4-phenyl-pyrido[1,2-c]pyrimidine-1,3-dione | 109340-99-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: 4-phenyl-pyrido[1,2-c]pyrimidine-1,3-dione
• 英文别名: 4-Phenyl-pyrido[1,2-c]pyrimidin-1,3-dion；4-Phenylpyrido[1,2-c]pyrimidine-1,3-dione
• CAS: 109340-99-0
• 化学式: C₁₄H₁₀N₂O₂
• 分子量: 238.246
• InChiKey: ACZOFWCIASQNSP-UHFFFAOYSA-N

物化性质

• 熔点：
  229-231 °C(Solv: chloroform (67-66-3); methanol (67-56-1))
• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-phenyl-pyrido[1,2-c]pyrimidine-1,3-dione 在 potassium carbonate 、 potassium iodide 作用下， 以 丙酮 、 乙腈 为溶剂， 生成 4-phenyl-2-{4-[4-(quinolin-2-yl)piperazin-1-yl]butyl}-2H-pyrido[1,2-c]pyrimidine-1,3-dione
  参考文献：
  名称：

  Novel 4-aryl-pyrido[1,2-c]pyrimidines with dual SSRI and 5-HT1A activity. Part 5

  摘要：

  A series of novel 4-aryl-pyrido[1,2-c]pyrimidine derivatives containing a 1-(2-quinoline)piperazine moiety was synthesized. The chemical structure of new compounds was confirmed by FT-IR, H-1 NMR,C-13 NMR and HRMS spectra as well as elemental analysis. Affinity of the novel pyrido[1,2-c]pyrimidine derivatives for 5-HT1A, 5-HT2A receptors and serotonin transporter (SERT) was evaluated in an in vitro radioligand binding assay. Tested compounds showed moderate to high affinity for 5-HT1AR and SERT and low affinity for 5-HT2AR. Selected ligands were subjected to in vivo tests, such as induced hypothermia and the forced swimming test in mice, which determined presynaptic agonistic activity of the ligands 8d, 8e, 9d and 9e and presynaptic antagonistic activity of the ligands 8a, 8b, 9a, 9b. Additionally, metabolic stability evaluation was performed for selected ligands, proving that a para-substitution in the 4-aryl-pyrido[1,2-c]pyrimidine moiety leads to an increase in stability, whereas a substitution in the ortho-position lowers the stability. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.05.003
• 作为产物：
  描述：

  苯基吡啶-2-乙腈 在 硫酸 、 sodium ethanolate 作用下， 以 乙醇 、 溶剂黄146 为溶剂， 生成 4-phenyl-pyrido[1,2-c]pyrimidine-1,3-dione
  参考文献：
  名称：

  具有双重SSRI和5-HT 1A活性的新型4-芳基-吡啶并[1,2- c ]嘧啶。第4部分

  摘要：

  该项目描述了在两个系列-2H-吡啶并[新颖衍生物的合成，药理学和药效试验1，2 - c ^ ]嘧啶与潜在的二进制结合5-HT 1A受体和SSRI +血清素转运。 配体药效基团中存在的哌啶基-吲哚（8.1 – 8.7）和四氢吡啶基-吲哚（8.8 – 8.32）残基和吲哚5位取代基（R 3 = Br，Cl，F）对它们与两个分子的结合的影响目标进行了测试。 确认了哌啶基-吲哚残基对与两个靶标结合的显着影响，并且鉴定出具有高结合亲和力的化合物：K i 5-HT 1A  ＝ 12.4nM；m 5 HT 1A＝ 12.4nM。K i SERT = 15.6 nM 8.1 ; K i 5-HT 1A  = 5.6 nM; K i SERT = 20.7 nM 8.7，而四氢吡啶基-吲哚残基的存在会降低配体对5-HT 1A R的亲和力。氯（R 3）在该系列中的存在会导致结合力显着降低对两个目标（5-HT

  DOI：

  10.1016/j.ejmech.2014.10.069

文献信息

• Synthesis of new hexahydro- and octahydropyrido[1,2-c]pyrimidine derivatives with an arylpiperazine moiety as ligands for 5-HT1A and 5-HT2A receptors. Part 4
  作者：F HEROLD、M KROL、J KLEPS、G NOWAK

  DOI：10.1016/j.ejmech.2005.09.003

  日期：2006.1

  (6-18) were prepared and evaluated in vitro for their affinity for 5-HT1A, 5-HT2A, and alpha1 receptors. The influence of ortho substitution in the phenyl ring, substitution at position 4 of the pyrido[1,2-c]pyrimidine system, and its unsaturation degree were explored. The tested compounds showed high affinity for the 5-HT1A receptor (Ki = 1.3-79.2 nM) and moderate to low affinity for the 5-HT2A (Ki

  制备了芳基哌嗪（6-18）的新的4-芳基-2H-吡啶并[1,2-c]嘧啶-1,3-二酮衍生物，并对其在体外对5-HT1A，5-HT2A和α1的亲和力进行了评估。受体。探索了邻位取代在苯环，吡啶并[1,2-c]嘧啶体系第4位的取代及其不饱和度的影响。所测试的化合物显示出对5-HT1A受体的高亲和力（Ki = 1.3-79.2 nM），对5-HT2A（Ki = 51.7-1405 nM）和alpha1受体（Ki = 19.7-382.3 nM）具有中等至低亲和力。化合物8和10显示出最高的5-HT1A受体亲和力（分别为Ki = 1.3和2.2 nM），分别为37倍和35.9倍，相对于α1肾上腺素受体更具选择性。
• Synthesis and structure of novel 4-arylhexahydro-1<i>H</i>,3<i>H</i>-pyrido[1,2-<i>c</i>]pyrimidine derivatives
  作者：Franciszek Herold、Ewa Helbin、Marek Król、Irena Wolska、Jerzy Kleps

  DOI：10.1002/jhet.5570360210

  日期：1999.3

  A series of new 4-aryl-hexahydro-1H,3H-pyrido[1,2-c]pyrirnidine-1,3-dione derivatives 4a-k were prepared by catalytic hydrogenation of 4-aryl-1H,2H-pyrido[1,2-c]pyrirnidine-1,3-diones 3a-k. The structures of compounds were determined by 1H and 13C nmr spectroscopy in solution. Steric hindrance caused twisting of the phenyl ring with respect to the pyridopyrimidine system, the effect was confirmed by

  通过对4-芳基-1 H，2 H进行催化加氢制备了一系列新的4-芳基-六氢-1 H，3 H-吡啶并[1,2 - c ]吡啶-1,3-二酮衍生物4a-k。 -吡啶并[1,2 - c ]吡啶-1,3-二酮3a-k。通过溶液中的1 H和13 C nmr光谱确定化合物的结构。立体位阻引起苯环相对于嘧啶嘧啶体系的扭曲，该效果通过X射线衍射证实。
• Novel 4-aryl-pyrido[1,2-c]pyrimidines with dual SSRI and 5-HT1A activity: Part 2☆
  作者：Franciszek Herold、Łukasz Izbicki、Andrzej Chodkowski、Maciej Dawidowski、Marek Król、Jerzy Kleps、Jadwiga Turło、Irena Wolska、Gabriel Nowak、Katarzyna Stachowicz

  DOI：10.1016/j.ejmech.2009.07.007

  日期：2009.11

  showed that the presence of the 3-(4-piperidyl)-1H-indole group or its 5-methoxy derivative, as well as a para substitution with –OCH3 or –F in the aryl ring of 4-aryl-5,6,7,8-tetrahydro-pyrido[1,2-c]pyrimidine, results in an increased affinity for both the 5-HT1A receptors and SERT. In contrast, the presence of the 2-methyl-3-(4-piperidyl)-1H-indole group resulted in a considerable decrease in binding

  合成了4-芳基-5,6,7,8-四氢吡啶并[1,2- c ]嘧啶的衍生物。这些化合物含有3-（4-哌啶基）-1H-吲哚残基或其5-甲氧基或2-甲基衍生物。进行了体外结合试验，以确定化合物对大鼠大脑皮层中5-HT 1A受体和血清素转运蛋白（SERT）的亲和力。进行了体内研究，特别是诱导性低温测试和强迫游泳测试，以确定突触前和突触后5-HT 1A受体的激动/拮抗活性。使用分子建模技术确定所选化合物在5-HT 1A的结合模式受体和SERT。特区分析表明，3-（4-哌啶基）的存在-1 ħ -吲哚基或它的5-甲氧基衍生物，以及一对位取代有-OCH 3或-F 4 -芳基的芳基环-5,6,7,8-四氢-吡啶并[1,2- c ]嘧啶对5-HT 1A受体和SERT的亲和力均增加。相反，2-甲基-3-（4-哌啶基）-1 H-吲哚基的存在导致结合亲和力显着降低。
• Novel 4-aryl-pyrido[1,2-c]pyrimidines with dual SSRI and 5-HT1A activity. Part 4
  作者：Andrzej Chodkowski、Martyna Z. Wróbel、Jadwiga Turło、Jerzy Kleps、Agata Siwek、Gabriel Nowak、Mariusz Belka、Tomasz Bączek、Aleksander P. Mazurek、Franciszek Herold

  DOI：10.1016/j.ejmech.2014.10.069

  日期：2015.1

  This project describes the synthesis, pharmacological and pharmacodynamic tests on two series of novel derivatives of 2H-pyrido[1,2-c]pyrimidine with potential binary binding to 5-HT1A receptors and SSRI + serotonin transporters. The influence of piperidinyl-indole (8.1–8.7) and tetrahydropyridinyl-indole (8.8–8.32) residues and indole 5-position substituents (R3 = Br, Cl, F) present in the pharmacophore

  该项目描述了在两个系列-2H-吡啶并[新颖衍生物的合成，药理学和药效试验1，2 - c ^ ]嘧啶与潜在的二进制结合5-HT 1A受体和SSRI +血清素转运。 配体药效基团中存在的哌啶基-吲哚（8.1 – 8.7）和四氢吡啶基-吲哚（8.8 – 8.32）残基和吲哚5位取代基（R 3 = Br，Cl，F）对它们与两个分子的结合的影响目标进行了测试。 确认了哌啶基-吲哚残基对与两个靶标结合的显着影响，并且鉴定出具有高结合亲和力的化合物：K i 5-HT 1A  ＝ 12.4nM；m 5 HT 1A＝ 12.4nM。K i SERT = 15.6 nM 8.1 ; K i 5-HT 1A  = 5.6 nM; K i SERT = 20.7 nM 8.7，而四氢吡啶基-吲哚残基的存在会降低配体对5-HT 1A R的亲和力。氯（R 3）在该系列中的存在会导致结合力显着降低对两个目标（5-HT
• Synthesis of novel pyrido[1,2-c]pyrimidine derivatives with rigidized tryptamine moiety as potential SSRI and 5-HT1A receptor ligands
  作者：Grzegorz Ślifirski、Marek Król、Jerzy Kleps、Szymon Ulenberg、Mariusz Belka、Tomasz Bączek、Agata Siwek、Katarzyna Stachowicz、Bernadeta Szewczyk、Gabriel Nowak、Andrzej Bojarski、Anna E. Kozioł、Jadwiga Turło、Franciszek Herold

  DOI：10.1016/j.ejmech.2019.01.031

  日期：2019.3

  of new derivatives of 4-aryl-pyrido[1,2-c]pyrimidine 9.1–9.27 having conformationally restricted tryptamine moiety. In vitro studies (RBA) have shown that derivatives 9.1, 9.2, 9.4, 9.7, 9.9, 9.14 and 9.27 exhibit high affinity to molecular targets 5-HT1A receptor and SERT protein. In general, compounds with an unsubstituted or a para-substituted benzene ring of the pyrido[1,2-c]pyrimidine residue

  该研究启用获得号码4芳基-吡啶并[1,2-c]嘧啶的新衍生物的9.1 - 9.27具有构象限制的色胺部分。体外研究（RBA）已经表明衍生物9.1，9.2，9.4，9.7，9.9，9.14和9.27显示出高亲和力的分子靶点5-HT 1A受体和SERT蛋白。通常，在末端部分具有吡啶并[1,2-c]嘧啶残基的未取代或对位取代的苯环的化合物的特征在于更高的结合能力，这可以通过更大的结构灵活性来证明。对于选定的化合物9.1，9.7，9.9和9.27，进一步在体外，体内和代谢稳定性试验进行。在体外在扩展受体分布研究（d 2，5-HT 2A，5-HT 6和5-HT 7）表明他们对选择性的5-HT 1A受体和SERT蛋白。的体内研究（在小鼠中8-OH-DPAT诱导的低温，FST），发现该化合物9.1具有5-HT的突触前受体激动剂的性质1A受体和化合物9.7展示了5的突触前拮抗剂的性质-HT 1A受体。代谢