子（VEGF）分泌水平和一氧化氮（NO）产生。总之，我们的数据凸显了我们的新 类似物对 CRC（包括 5-FU 耐药型）的潜在化疗特性。

  DOI：

  10.2174/0929867329666220914112042

文献信息

• Spectroscopic Evaluation of Novel Adenine/Thymine-Conjugated Naphthalenediimides: Preference of Adenine-Adenine over Thymine-Thymine Intermolecular Hydrogen Bonding in Adenine- and Thymine-Functionalized Naphthalenediimides
  作者：Digambara Patra、Nadine Al Homsi、Sara Jaafar、Zeina Neouchy、Jomana Elaridi、Ali Koubeissi、Kamal H. Bouhadir

  DOI：10.1007/s10895-018-02340-6

  日期：2019.1

  (adenine/thymine)-conjugated naphthalenediimides (NDIs), namely, NDI-AA, NDI-TT, and NDI-AT have been successfully achieved. NDI-AA, NDI-TT and NDI-AT have similar absorption in the 300–400 nm region. The effect of solvent on the absorption spectrum indicates aggregation, either through intermolecular π-σ interaction among the main chromophore or through intermolecular hydrogen bonding between adenine and adenine group

  已经成功地实现了新型核碱基（腺嘌呤/胸腺嘧啶）-共轭萘二酰亚胺（NDI-AA），NDI-AA和NDI-AT的合成和光谱表征。NDI-AA，NDI-TT和NDI-AT在300-400 nm区域具有相似的吸收。溶剂对吸收光谱的影响表明是通过主要生色团之间的分子间π-σ相互作用或通过腺嘌呤和腺嘌呤基团之间的分子间氢键键合引起的聚集。加水无助于胸腺嘧啶-胸腺嘧啶之间的氢键形成，而是增加溶剂的极性会促进NDI-TT之间的π-σ相互作用。随着温度的升高，NDI-TT的光谱没有变化，这表明氢键在NDI-TT中没有发挥关键作用。对NDI-AA的荧光研究还建立了准分子形成以及基态聚集。随着溶剂混合物中水含量的增加，根据早期结果，由于腺嘌呤-腺嘌呤氢键，不鼓励NDI-AA聚集。同时，NDI-TT发射光谱不会移到蓝色区域，并且535 nm附近的峰强度增加，但以411 nm的荧光为代价。因此，由于胸腺嘧啶-胸腺嘧
• Interactions of Some Divalent Metal Ions with Thymine and Uracil Thiosemicarbazide Derivatives
  作者：Hassan H. Hammud、Mohammad H. El-Dakdouki、Nada Sonji、Ghassan Sonji、Kamal H. Bouhadir

  DOI：10.1080/15257770.2016.1143558

  日期：2016.5.3

  carried out on the interaction of the derivatives towards some divalent metals in 50% v/v ethanol-water containing 0.3 mol.dm−3 KCl, at five different temperatures. The formation constants of the metal complexes for both ligands follow the order: Cu2+ > Ni2+ > Co2+ > Zn2+ > Pb2+ > Cd2+ > Mn2+. The thermodynamic parameters were estimated; the complexation process has been found to be spontaneous, exothermic

  金属离子与核碱基，核苷，核苷酸或核酸之间相互作用的研究已成为化学，生物学和治疗领域的活跃研究领域。在这方面，研究了核碱基衍生物与过渡金属的配位行为，以便更好地了解体外和体内系统中的DNA-金属相互作用。合成了两种核碱基衍生物3-苯甲酰基-1- [3-（胸腺嘧啶-1-基）丙]硫脲和3-苯甲酰基-1- [3-（尿嘧啶-1-基）丙酰胺]硫脲及其解离常数在不同温度和0.3离子强度下测定。在含0.3 mol.dm -3的50％v / v乙醇-水中，对衍生物与某些二价金属的相互作用进行了电位测定研究。氯化钾，在五个不同的温度下。两个配体的金属配合物的形成常数遵循以下顺序：Cu 2+ > Ni 2+ > Co 2+ > Zn 2+ > Pb 2+ > Cd 2+ > Mn 2+。估算热力学参数；已经发现络合过程是自发的，放热的并且是熵有利的。
• Novel carbocyclic nucleoside analogs suppress glomerular mesangial cells proliferation and matrix protein accumulation through ROS-dependent mechanism in the diabetic milieu. II. Acylhydrazone-functionalized pyrimidines
  作者：Kamal H. Bouhadir、Ali Koubeissi、Fatima A. Mohsen、Mira Diab El-Harakeh、Rouba Cheaib、Joan Younes、Georges Azzi、Assaad A. Eid

  DOI：10.1016/j.bmcl.2015.12.042

  日期：2016.2

  We report herein the synthesis of a novel series of carbocyclic acylhydrazone derivatives of uracil, thymine and cytosine from the corresponding nucleic bases and their biological activity to treat diabetic nephropathy. Intriguingly, five derivatives significantly reduced high-glucose induced glomerular mesangial cells proliferation and matrix protein accumulation in vitro. The anti-oxidative effects displayed by these molecules suggest that their activity might involve a ROS-dependent mechanism. (C) 2015 Elsevier Ltd. All rights reserved.
• Design and synthesis of N-alkyl-N′-substituted 2,4-dioxo-3,4-dihydropyrimidin-1-diacylhydrazine derivatives as ecdysone receptor agonist
  作者：Xiu Liu、Ling Zhang、Jin-Guo Tan、Han-Hong Xu

  DOI：10.1016/j.bmc.2013.05.010

  日期：2013.8

  Based on the discovery of thymine as an ecdysteroid agonist, a series of 1,4-disubstituted diacylhydrazine derivatives with a thymine moiety were designed and synthesized. The activities of these compounds against Spodoptera litura (Fabricius) were evaluated by the insect immersion method. Results showed that compound 2h with an N-cyclohexylmethyl substituent exhibits the most potent agonist activity with a median lethal concentration of 23.21 mu g/mL. This compound also caused malformation of molting larvae and adults. Compound 2h was further demonstrated as an ecdysteroid agonist by reporter gene assay on the Spodoptera frugiperda cell line (Sf9 cells). A molecular docking study indicated that hydrophobic interactions and the formation of hydrogen bonds between the compounds and the ecdysone receptor play critical roles in promoting the binding affinity of the compound. The structure of compound 2h may serve as a favorable template for the development of new ecdysteroid agonists with a pyrimidinedione moiety. (C) 2013 Elsevier Ltd. All rights reserved.
• 2-Nucleobase-substituted 4,6-Diaminotriazine Analogs: Synthesis and Anti-cancer Activity in 5-Fluorouracil-sensitive and Resistant Colorectal Cancer Cells
  作者：Kamal Bouhadir、Ali H. Eid、Khalil Hamze、Rola H. Abdallah、Nour K Younis、Manal Fardoun、Nadine Darwiche、Firas Kobeissy、Rabah Iratni

  DOI：10.2174/0929867329666220914112042

  日期：2023.8

  Cancer continues to be the second leading cause of death worldwide, with colorectal cancer (CRC) being the third most common type. Despite significant advances in cancer therapies, the current treatment of CRC remains suboptimal. In addition, the effectiveness of available chemotherapeutic drugs such as 5-Fluorouracil (5-FU) is limited by CRC-acquired resistance.

  In this study, we provide innovative approaches employed in synthesizing four novel nucleobase analogs. Equally, we describe the effects of these compounds on proliferation, migration, aggregation, and adhesion of 5-FU-sensitive (HCT116) and -resistant (5-FU-R-HCT116) human CRC cells. In either cell type, our synthesized novel analogs significantly inhibited cell viability in a concentration- and time-dependent manner. This highlights the higher potency of these novel analogs. In addition, these compounds attenuated migration and adhesion of both cell types while they promoted homotypic cell-cell interaction.

  These changes were reflected by the downregulation of matrix metalloproteases (MMP-2 and MMP-9). Furthermore, our analogs exhibited potent anti-angiogenic activity in vivo.

  These novel nucleobase analogs reduced the level of secreted vascular endothelial growth factor (VEGF) and nitric oxide (NO) production in both 5-FU-sensitive and -resistant CRC cells. Taken together, our data highlight the potential chemotherapeutic properties of our novel analogs against CRC, including the 5-FU-resistant form.

  背景：癌症仍然是全球第二大死因，而结直肠癌（CRC）是第三大最常见的癌症类型。 大肠癌（CRC）是第三大常见癌症。尽管癌症 疗法取得了重大进展，但目前对 CRC 的治疗效果仍不理想。此外，现有的 此外，5-氟尿嘧啶（5-FU）等化疗药物的疗效也受到了 CRC 获得性抗药性的限制。

  方法：在本研究中，我们提供了合成四种新型核酸类似物的创新方法。 类似物。同样，我们还描述了这些化合物对 5G 细胞增殖、迁移、聚集和粘附的影响、 聚合和粘附的影响。 人 CRC 细胞。在这两种细胞类型中，我们合成的新型类似物都能以浓度和时间依赖性方式显著抑制细胞活力。 浓度和时间依赖性。这凸显了这些新型类似物的更高效力。 类似物。此外，这些化合物还抑制了两种细胞类型的迁移和粘附，同时促进了同型细胞-细胞-细胞之间的作用。 它们促进了同型细胞-细胞间的相互作用。 结果：这些变化反映在基质金属蛋白酶（MMP-2 和 MMP-9）的下调。此外，我们的类似物在体内表现出了强大的抗血管生成活性。 结论：这些新型核酸类似物降低了血管内皮生长因子（VEGF）和血管内皮生长因子（VEGF）分泌水平。 生长因子（VEGF）和一氧化氮（NO）的分泌水平。 细胞中的血管内皮生长因子（VEGF）分泌水平和一氧化氮（NO）产生。总之，我们的数据凸显了我们的新 类似物对 CRC（包括 5-FU 耐药型）的潜在化疗特性。