1-(tert-butoxycarbonyl)-2-(3,5-difluorobenzyl)-4-tert-butylthiosemicarbazide | 123566-49-4

• 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: 1-(tert-butoxycarbonyl)-2-(3,5-difluorobenzyl)-4-tert-butylthiosemicarbazide
• 英文别名: 1-t-butoxycarbonyl-2-(3',5'-difluorobenzyl)-4-t-butylthiosemicarbazide；tert-butyl N-[tert-butylcarbamothioyl-[(3,5-difluorophenyl)methyl]amino]carbamate
• CAS: 123566-49-4
• 化学式: C₁₇H₂₅F₂N₃O₂S
• 分子量: 373.467
• InChiKey: VCIYYGKFOLVOEN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  85.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(tert-butoxycarbonyl)-2-(3,5-difluorobenzyl)-4-tert-butylthiosemicarbazide 在 甲酸 作用下， 反应 4.0h， 以22%的产率得到1-(3,5-difluorobenzyl)-1,2,4-triazole-5-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
• 作为产物：
  描述：

  3,5-二氟苯甲醛 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 、 正己烷 、 乙酸乙酯 为溶剂， 反应 12.0h， 生成 1-(tert-butoxycarbonyl)-2-(3,5-difluorobenzyl)-4-tert-butylthiosemicarbazide
  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

• Dopamine-beta-hydroxylase inhibitors
  申请人：——

  公开号：EP0246888A3

  公开（公告）日：1988-09-28

  Compounds of Formula : in which n is 0 to 5, R is hydrogen or C1-4alkyl and X is hydrogen, halo, C1-4alkyl, CN, NO₂, SO₂NH₂, COOH, CHO, OH, CH₂OH, C1-4alkoxy, CF₃, SO₂CH₃, SO₂CF₃ or CO₂CaH2a+1 wherein a is 1 to 5 or any synthetically accessible combination thereof of up to 5 substituents or any pharmaceutically acceptable salt or hydrate thereof, processes for their preparation, pharmaceutical compositions containing them and their use in therapy as dopamine β-hydroxylase inhibitors.

  化合物的化学式：其中n为0至5，R为氢或C1-4烷基，X为氢、卤素、C1-4烷基、CN、NO₂、SO₂NH₂、COOH、CHO、OH、CH₂OH、C1-4烷氧基、CF₃、SO₂CH₃、SO₂CF₃或CO₂CaH2a+1，其中a为1至5或最多具有5个取代基或任何可合成获得的组合物，或其任何药学上可接受的盐或水合物，其制备方法，含有它们的药物组合物以及它们在治疗中作为多巴胺β-羟化酶抑制剂的用途。
• 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.