N-(3,5-difluorobenzyl)thiourea | 123566-61-0

• 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: N-(3,5-difluorobenzyl)thiourea
• 英文别名: (3,5-Difluoro-benzyl)-thiourea；(3,5-difluorophenyl)methylthiourea
• CAS: 123566-61-0
• 化学式: C₈H₈F₂N₂S
• 分子量: 202.228
• InChiKey: ZTCPCQFPXVGWPL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  70.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,1,3,3-四甲氧基丙烷 、 N-(3,5-difluorobenzyl)thiourea 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 0.42h， 生成 1-(3,5-difluorobenzyl)-1,2-dihydropyrimidine-2-thione
  参考文献：
  名称：

  Some benzyl-substituted imidazoles, triazoles, tetrazoles, pyridinethiones, and structural relatives as multisubstrate inhibitors of dopamine .beta.-hydroxylase. 4. Structure-activity relationships at the copper binding site

  摘要：

  Structure-activity relationships (SAR) were determined for novel multisubstrate inhibitors of dopamine beta-hydroxylase (DBH; EC 1.14.17.1) by examining the effects upon in vitro inhibitory potencies resulting from structural changes at the copper-binding region of inhibitor. Attempts were made to determine replacement groups for the thione sulfur atom of the prototypical inhibitor 1-(4-hydroxybenzyl)imidazole-2-thione described previously. The synthesis and evaluation of oxygen and nitrogen analogues of the soft thione group demonstrated the sulfur atom to be necessary for optimal activity. An additional series of imidazole-2-thione relatives was prepared in an effort to probe the relationship between the pKa of the ligand group and inhibitory potency. In vitro inhibitory potency was shown not to correlate with ligand pKa over a range of approximately 10 pKa units, and a rationale for this is advanced. Additional ligand modifications were prepared in order to explore bulk tolerance at the enzyme oxygen binding site and to determine the effects of substituting a six-membered ligand group for the five-membered imidazole-2-thione ligand.

  DOI：

  10.1021/jm00164a051

文献信息

• 1-Aralkyl-1,2-dihydropyrimidine-2-thiones
  申请人：SMITHKLINE BECKMAN CORPORATION

  公开号：EP0323147A2

  公开（公告）日：1989-07-05

  Compounds of structure (I) and pharmaceutically acceptable acid addition salts thereof are described in which, n is 0 to 5; and X¹ to X⁵ are any accessible combination of hydrogen, halogen, C₁₋₆alkyl, C₁₋₆alkoxy, cyano, nitro, SONH₂, SO₂CH₃, SO₂CH₂F, SO₂CHF₂, SO₂CF₃, CF₃, CHO, OH, CH₂OH, CO₂H, CO₂CpH2p+1 wherein p is 1 to 4. These compounds are dopamine-β-hydroxylase inhibitors. Pharmaceutical compositions are described as are methods of use. Processes for the preparation of these compounds are described.

  结构(I)的化合物 及其药学上可接受的酸加成盐，其中，n 为 0 至 5；和 X¹ 至 X⁵ 是氢、卤素、C₁₋₆烷基、C₁₋₆烷氧基、氰基、硝基的任何可获得的组合、SONH₂、SO₂CH₃、SO₂CH₂F、SO₂CHF₂、SO₂CF₃、CF₃、CHO、OH、CH₂OH、CO₂H、CO₂CpH2p+1，其中 p 为 1 至 4。 这些化合物是多巴胺-β-羟化酶抑制剂。介绍了药物组合物以及使用方法。还描述了制备这些化合物的工艺。
• WO1989006131A1
  申请人：——

  公开号：WO1989006131A1

  公开（公告）日：1989-07-13
• Some benzyl-substituted imidazoles, triazoles, tetrazoles, pyridinethiones, and structural relatives as multisubstrate inhibitors of dopamine .beta.-hydroxylase. 4. Structure-activity relationships at the copper binding site
  作者：Lawrence I. Kruse、Carl Kaiser、Walter E. DeWolf、Joseph A. Finkelstein、James S. Frazee、Eileen L. Hilbert、Stephen T. Ross、Kathryn E. Flaim、John L. Sawyer

  DOI：10.1021/jm00164a051

  日期：1990.2

  Structure-activity relationships (SAR) were determined for novel multisubstrate inhibitors of dopamine beta-hydroxylase (DBH; EC 1.14.17.1) by examining the effects upon in vitro inhibitory potencies resulting from structural changes at the copper-binding region of inhibitor. Attempts were made to determine replacement groups for the thione sulfur atom of the prototypical inhibitor 1-(4-hydroxybenzyl)imidazole-2-thione described previously. The synthesis and evaluation of oxygen and nitrogen analogues of the soft thione group demonstrated the sulfur atom to be necessary for optimal activity. An additional series of imidazole-2-thione relatives was prepared in an effort to probe the relationship between the pKa of the ligand group and inhibitory potency. In vitro inhibitory potency was shown not to correlate with ligand pKa over a range of approximately 10 pKa units, and a rationale for this is advanced. Additional ligand modifications were prepared in order to explore bulk tolerance at the enzyme oxygen binding site and to determine the effects of substituting a six-membered ligand group for the five-membered imidazole-2-thione ligand.