ethyl 2-[4-[(6,6-dioxo-2-phenyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)amino]phenyl]acetate | 1436866-20-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: ethyl 2-[4-[(6,6-dioxo-2-phenyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)amino]phenyl]acetate
• CAS: 1436866-20-4
• 化学式: C₂₂H₂₁N₃O₄S
• 分子量: 423.492
• InChiKey: CHXCENRXRIKNJL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.42
• 重原子数：
  30.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  98.25
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  ethyl 2-[4-[(6,6-dioxo-2-phenyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)amino]phenyl]acetate 在 水 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 1.5h， 以44%的产率得到4-chloro-2-phenyl-5,7-dihydrothieno<3,4-d>pyrimidine 6,6-dioxide
  参考文献：
  名称：

  Identification of the fused bicyclic 4-amino-2-phenylpyrimidine derivatives as novel and potent PDE4 inhibitors

  摘要：

  2-Phenyl-4-piperidinyl-6,7-dihydrothieno[3,4-d] pyrimidine derivative (2) was found to be a new PDE4 inhibitor with moderate PDE4B activity (IC50 = 150 nM). A number of derivatives with a variety of 4-amino substituents and fused bicyclic pyrimidines were synthesized. Among these, 5,5-dioxo-7,8-dihydro-6H-thiopyrano[3,2-d] pyrimidine derivative (18) showed potent PDE4B inhibitory activity (IC50 = 25 nM). Finally, N-propylacetamide derivative (31b) was determined as a potent inhibitor for both PDE4B (IC50 = 7.5 nM) and TNF-alpha production in mouse splenocytes (IC50 = 9.8 nM) and showed good in vivo anti-inflammatory activity in the LPS-induced lung inflammation model in mice (ID50 = 18 mg/kg). The binding mode of the new inhibitor (31e) in the catalytic site of PDE4B is presented based on an X-ray crystal structure of the ligand-enzyme complex. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.104
• 作为产物：
  描述：

  4-氨基苯乙酸乙酯 、 4-chloro-2-phenyl-5,7-dihydrothieno<3,4-d>pyrimidine 6,6-dioxide 以 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 ethyl 2-[4-[(6,6-dioxo-2-phenyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)amino]phenyl]acetate
  参考文献：
  名称：

  Identification of the fused bicyclic 4-amino-2-phenylpyrimidine derivatives as novel and potent PDE4 inhibitors

  摘要：

  2-Phenyl-4-piperidinyl-6,7-dihydrothieno[3,4-d] pyrimidine derivative (2) was found to be a new PDE4 inhibitor with moderate PDE4B activity (IC50 = 150 nM). A number of derivatives with a variety of 4-amino substituents and fused bicyclic pyrimidines were synthesized. Among these, 5,5-dioxo-7,8-dihydro-6H-thiopyrano[3,2-d] pyrimidine derivative (18) showed potent PDE4B inhibitory activity (IC50 = 25 nM). Finally, N-propylacetamide derivative (31b) was determined as a potent inhibitor for both PDE4B (IC50 = 7.5 nM) and TNF-alpha production in mouse splenocytes (IC50 = 9.8 nM) and showed good in vivo anti-inflammatory activity in the LPS-induced lung inflammation model in mice (ID50 = 18 mg/kg). The binding mode of the new inhibitor (31e) in the catalytic site of PDE4B is presented based on an X-ray crystal structure of the ligand-enzyme complex. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.104