4-((1-(4-((3,4-dimethoxyphenyl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidin-3-yl)aminoformyl)benzoic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-((1-(4-((3,4-dimethoxyphenyl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidin-3-yl)aminoformyl)benzoic acid
• 英文别名: 4-((1-(4-((3,4-dimethoxyphenyl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidin-3-yl)carbamoyl)benzoic acid；4-[[1-[4-(3,4-dimethoxyanilino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl]pyrrolidin-3-yl]carbamoyl]benzoic acid
• 化学式: C₂₇H₂₉N₅O₅
• 分子量: 503.558
• InChiKey: AQPWGHPLHYLGRK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  126
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2,4-二氯-5,6-三甲基嘧啶 在 palladium 10% on activated carbon 、 氢气 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N-甲基吡咯烷酮 、 甲醇 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 4-((1-(4-((3,4-dimethoxyphenyl)amino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidin-3-yl)aminoformyl)benzoic acid
  参考文献：
  名称：

  Discovery of novel Syk/PDGFR-α/c-Kit inhibitors as multi-targeting drugs to treat rheumatoid arthritis

  摘要：

  Due to the complex biological pathways involved in rheumatoid arthritis, discovery of multi-targeting small molecules provides an effective strategy to achieve better efficacy and lower toxicity. Herein the first Syk/PDGFR-alpha/c-Kit inhibitors were designed and evaluated. Dihydrofuropyrimidine derivative 13 showed potent inhibitory activity against the three targets. Importantly, compound 13 exhibited good cellular efficacy against fibroblast-like synoviocytes (IC50 = 3.21 mu M) and mouse bone marrow-derived mast cells (IC50 = 2.03 mu M) and significantly decreased the secretion of inflammatory cytokines. Thus, Syk/PDGFR-alpha/c-Kit triple inhibitor 13 represented a promising lead compound for the treatment of RA.

  DOI：

  10.1016/j.bmc.2018.06.029

文献信息

• 嘧啶并饱和脂肪环二胺类化合物及其用途
  申请人：华东理工大学

  公开号：CN105732590B

  公开（公告）日：2018-07-24

  本发明的发明人设计、并合成了一种具有全新结构的嘧啶并饱和脂肪环二胺类化合物。经测试表明：本发明公开的嘧啶并饱和脂肪环二胺类化合物中大部分化合物对脾酪氨酸激酶(Syk)，干细胞受体c‑Kit和血小板衍生生长因子受体(PDGFR‑α)这三个靶点有良好的抑制活性。部分化合物在炎症相关的滑膜细胞和肥大细胞增殖活性抑制实验中，表现出较好的抑制活性，并且能有效地抑制相应细胞中炎症相关因子IL‑6、MMP‑3和TNF‑α的分泌，显示出较好的抗类风湿性关节炎(RA)药效。本发明为今后进一步设计开发新型抗类风湿性关节炎药物奠定了结构基础。
• Discovery of novel Syk/PDGFR-α/c-Kit inhibitors as multi-targeting drugs to treat rheumatoid arthritis
  作者：Xiaokang Li、Yahui Huang、Junfei Cheng、Lingling Zhang、Fei Mao、Jin Zhu、Chunquan Sheng、Jian Li

  DOI：10.1016/j.bmc.2018.06.029

  日期：2018.8

  Due to the complex biological pathways involved in rheumatoid arthritis, discovery of multi-targeting small molecules provides an effective strategy to achieve better efficacy and lower toxicity. Herein the first Syk/PDGFR-alpha/c-Kit inhibitors were designed and evaluated. Dihydrofuropyrimidine derivative 13 showed potent inhibitory activity against the three targets. Importantly, compound 13 exhibited good cellular efficacy against fibroblast-like synoviocytes (IC50 = 3.21 mu M) and mouse bone marrow-derived mast cells (IC50 = 2.03 mu M) and significantly decreased the secretion of inflammatory cytokines. Thus, Syk/PDGFR-alpha/c-Kit triple inhibitor 13 represented a promising lead compound for the treatment of RA.