[(5E)-5-(3-[4-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl)-1,4-diazepan-1-yl]propylidene)-10,11-dihydro-5H-dibenzo[a,d][7]annulen-3-yl]acetic acid | 943782-38-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 二苯并环庚烯
• 英文名称: [(5E)-5-(3-[4-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl)-1,4-diazepan-1-yl]propylidene)-10,11-dihydro-5H-dibenzo[a,d][7]annulen-3-yl]acetic acid
• 英文别名: 2-[(2E)-2-[3-[4-(1,3-dimethyl-2,6-dioxopyrimidin-4-yl)-1,4-diazepan-1-yl]propylidene]-5-tricyclo[9.4.0.03,8]pentadeca-1(15),3(8),4,6,11,13-hexaenyl]acetic acid
• CAS: 943782-38-5
• 化学式: C₃₁H₃₆N₄O₄
• 分子量: 528.651
• InChiKey: QUPFMAXRMLKPQC-JQAMDZJQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  39
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  84.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-甲基高哌嗪 在 硫酸 、 sodium hydride 、 potassium carbonate 、 溶剂黄146 、 三乙胺 、 N,N-二异丙基乙胺 、 potassium iodide 、 sodium hydroxide 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 异丙醇 、 甲苯 、 mineral oil 为溶剂， 反应 42.67h， 生成 [(5Z)-5-(3-[4-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl)-1,4-diazepan-1-yl]propylidene)-10,11-dihydro-5H-dibenzo[a,d][7]annulen-3-yl]acetic acid 、 [(5E)-5-(3-[4-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl)-1,4-diazepan-1-yl]propylidene)-10,11-dihydro-5H-dibenzo[a,d][7]annulen-3-yl]acetic 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 relationship of tricyclic carboxylic acids as novel anti-histamines
  作者：Katsumi Kubota、Hirotaka Kurebayashi、Hirotaka Miyachi、Masanori Tobe、Masako Onishi、Yoshiaki Isobe

  DOI：10.1016/j.bmc.2011.03.003

  日期：2011.5

  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.