1-phenyl-2-thioxodihydropyrimidine-4,6(1H,5H)dione | 15112-10-4

• 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: 1-phenyl-2-thioxodihydropyrimidine-4,6(1H,5H)dione
• 英文别名: 1-phenyl-2-thiobarbituric acid；1-phenyl-2-thioxo-dihydro-pyrimidine-4,6-dione；1-phenyl-2-thio-barbituric acid；1-Phenyl-2-thio-barbitursaeure；1-Phenylthiobarbitursaeure；1-phenyl-2-thioxodihydropyrimidine-4,6(1H,5H)-dione；1-phenyl-2-sulfanylidene-1,3-diazinane-4,6-dione
• CAS: 15112-10-4
• 化学式: C₁₀H₈N₂O₂S
• mdl: MFCD01216983
• 分子量: 220.252
• InChiKey: NPXACSUWYDROMZ-UHFFFAOYSA-N

物化性质

• 密度：
  1.45±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  81.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-phenyl-2-thioxodihydropyrimidine-4,6(1H,5H)dione 在 三乙胺 、 sodium hydroxide 、 三氯氧磷 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.17h， 生成 5-((3aS,4S,6aR)-3a,6a-dimethyl-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)-N-(6-((2-((2-(naphthalen-2-ylamino)-2-oxoethyl)thio)-6-oxo-1-phenyl-1,6-dihydropyrimidin-4 yl)amino)hexyl)pentanamide
  参考文献：
  名称：

  Strategy and validation of a structure-based method for the discovery of selective inhibitors of PAK isoforms and the evaluation of their anti-cancer activity

  摘要：

  p21 activated kinase 4 (PAK4), which belongs to the serine/threonine (Ser/Thr) protein kinase family, is a representative member of the PAK family and plays a significant role in multiple processes associated with cancer development. In this study, structure-based virtual screening was performed to discover novel and selective small molecule scaffolds, and a 6-hydroxy-2-mercapto-3-phenylpyrimidin-4(3H)-one-based compound (SPU-106, 14#) was identified as an effective PAK4 inhibitor. By combining both a molecular docking study and molecular dynamics (MD) simulation strategies, the binding mode was determined in the PAK4 site. The SPU-106 compound could efficiently and selectively bind to the PAK4 kinase domain at an IC50 of 21.36 mu M according to the kinase analysis. The designed molecular probe demonstrated that SPU-106 binds to the kinase domain in the C-terminus of PAK4. Further investigation revealed that the SPU-106 had a strong inhibitory effect on the invasion of SGC7901 cells but without any cytotoxicity. The western blot analysis indicated that the compound potently inhibited the PAK4/LIMK1/cofilin and PAK4/SCG10 signaling pathways. Thus, our work shows the successful application of computational strategies for the discovery of selective hits, and SPU-106 may be an effective PAK4 inhibitor for further development as an antitumor agent.

  DOI：

  10.1016/j.bioorg.2019.103168
• 作为产物：
  描述：

  6-amino-N₁-phenyl-2-thiouracil 在 硫酸 作用下， 生成 1-phenyl-2-thioxodihydropyrimidine-4,6(1H,5H)dione
  参考文献：
  名称：

  L'acide p-Diméthylaminobenzylidènethiobarbiturique et ses dérivés dans la recherche des métaux nobles

  摘要：

  DOI：

  10.1016/s0003-2670(00)87305-5

文献信息

• Experimental and theoretical investigations on the tautomerism of 1-phenyl-2-thiobarbituric acid and its methylation reaction
  作者：Gang Wang、Jian Wang、Han Nie、Shen-Peng Tan、Wei-Qun Shi、Dong-Mei Zhao、Mao-Sheng Cheng

  DOI：10.1016/j.molstruc.2012.12.017

  日期：2013.3

  geometry optimization of eight possible tautomers of 1-phenyl-2-thiobarbituric acid was performed in gas phase and in different solvents using COSMO method. The calculated results are in good accordance with experimental data. Additionally, the methylation reaction of 1-phenyl-2-thiobarbituric acid was investigated for the first time by combination of experimental and theoretical methods. The methylation

  在本研究中，合成了 1-苯基-2-硫代巴比妥酸 (1)，并通过 FT-IR 光谱、X 射线分析和 H-1 核磁共振研究以及量子化学计算研究了该化合物的互变异构现象。发现化合物 1 在固态和 CDCl3 溶液中以三酮形式存在，而在 DMSO-d(6)、DMF-d(7) 和 CD3OD 溶液中观察到互变异构。使用 COSMO 方法在气相和不同溶剂中对 1-苯基-2-硫代巴比妥酸的八种可能互变异构体进行几何优化。计算结果与实验数据吻合良好。此外，首次结合实验和理论方法研究了1-苯基-2-硫代巴比妥酸的甲基化反应。由于 1-苯基-2-硫代巴比妥酸的结构特征，甲基化产物可能因三种可能的异构体而异。我们通过X射线衍射和FT-IR光谱对得到的甲基化产物进行鉴定，并进行过渡态搜索和能量计算以阐明实验数据，结果表明理论计算与实验数据一致。(c) 2012 Elsevier BV 版权所有。
• Non-linear optically active molecules, their synthesis, and use
  申请人：McGinniss D. Vincent

  公开号：US20080004415A1

  公开（公告）日：2008-01-03

  In one aspect, the present invention provides a hyperpolarizable organic chromophore. The chromophore is a nonlinear optically active compound that includes a π-donor conjugated to a π-acceptor through a π-electron conjugated bridge. In other aspects of the invention, donor structures and acceptor structures are provided. In another aspect of the invention, a chromophore-containing polymer is provided. In one embodiment, the chromophore is physically incorporated into the polymer to provide a composite. In another embodiment, the chromophore is covalently bonded to the polymer, either as a side chain polymer or through crosslinking into the polymer. In other aspects, the present invention also provides a method for making the chromophore, a method for making the chromophore-containing polymer, and methods for using the chromophore and chromophore-containing polymer.

  在一个方面，本发明提供了一种高极化有机色团。该色团是一种非线性光学活性化合物，包括一个π-给体通过一个π-电子共轭桥连接到一个π-受体上。在本发明的其他方面，提供了给体结构和受体结构。在发明的另一个方面，提供了含有色团的聚合物。在一种实施例中，色团被物理地并入聚合物中以提供复合材料。在另一种实施例中，色团通过侧链聚合物或交联到聚合物中与聚合物共价键合。在其他方面，本发明还提供了制备色团的方法、制备含有色团的聚合物的方法以及使用色团和含有色团的聚合物的方法。
• Analytical studies on pyrimidine derivatives. VI. Sensitive spectrophotometric determination of gold(III) by solvent extraction with 5-p-dimethylaminocinnamylidene-1-phenyl-2-thiobarbituric acid.
  作者：KENICHIRO NAKASHIMA、SHUZO AKIYAMA

  DOI：10.1248/cpb.29.1755

  日期：——

  A sensitive spectrophotometric method for the determination of gold (III) with 5-p-dimethylaminocinnamylidene-1-phenyl-2-thiobarbituric acid (DACTB) is described. DACTB reacts easily with gold (III), forming a blue complex in diluted hydrochloric acid which can be extracted with chloroform. The chloroform solution of the complex has an absorption maximum at 622 nm against a reagent blank and shows a constant absorbance over the final hydrochloric acid concentration range of 0.02-0.07 M. Beer's law holds over the range of 0.1-0.9 μg/ml of gold (III) at 622 nm. The molar extinction coefficient of the complex is 1.1×105·l·mol-1·cm-1. The coefficient of variation was 1.34% for 0.5 μg/ml of gold (III). The coexistence of cations such as Pd (II), Fe (II), Ce (IV), and Mn (VII) interfered considerably with the determination.

  描述了用 5-对二甲基氨基肉桂基-1-苯基-2-硫代巴比妥酸 (DACTB) 测定金 (III) 的灵敏分光光度法。 DACTB 很容易与金 (III) 反应，在稀盐酸中形成蓝色络合物，可用氯仿萃取。相对于试剂空白，该络合物的氯仿溶液在 622 nm 处有最大吸收，并且在 0.02-0.07 M 的最终盐酸浓度范围内显示出恒定的吸光度。比尔定律在 0.1-0.9 μg/ml 金的范围内成立(III) 622 nm。该配合物的摩尔消光系数为1.1×105·l·mol-1·cm-1。 0.5 μg/ml 金 (III) 的变异系数为 1.34%。 Pd(II)、Fe(II)、Ce(IV)和Mn(VII)等阳离子的共存对测定有很大干扰。
• C-REL INHIBITORS AND USES THEREOF
  申请人：CORNELL UNIVERSITY

  公开号：US20150218109A1

  公开（公告）日：2015-08-06

  Compounds having a c-Rel inhibiting property according to the formula: (1) wherein R 1 and R 2 are each independently selected from hydrogen atom and hydrocarbon groups having at least one and up to thirty carbon atoms and optionally substituted with one or more heteroatoms selected from halogen, nitrogen, oxygen, and sulfur; R 3 is selected from hydrocarbon groups having at least one and up to thirty carbon atoms and optionally substituted with one or more heteroatoms selected from halogen, nitrogen, oxygen, and sulfur; and X 1 , X 2 , and X 3 are each independently selected from oxygen and sulfur atoms. Methods for treating diseases and conditions associated with c-Rel overexpression by administering compounds of Formula (1) or a pharmaceutical composition thereof to a subject afflicted with such a disease or condition are also described.

  具有抑制c-Rel性质的化合物按照公式（1）：其中R1和R2各自独立地选择氢原子和至少一个碳原子至三十个碳原子的含有一个或多个杂原子（选自卤素、氮、氧和硫）的烃基，并且可以被一个或多个杂原子（选自卤素、氮、氧和硫）取代；R3选择至少一个碳原子至三十个碳原子的含有一个或多个杂原子（选自卤素、氮、氧和硫）的烃基，并且可以被一个或多个杂原子（选自卤素、氮、氧和硫）取代；X1、X2和X3各自独立地选择氧原子和硫原子。还描述了通过向患有这种疾病或情况的受试者投与公式（1）的化合物或其制剂来治疗与c-Rel过度表达相关的疾病和情况的方法。
• Identification of Tri- and Tetracyclic Pyrimidinediones as Sirtuin Inhibitors
  作者：Dante Rotili、Domenico Tarantino、Vincenzo Carafa、Ester Lara、Sarah Meade、Giorgia Botta、Angela Nebbioso、Jörg Schemies、Manfred Jung、Aleksey G. Kazantsev、Manel Esteller、Mario F. Fraga、Lucia Altucci、Antonello Mai

  DOI：10.1002/cmdc.201000030

  日期：2010.5.3

  Sirtuins are deacetylase proteins that regulate transcription, genome maintenance, longevity, and metabolism. Eight compounds were identified as a novel class of sirtuin inhibitors, with 5, 7, and 9 being the most effective as SIRT1‐selective inhibitors. In U937 cells 5 induced apoptosis and displayed antiproliferative effects in Raji, DLD1, and HeLa cancer cells, suggesting potential utility in cancer

  Sirtuins是脱乙酰基酶蛋白，可调节转录，基因组维持，寿命和代谢。八种化合物被鉴定为一类新的瑟土因抑制剂，其中5种，7种和9种是最有效的SIRT1选择性抑制剂。在U937细胞中5诱导了Raji，DLD1和HeLa癌细胞的凋亡并显示出抗增殖作用，表明在癌症治疗中具有潜在的实用性。