4-(3,5-difluoro-4-methoxybenzyl)-1,2,4-triazole-3-thione | 107186-79-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-(3,5-difluoro-4-methoxybenzyl)-1,2,4-triazole-3-thione
• 英文别名: 4-[(3,5-difluoro-4-methoxyphenyl)methyl]-1H-1,2,4-triazole-5-thione
• CAS: 107186-79-8
• 化学式: C₁₀H₉F₂N₃OS
• 分子量: 257.264
• InChiKey: WKHPPAMVYHAMFN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  69
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(3,5-difluoro-4-methoxybenzyl)-1,2,4-triazole-3-thione 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以23%的产率得到4-(3,5-difluoro-4-hydroxybenzyl)-1,2,4-triazole-3-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-4-甲氧基苯甲氰 在 镍 氨 、 氢气 、 sodium ethanolate 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 乙醚 、 乙醇 为溶剂， -10.0~20.0 ℃ 、344.73 kPa 条件下， 反应 28.5h， 生成 4-(3,5-difluoro-4-methoxybenzyl)-1,2,4-triazole-3-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

• Dopamine-.beta.-hydroxylase inhibitors
  申请人：SmithKlein Beckman Corporation

  公开号：US04628059A1

  公开（公告）日：1986-12-09

  Potent dopamine-.beta.-hydroxylase inhibitors having the Formula ##STR1## that are useful to inhibit dopamine-.beta.-hydroxylase activity, pharmaceutical compositions including these inhibitors, and methods of using these inhibitors to inhibit dopamine-.beta.-hydroxylase activity in mammals. Also disclosed are novel intermediates useful in preparing the presently invented inhibitors.

  具有以下化学式##STR1##的有效多巴胺-β-羟基化酶抑制剂，用于抑制多巴胺-β-羟基化酶活性，包括这些抑制剂的药物组合物，以及使用这些抑制剂在哺乳动物中抑制多巴胺-β-羟基化酶活性的方法。还披露了在制备目前发明的抑制剂时有用的新型中间体。
• Dopamine-beta-hydroxylase inhibitors
  申请人：SMITHKLINE BECKMAN CORPORATION

  公开号：EP0225718A2

  公开（公告）日：1987-06-16

  Compounds of formula in which: n is 0-5; R is hydrogen or C1-4 alkyl; and X is hydrogen, halo, C1-4 alkyl, CN, N02 S02NH2, COOH, CHO, OH, CH20H, C1-4 alkoxy, CF3, S02CH3, S02CF3, or CO2CaH2a+1 where a is 1-5, or any accessible combination thereof of up to 5 substituents; processes for their preparation, intermediates useful in their preparation, pharmaceutical compositions containing them and their use in therapy as dopamine-β-hydroxylase inhibitors.

  式中的化合物，其中：n 为 0-5；R 为氢或 C1-4 烷基；X 为氢、卤代、C1-4 烷基、CN、N02 S02NH2、COOH、CHO、OH、CH20H、C1-4 烷氧基、CF3、S02CH3、S02CF3 或 CO2CaH2a+1 其中 a 为 1-5，或其中最多 5 个取代基的任何可获得的组合；其制备工艺、制备过程中有用的中间体、含有它们的药物组合物以及它们作为多巴胺-β-羟化酶抑制剂在治疗中的用途。
• ——
  作者：FINKELSTEIN J. A.、 KAISER C.、 KRUSE L. I.

  DOI：——

  日期：——
• US4628059A
  申请人：——

  公开号：US4628059A

  公开（公告）日：1986-12-09
• 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.