4-chloro-2-phenyl-5,7-dihydrothieno<3,4-d>pyrimidine 6,6-dioxide | 174871-34-2

• 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: 4-chloro-2-phenyl-5,7-dihydrothieno<3,4-d>pyrimidine 6,6-dioxide
• 英文别名: 4-chloro-2-phenyl-5,7-dihydrothieno[3,4-d]pyrimidine 6,6-dioxide
• CAS: 174871-34-2
• 化学式: C₁₂H₉ClN₂O₂S
• 分子量: 280.735
• InChiKey: PANWEWRSTOVTIQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.23
• 重原子数：
  18.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  59.92
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  4-chloro-2-phenyl-5,7-dihydrothieno<3,4-d>pyrimidine 6,6-dioxide 在 水 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.5h， 生成 2-[4-(6,6-dioxo-2-phenyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)piperazin-1-yl]acetic acid
  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-氧四氢噻酚-3-羧酸甲酯 在 sodium methylate 、 间氯过氧苯甲酸 、 三氯氧磷 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 119.0h， 生成 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

文献信息

• Pyrimidine ortho-quinodimethanes
  作者：Augusto C. Tomé、José A.S. Cavaleiro、Richard C. Storr

  DOI：10.1016/0040-4020(95)01009-2

  日期：1996.1

  The pyrimidine sulfones 10, R = Me; Nu = OMe, NEt2, SPh, H and 11, R = Ph; Nu = OMe were synthesised from the dihydrothienopyrimidones 7, R = Me, Ph by conversion to the chloro derivatives 8 followed by oxidation with mCPBA and reaction with the appropriate nucleophile or hydrogen and Pd. Heating of the sulfones in 1,2,4-trichlorobenzene gave the pyrimidine o-quinodimethanes which were intercepted

  嘧啶砜10，R = Me; Nu = OMe，NEt 2，SPh，H和11，R = Ph；由二氢噻吩并嘧啶酮7（R = Me，Ph）转化为氯衍生物8，然后用mCPBA氧化并与适当的亲核试剂或氢和Pd反应，合成Nu = OMe 。在1,2,4-三氯苯中加热砜，得到嘧啶-邻-喹二甲烷，其在狄尔斯-阿尔德反应中截获，得到四氢喹唑啉。
• New pyrimidine and pyrimidone derivatives of [60]fullerence
  作者：Augusto C. Tomé、Roger F. Enes、João P.C. Tomé、João Rocha、Maria G.P.M.S. Neves、JoséA.S. Cavaleiro、José Elguero

  DOI：10.1016/s0040-4020(98)00652-8

  日期：1998.9

  Pyrimidine and pyrimidone derivatives of [60]fullerene have been obtained by Diels-Alder reaction of pyrimidine and pyrimidone o-quinodimethanes with C-60 Fullerene derivatives having hydrophobic or hydrophilic chains were prepared by acylation of one of the adducts. A porphyrin-C-60 hybrid was also prepared. (C) 1998 Elsevier Science Ltd. All rights reserved.