Diethyl N-(1,3-Dimethyl-2,4-dioxo-6-pyrimidinyl)aminomethylenemalonate | 104312-63-2

• 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: Diethyl N-(1,3-Dimethyl-2,4-dioxo-6-pyrimidinyl)aminomethylenemalonate
• 英文别名: Diethyl 2-[[(1,3-dimethyl-2,6-dioxopyrimidin-4-yl)amino]methylidene]propanedioate
• CAS: 104312-63-2
• 化学式: C₁₄H₁₉N₃O₆
• 分子量: 325.321
• InChiKey: CDLQREUILGNBIV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  23
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Diethyl N-(1,3-Dimethyl-2,4-dioxo-6-pyrimidinyl)aminomethylenemalonate 以 二苯醚 为溶剂， 反应 1.0h， 以89%的产率得到5-Hydroxy-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester
  参考文献：
  名称：

  吡啶并[2,3- d ]嘧啶的区域选择性合成

  摘要：

  乙氧基亚甲基丙二酸二乙酯（1）和6-氨基-1,3-二甲基尿嘧啶（2）的反应被确定为区域选择性的。在酸性条件下，产物是先前分离的7-氧代吡啶并[2,3- d ]嘧啶（3），而在存在一当量碱然后热环化的情况下，异构体5-氧代吡啶并[2,3- d ]形成嘧啶（5）。

  DOI：

  10.1002/jhet.5570220569
• 作为产物：
  描述：

  1,3-二甲基-6-氨基脲嘧啶 、 乙氧基甲叉丙二酸二乙酯 在 sodium ethanolate 作用下， 以 乙醇 为溶剂， 以99%的产率得到Diethyl N-(1,3-Dimethyl-2,4-dioxo-6-pyrimidinyl)aminomethylenemalonate
  参考文献：
  名称：

  吡啶并[2,3- d ]嘧啶的区域选择性合成

  摘要：

  乙氧基亚甲基丙二酸二乙酯（1）和6-氨基-1,3-二甲基尿嘧啶（2）的反应被确定为区域选择性的。在酸性条件下，产物是先前分离的7-氧代吡啶并[2,3- d ]嘧啶（3），而在存在一当量碱然后热环化的情况下，异构体5-氧代吡啶并[2,3- d ]形成嘧啶（5）。

  DOI：

  10.1002/jhet.5570220569

文献信息

• Regioselective synthesis of pyrido[2,3-<i>d</i>]pyrimidines
  作者：Gary L. Anderson

  DOI：10.1002/jhet.5570220569

  日期：1985.9

  ethoxymethylenemalonate (1) and 6-amino-1,3-dimethyluracil (2) was determined to be regioselective. Under acidic conditions the product was the previously isolated 7-oxopyrido[2,3-d]pyrimidine (3), while in the presence of one equivalent of base followed by thermal cyclization, the isomeric 5-oxopyrido[2,3-d]pyrimidine (5) is formed.

  乙氧基亚甲基丙二酸二乙酯（1）和6-氨基-1,3-二甲基尿嘧啶（2）的反应被确定为区域选择性的。在酸性条件下，产物是先前分离的7-氧代吡啶并[2,3- d ]嘧啶（3），而在存在一当量碱然后热环化的情况下，异构体5-氧代吡啶并[2,3- d ]形成嘧啶（5）。
• ANDERSON, G. L., J. HETEROCYCL. CHEM., 1985, 22, N 5, 1469-1470
  作者：ANDERSON, G. L.

  DOI：——

  日期：——
• Synthesis and pharmacology of pyrido[2,3-d]pyrimidinediones bearing polar substituents as adenosine receptor antagonists
  作者：Jacek Bulicz、Daniela C.G. Bertarelli、Dieter Baumert、Friederike Fülle、Christa E. Müller、Dieter Heber

  DOI：10.1016/j.bmc.2005.12.008

  日期：2006.4

  Amino-substituted pyrido[2,3-d]pyrimidinediones have previously been found to bind to adenosine A(1) and A(2A) receptors in micromolar concentrations. The present study was aimed at studying the structure-activity relationships of this class of compounds in more detail. Most of the investigated compounds were provided with polar substituents. such as ethoxycarbonyl groups and basic amino functions, in order to improve their water-solubility. The compounds were synthesized starting from 6-amino-1,3-dimethyfuracil via different reaction sequences involving (cyano)acetylation, Vilsmeier formylation, or reaction with diethyl ethoxymethylemalonate (EMME). The most potent and selective compound of the present series was 6-carbethoxy-1,2,3,4-tetrahydro-1.3-dimethyl-5-(2-naphthylmethyl) aminopyrido[2,3-d]pyrimidine-2,4-dione (11c) with a K-i value of 5 nM at rat and 25 nM at human A, receptors. The compound was more than 60-fold selective versus A(3) and more than 300-fold selective versus A2A receptors. It showed all over 300-fold improvement with respect to the lead compound. In GTP gamma S binding studies at membranes of Chinese hamster ovary cells recombinantly expressing the human adenosine A, receptor, 11c behaved as an antagonist with inverse agonistic activity. A regioisomer of 11c, 6-carbethoxy-1,2,3,4-tetrahydro-1,3-dimethyl-7-(2-naphthylmethyl)aminopyrido[2,3-d]pyrimidine-2,4-dione (7a) in which the 2-naphthylmethylamino substituent at position 5 of 11c was moved to the 7-position, was a relatively potent (K-i = 226 nM) and selective (> 20-fold) A(3) ligand. In the series of compounds lacking an electron-withdrawing ethoxycarbonyl or cyano substituent in the 6-position, compounds with high affinity for adenosine A(2A) receptors were identified. Such as 1,2,3,4-tetrahydro-1,3-dimethyl-5-(1-naphthyl)aminopyrido[2,3-d]pyrimidine-2,4-dioile 16b (K-i human A(2A) = 81.3 nM, K-i human A(1) = 153 nM, and K-i human A(3) > 10,000 nM). (c) 2006 Elsevier Ltd. All rights reserved.