6-(1,4-Diazepan-1-yl)-1,3-dimethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione | 943782-97-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 6-(1,4-Diazepan-1-yl)-1,3-dimethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione
• 英文别名: 6-(1,4-diazepan-1-yl)-1,3-dimethylpyrimidine-2,4-dione
• CAS: 943782-97-6
• 化学式: C₁₁H₁₈N₄O₂
• 分子量: 238.29
• InChiKey: KSBIEHXPJNFNSR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  55.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-(1,4-Diazepan-1-yl)-1,3-dimethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione 、 Methyl 11-(3-bromopropyl)-5,6-dihydrobenzo[b][1]benzazepine-2-carboxylate 在 N,N-二异丙基乙胺 、 potassium iodide 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 6.0h， 生成 5-(3-(4-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl)-1,4-diazepan-1-yl)propyl)-10,11-dihydro-5H-dibenzo[b,f]azepine-3-carboxylic acid
  参考文献：
  名称：

  Synthesis and structure–activity relationship of tricyclic carboxylic acids as novel anti-histamines

  摘要：

  A series of tricyclic carboxylic acids having 6-amino-pyrimidine-2,4(1H,3H)-dione with piperazino or homopiperazino moiety linked by propylene, were synthesized and evaluated for their affinity toward human histamine H(1) receptor and Caco-2 cell permeability. Selected compounds were further evaluated for their oral anti-histaminic activity in mice, bioavailability in rats, and their anti-inflammatory activity in mice OVA-induced biphasic cutaneous reaction model. Among the compounds tested, dibenzoxazepine carboxylic acid 13b showed both histamine H(1) receptor antagonistic activity and anti-inflammatory activity in vivo. In addition, 13b exhibited low affinity toward alpha(1) receptor and low occupancy of H(1) receptor in the brain. It is therefore, believed that 13b is a potential candidate for development as 3rd generation anti-histamine. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.03.003

文献信息

• Synthesis and structure–activity relationships of phenothiazine carboxylic acids having pyrimidine-dione as novel histamine H1 antagonists
  作者：Katsumi Kubota、Hirotaka Kurebayashi、Hirotaka Miyachi、Masanori Tobe、Masako Onishi、Yoshiaki Isobe

  DOI：10.1016/j.bmcl.2009.03.124

  日期：2009.5

  A series of phenothiazine carboxylic acid derivatives, having 6-amino-pyrimidine-2,4(1H,3H)-dione moiety via a appropriate linker, were synthesized and evaluated for their affinity toward human histamine H1 receptor and Caco-2 cell permeability. Selected compounds were further evaluated for their oral anti-histaminic activity in mice and bioavailability in rats. Finally, promising compounds were examined

  合成了一系列通过适当的接头具有6-氨基-嘧啶-2,4（1 H，3 H）-二酮部分的吩噻嗪羧酸衍生物，并评估了它们对人组胺H 1受体和Caco-2的亲和力细胞通透性。进一步评估了所选化合物在小鼠中的口服抗组胺活性和在大鼠中的生物利用度。最后，在小鼠OVA诱导的双相皮肤反应模型中检查了有希望的化合物的抗炎潜力。在所测试的化合物中，吩噻嗪乙酸化合物27在体内模型中均显示出组胺H 1受体拮抗活性和抗炎活性。