1-(2,4-Dichloro-benzyl)-1,3-dihydro-imidazole-2-thione | 95333-76-9

• 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-(2,4-Dichloro-benzyl)-1,3-dihydro-imidazole-2-thione
• 英文别名: 3-[(2,4-dichlorophenyl)methyl]-1H-imidazole-2-thione
• CAS: 95333-76-9
• 化学式: C₁₀H₈Cl₂N₂S
• 分子量: 259.159
• InChiKey: MKOFKSXCLASLCV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  47.4
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  1-(2,4-dichlorophenyl)-N-(2,2-dimethoxyethyl)methanimine 在 盐酸 、 sodium tetrahydroborate 作用下， 以 乙醇 、 水 为溶剂， 反应 26.0h， 生成 1-(2,4-Dichloro-benzyl)-1,3-dihydro-imidazole-2-thione
  参考文献：
  名称：

  Multisubstrate inhibitors of dopamine .beta.-hydroxylase. 2. Structure-activity relationships at the phenethylamine binding site

  摘要：

  1-Aralkylimidazole-2-thiones have been shown to be potent multisubstrate inhibitors of dopamine beta-hydroxylase (DBH; EC 1.14.17.1). In the present study, a series of 1-benzylimidazole-2-thiones was prepared to explore the effects of substitution in the benzyl ring on the inhibition of DBH. A detailed structure-activity relationship for in vitro activity was discovered and this was shown by a modified Hansch analysis to correlate (r = 0.91) with four key structural features of the benzyl ring: the presence of a hydroxyl at the 4-position, molar refractivity at the 3-, 4-, and 5-positions, inductive effects of the substituents at the 3-, 4-, and 5-positions, and pi-electron density. The affinity (Kis) of eight substituted inhibitors for DBH was shown to correlate (r = 0.75) with the affinity (KD) of comparably substituted tyramines for the ternary DBH-oxygen-tyramine complex. This correlate is used to support the hypothesis that binding of inhibitor to DBH occurs in a fashion that mimics the binding of tyramine substrates. The most potent inhibitors were selected for study in vivo in the spontaneously hypertensive rat model of hypertension. The changes in vascular dopamine and norepinephrine levels that resulted from oral administration of the inhibitors corresponded to the observed reduction in mean arterial blood pressure. A divergence between in vitro potency and in vivo efficacy upon oral dosing was noted and is suggested to result from an in vivo metabolic conjugation of the phenolic group of inhibitor.

  DOI：

  10.1021/jm00386a008

文献信息

• Dopamine-beta-hydroxylase inhibitors
  申请人：SMITHKLINE BECKMAN CORPORATION

  公开号：EP0125033A1

  公开（公告）日：1984-11-14

  Compounds of formula:- wherein X is -H, -OH, halogen, C1-48alkyl, -CN, NO2, -SO2NH2, -CO2H, -CONH2, -CHO, -CH2OH. -CF3, -OCH3, -SO2C1-4alkyl, -SO2C1-4fluoroalkyl, or-CO2C1-4alkyl or any accessible combination thereof up to four substituents; Y is -H, -OH, halogen, C1-4alkyl, -CN, -NOz, -SO2NH2, -COzH, -CONH2, -CHO, -CHzOH, -CF3, -SO2C1-4alkyl, -SO2C1-4afiuoroalkyl, or -CO2C1-4alkyl; and R is -H or C1-4alkyl; and, n is 0-4, intermediates and processes for their preparation, pharmaceutical compositions containing them and their use in inhibiting DBH activity in mammals are described.

  式中化合物 式中 X是-H、-OH、卤素、C1-48烷基、-CN、NO2、-SO2NH2、-CO2H、-CONH2、-CHO、-CH2OH。-CF3、-OCH3、-SO2C1-4烷基、-SO2C1-4氟烷基或-CO2C1-4烷基或其中最多四个取代基的任何可获得的组合； Y 是-H、-OH、卤素、C1-4烷基、-CN、-NOz、-SO2NH2、-COzH、-CONH2、-CHO、-CHzOH、-CF3、-SO2C1-4烷基、-SO2C1-4氟烷基或-CO2C1-4烷基；以及 R 是-H 或 C1-4 烷基；以及 n 为 0-4、 所述中间体及其制备工艺、含有这些中间体的药物组合物以及它们在抑制哺乳动物体内 DBH 活性方面的用途。
• Intermediates useful in the preparation of dopamine-beta-hydroxylase inhibitors
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：EP0212066B1

  公开（公告）日：1990-11-22
• DOPAMINE- -HYDROXYLASE INHIBITORS
  申请人：SMITHKLINE BECKMAN CORPORATION

  公开号：EP0288488A1

  公开（公告）日：1988-11-02
• EP0288488A4
  申请人：——

  公开号：EP0288488A4

  公开（公告）日：1990-09-12
• [EN] DOPAMINE-ss-HYDROXYLASE INHIBITORS
  申请人：SMITHKLINE BECKMAN CORPORATION

  公开号：WO1988001267A1

  公开（公告）日：1988-02-25

  (EN) Potent DBH inhibitors having formula (I) can be used to inhibit DBH activity in mammals.(FR) Des inhibiteurs puissants de DBH ayant la formule (I) peuvent être utilisés pour inhiber l'activité de la DBH chez les mammifères.