3,5-difluorobenzyl isothiocyanate | 107186-81-2

• 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: 3,5-difluorobenzyl isothiocyanate
• 英文别名: 1,3-difluoro-5-(isothiocyanatomethyl)benzene
• CAS: 107186-81-2
• 化学式: C₈H₅F₂NS
• 分子量: 185.197
• InChiKey: SGIOZSSTJZSGAL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  12
• 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：
  44.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3,5-difluorobenzyl isothiocyanate 在 sodium ethanolate 作用下， 生成 3-Mercapto-4-[3,5-difluorobenzyl]-5-(pyridin-4-yl)-1,2,4-triazole
  参考文献：
  名称：

  Dopamine-beta hydroxylase inhibitors

  摘要：

  多巴胺-β-羟化酶抑制剂的结构：其中R¹为吡啶基或吡啶基烷基，包含它们的药物组合物以及它们在降低血压治疗中的用途。

  公开号：

  EP0359505A1
• 作为产物：
  描述：

  3,5-二氟苯甲腈 在 镍 氨 、 氢气 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 乙醚 为溶剂， -10.0~20.0 ℃ 、344.73 kPa 条件下， 反应 1.5h， 生成 3,5-difluorobenzyl isothiocyanate
  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

• 4-Aralkyl-5-substituted-1,2,4-triazole-5-thiols
  申请人：SMITHKLINE BECKMAN CORPORATION

  公开号：EP0323737A1

  公开（公告）日：1989-07-12

  Compounds of formula (I) and pharmaceutically acceptable salts thereof are described in which, n is 0 to 5; X¹ to X⁵ are any accessible combination of hydrogen, halogen, C₁₋₆alkyl, C₁₋₆alkoxy, cyano, nitro, SONH₂, SO₂NH₂, SO₂CH₃, SO₂CH₂F, SO₂CHF₂, SO₂CF₃, CF₃, CHO, OH, CH₂OH, CO₂H, or CO₂CpH2p+1 wherein p is 1 to 4; R¹ is phenyl substituted by X¹ to X⁵, C₁₋₄alkyl, C₃₋₆cycloalkyl, or an arylC₁₋₄alkyl group substituted by X¹ to X⁵; R² is hydrogen, C₁₋₄alkyl or (CH₂)m-CO₂R³; m is 0 to 5; and R³ is H or C₁₋₄alkyl. 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.

  描述了式（I）的化合物及其药学上可接受的盐，其中，n为0至5；X¹至X⁵为氢、卤素、C₁₋₆烷基、C₁₋₆烷氧基、氰基、硝基、SONH₂、SO₂NH₂、SO₂CH₃、SO₂CH₂F、SO₂CHF₂、SO₂CF₃、CF₃、CHO、OH、CH₂OH、CO₂H或CO₂CpH2p+1的任意可访问组合，其中p为1至4；R¹为被X¹至X⁵取代的苯基、C₁₋₄烷基、C₃₋₆环烷基或被X¹至X⁵取代的芳基C₁₋₄烷基基团；R²为氢、C₁₋₄烷基或（CH₂）m-CO₂R³；m为0至5；R³为H或C₁₋₄烷基。这些化合物是多巴胺-β-羟基化酶抑制剂。描述了药物组合物以及使用方法。描述了这些化合物的制备过程。
• 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。
• Novel Self-Assembly of <i>m</i>-Xylylene Type Dithioureas by Head-to-Tail Hydrogen Bonding
  作者：Yoshito Tobe、Shin-ichi Sasaki、Masaaki Mizuno、Keiji Hirose、Koichiro Naemura

  DOI：10.1021/jo980441p

  日期：1998.10.1

  Dithiourea 1a self-assembles to form an orthogonal dimer structure both in solution and in the solid state, wherein the four thiourea groups establish a closed network of hydrogen bonds through a head-to-tail binding mode. This novel dimer structure was elucidated on the basis of H-1 NMR spectra, vapor pressure osmometry, and X-ray crystal structure analysis. Furthermore, a series of m-xylylene type dithioureas were synthesized and their dimerization constants (K-a) in CDCl3 were determined by dilution experiments using H-1 NMR spectroscopy. The magnitude of the K-a values are dependent on the steric bulk of the side chains, the acidity of the thiourea groups, and the weak intermolecular interaction between the benzene rings of the side chains and the m-xylylene spacer.
• Self-assembled proline-amino thioureas as efficient organocatalysts for the asymmetric Michael addition of aldehydes to nitroolefins
  作者：Wan-Hui Wang、Takeshi Abe、Xiang-Bo Wang、Koichi Kodama、Takuji Hirose、Guang-You Zhang

  DOI：10.1016/j.tetasy.2010.11.025

  日期：2010.12

  A small co-catalyst library of amino thioureas has been established from chiral 1,3-diamines. These bifunctional thioureas can form assemblies with proline to cooperatively catalyze the asymmetric Michael addition of aldehydes to nitroolefins. Both the reaction rate (up to 98% yield for 18 h) and the enantioselectivity (up to 94% ee) were significantly improved upon in less polar solvents. (C) 2010 Elsevier Ltd. All rights reserved.