5-hydroxy-1,3,8-trimethylpyrido[2,3-d]pyrimidine-2,4,7(1H,3H,8H)-trione | 93738-66-0

• 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: 5-hydroxy-1,3,8-trimethylpyrido[2,3-d]pyrimidine-2,4,7(1H,3H,8H)-trione
• 英文别名: 5-Hydroxy-1,3,8-trimethylpyrido[2,3-d]pyrimidine-2,4,7-trione
• CAS: 93738-66-0
• 化学式: C₁₀H₁₁N₃O₄
• 分子量: 237.215
• InChiKey: ZTEWURHNRLGQKN-UHFFFAOYSA-N

物化性质

• 沸点：
  331.7±52.0 °C(Predicted)
• 密度：
  1.56±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  81.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-hydroxy-1,3,8-trimethylpyrido[2,3-d]pyrimidine-2,4,7(1H,3H,8H)-trione 在 sodium hydroxide 、 三乙胺 、 三氯氧磷 作用下， 以 异丙醇 、 乙腈 为溶剂， 反应 25.0h， 生成 4,6,8-Trimethyl-4,6,8,18-tetrazatetracyclo[8.8.0.02,7.012,17]octadeca-1(18),2(7),10,12,14,16-hexaene-3,5,9-trione
  参考文献：
  名称：

  Ring closure reaction of 5-hydroxy-pyrido[2,3-d]pyrimidine-2,4,7-triones to benzo[b]pyrimido[4,5-h]1,6-naphthyridine-1,3,6-triones

  摘要：

  N-Substituted aminouracils (1) react with malonates by cyclocondensation to 5-hydroxy-pyrido [2,3-d] pyrimidine-2,4,7-triones (2), which give with triethylorthoformate and aniline 6-(phenylaminomethylene)-pyrido[2,3-d]pyrimidine-tetraone (3). Halogenation of 2a-d (with R(2) = Me) with phosphorylchloride leads to 5,7-dichloro-pyrido [2,3-d]pyrimidine-2,4-diones (4) by cleavage of the methyl group at N-8, whereas Vilsmeier reaction of 2 affords 5-chloro-6-formyl derivatives (6), which cyclize with arylamines to give benzo[b]pyrimido[4,5-h] 1,6-naphthyridines (9). Compounds 9 were obtained independently by amination of the tosylates 5 to the 5-arylamino compounds 8, and Vilsmeier formylation to yield 9.

  DOI：

  10.1002/prac.19963380129
• 作为产物：
  描述：

  6-氯-1,3-二甲基脲嘧啶 在 三乙胺 作用下， 以 二苯醚 、 乙醇 、 水 为溶剂， 反应 0.67h， 生成 5-hydroxy-1,3,8-trimethylpyrido[2,3-d]pyrimidine-2,4,7(1H,3H,8H)-trione
  参考文献：
  名称：

  5-取代氨基-3-甲基吡啶并[2,3-d]嘧啶类化合物及其制备与应用

  摘要：

  本发明的5‑取代氨基‑3‑甲基吡啶并[2,3‑d]嘧啶类化合物及其制备与应用，属于医药技术领域。化合物具体为5‑取代氨基‑3‑甲基吡啶并[2,3‑d]嘧啶‑2,4,7(1H,3H,8H)‑三酮类化合物，其结构通式如式(I)所示：R1为氢、甲基或乙基；R2为氢、甲基、苄基、2‑甲基苄基；R3为异丙基、环丙基、二甲氨基乙基、3‑吗啉丙基、3‑三氟甲基苯基、4‑三氟甲基苯基、4‑三氟甲氧基苯基、3‑氯‑4‑氟苯基、3‑氯‑4‑三氟甲基苯基、吡啶‑2‑基、4‑甲基吡啶‑2‑基、2‑(甲氧羰基)苯基、3‑羧基苯基、2‑氧代‑2‑(对甲苯氨基)乙基、2‑氧代‑2‑(邻甲苯氨基)乙基或3‑[(3‑吗啉丙基)氨甲酰]苯基。本发明化合物的合成方法简便，适于工业化生产，生物活性测试显示此类化合物具有抗肿瘤活性，可应用于抗肿瘤药物中。

  公开号：

  CN114456166B

文献信息

• Synthesis of 5-mono- and 5,7-diamino-pyrido[2,3-<i>d</i>]-pyrimidinediones with potential biological activity by regioselective amination
  作者：Dang Van Tinh、Wolfgang Stadlbauer

  DOI：10.1002/jhet.5570450329

  日期：2008.5

  triphenyl-phosphane via Staudinger reaction. Hydrolysis with aqueous acetic acid produced in one step 7-unsubstituted-amino-pyrido[2,3-d]pyrimidine-2,4-diones 12. In a similar amination reaction, 5-chloropyrido[2,3-d]pyrimidine-2,4,7-triones 13 were aminated and formylated to 5-alkyl/arylamino-6-formyl derivatives 14-16 in a combined one-step-reaction with bulky arylamines or alkylamines in the presence of dimethylformamide

  由相应的5,7-二氯制备5-烷基-/芳基氨基-和5,7-二烷基/芳基氨基-吡啶并[2,3- d ]嘧啶-2,4-二酮（4,5,7-9）。在区域选择性反应中与脂肪族和芳香族胺3和6一起合成-pyrido [2,3- d ] pyrimidine-2,4-diones 2。通过5-氨基-7-氯衍生物4的叠氮化而获得的7-单叠氮化物10通过Staudinger反应与三苯基膦反应而转化为亚氨基正膦。用一步法制得的乙酸水溶液水解7-未取代的氨基-吡啶并[2,3 - d ]嘧啶-2,4-二酮12。以类似的胺化反应中，5-氯吡啶并[2,3- d ]嘧啶-2,4,7-三酮13进行胺化和甲酰化，5-烷基/芳基氨基-6-甲酰基衍生物14 - 16在组合的单步-在二甲基甲酰胺的存在下与庞大的芳胺或烷基胺的反应。
• Ring closure reactions of 5-azidopyrido[2,3-<i>d</i>]pyrimidinetriones to isoxazolo- and oxadiazolopyrido[2,3-<i>d</i>]pyrimidinetriones
  作者：Dang Van Tinh、Wolfgang Stadlbauer

  DOI：10.1002/jhet.5570450621

  日期：2008.11

  Thermal decomposition of 5-azidopyrido[2,3-d]pyrimidines 2 and 7 having reactive ortho-substituents such as a formyl or a nitro group yielded isoxazolo[3′,4′:4,5]pyrido[2,3-d]pyrimidines 3 or oxadiazolo-[3′,4′:4,5]pyrido[2,3-d]pyrimidines 9. The reaction conditions of the azide decomposition were studied by differential scanning calorimetry (DSC). In addition, desoxygenation of N-oxides 9 to oxadiazoles

  具有反应性邻位取代基（如甲酰基或硝基）的5-叠氮基吡啶并[2,3 - d ]嘧啶2和7的热分解生成异恶唑并[3'，4'：4,5]吡啶并[2,3- d ]嘧啶3或恶二唑-[3'，4'：4,5]吡啶[2,3- d ]嘧啶9.通过差示扫描量热法（DSC）研究了叠氮化物分解的反应条件。另外，研究了将N-氧化物9脱氧为恶二唑10和将叠氮化物7区域选择性还原为胺8。
• Ring closure reactions of pyrido[2,3-<i>d</i>]pyrimidines to pyrano[2′,3′:4,5]- and oxazolo[5′,4′:4,5]pyrido[2,3-<i>d</i>]pyrimidines
  作者：Dang Van Tinh、Wolfgang Stadlbauer

  DOI：10.1002/jhet.5570450517

  日期：2008.9

  zinc in the presence of carboxylic acids/anhydrides gave 2-alkyloxazolo[5′,4′:4,5]pyrido[2,3-d]pyrimidines 4, which were ring-opened to 6-aminopyrido[2,3-d]pyrimidines 5, 6 and 7. Cyclization of 6-aminopyrido[2,3-d]pyrimidines 6 with benzoylchlorides 8 gave 2-aryloxazolo[5′,4′:4,5]pyrido[2,3-d]pyrimidines 9. Reaction conditions for the cyclization have been studied by differential scanning calorimetry

  5-羟基-吡啶并[2,3- d ]嘧啶1与丙二酸酯的环缩合反应得到吡喃并[2'，3'：4,5]-吡啶并[2,3- d ]嘧啶2。硝化1并在羧酸/酸酐存在下用锌还原得到2-烷基恶唑并[5'，4'：4,5]吡啶[2,3- d ]嘧啶4，将其开环成6-氨基吡啶[2，3- d ]嘧啶5、6和7。6-氨基吡啶并[2,3- d ]嘧啶6与苯甲酰氯8的环化反应生成2-芳基恶唑并[5'，4'：4,5]吡啶并[2,3- d ]嘧啶9。通过差示扫描量热法（DSC）已经研究了用于环化的反应条件。
• Pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione derivatives as RAF-MEK-ERK pathway signaling pathway blockers: Synthesis, cytotoxic activity, mechanistic investigation and structure-activity relationships
  作者：Qian Xie、Yanni Shen、Yanli Meng、Jianhui Liang、Jing Xu、Shishao Liang、Xiaoping Liu、Yan Wang、Chun Hu

  DOI：10.1016/j.ejmech.2022.114579

  日期：2022.10

  often appears to re-enhance ERK1/2 signaling. Here we report the design, synthesis, biological activity of a series of novel pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione derivatives based on compound 1. Among them, the target compound N-(3-chlorophenyl)-2-((1,3-dimethyl-7-(4-methylpiperazin-1-yl)-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-5-yl)amino)acetamide (14m) exhibited excellent antiproliferative

  ERK1/2（RAF-MEK-ERK）信号通路的组成型激活已在多种肿瘤中广泛观察到，并且已证明阻断ERK1/2信号通路可减少肿瘤生长。因此，ERK1/2信号通路已成为癌症治疗的一个有趣的治疗靶点。尽管 BRAF 和 MEK 抑制剂在临床治疗中取得了成功，但耐药性通常会重新增强 ERK1/2 信号传导。在这里，我们报告了一系列基于化合物1的新型吡啶并[2,3- d ]嘧啶-2,4(1 H ,3 H )-二酮衍生物的设计、合成和生物活性。其中，目标化合物N-(3-氯苯基)-2-((1,3-二甲基-7-(4-甲基哌嗪-1-基)-2,4-二氧代-1,2,3,4-四氢吡啶并[2,3- d ]pyrimidin-5-yl)amino)acetamide ( 14m ) 对 MCF-7、A375、SK-MEL-2 和 SK-HEP-1 细胞表现出优异的抗增殖活性，在 C28/I2 细胞中具有低细胞毒性。肿瘤球体测定显示14m在抑制
• Ring closure reaction of 5-hydroxy-pyrido[2,3-d]pyrimidine-2,4,7-triones to benzo[b]pyrimido[4,5-h]1,6-naphthyridine-1,3,6-triones
  作者：Ahmed F. A. Khattab、Dang Van Tinh、Wolfgang Stadlbauer

  DOI：10.1002/prac.19963380129

  日期：——

  N-Substituted aminouracils (1) react with malonates by cyclocondensation to 5-hydroxy-pyrido [2,3-d] pyrimidine-2,4,7-triones (2), which give with triethylorthoformate and aniline 6-(phenylaminomethylene)-pyrido[2,3-d]pyrimidine-tetraone (3). Halogenation of 2a-d (with R(2) = Me) with phosphorylchloride leads to 5,7-dichloro-pyrido [2,3-d]pyrimidine-2,4-diones (4) by cleavage of the methyl group at N-8, whereas Vilsmeier reaction of 2 affords 5-chloro-6-formyl derivatives (6), which cyclize with arylamines to give benzo[b]pyrimido[4,5-h] 1,6-naphthyridines (9). Compounds 9 were obtained independently by amination of the tosylates 5 to the 5-arylamino compounds 8, and Vilsmeier formylation to yield 9.