1-(3,5-二氟苄基)-2,3-二氢-1H-咪唑 | 95333-81-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 1-(3,5-二氟苄基)-2,3-二氢-1H-咪唑
• 英文名称: 1-(3,5-difluorobenzyl)imidazole-2-thiol
• 英文别名: SKF102698；1-(3',5'-Difluorobenzyl)-2-mercaptoimidazole；1-(3,5-difluorobenzyl)-2-mercaptoimidazole；3-[(3,5-difluorophenyl)methyl]-1H-imidazole-2-thione
• CAS: 95333-81-6
• 化学式: C₁₀H₈F₂N₂S
• 分子量: 226.25
• InChiKey: WPMVQUHUCQAOBU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 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：
  3

反应信息

• 作为反应物：
  描述：

  1-(3,5-二氟苄基)-2,3-二氢-1H-咪唑 在 氢氧化钾 作用下， 以 N-甲基乙酰胺 、 二氯甲烷 、 水 为溶剂， 生成 2-(2-carbomethoxyethylthio)-1-(3,5-difluorobenzyl)imidazole
  参考文献：
  名称：

  Dopamine-.beta.-hydroxylase inhibitors

  摘要：

  具有以下式子的有效多巴胺-β-羟化酶抑制剂##STR1##，可用于抑制哺乳动物中的多巴胺-β-羟化酶活性，包括这些抑制剂的制药组合物以及使用这些抑制剂抑制哺乳动物中的多巴胺-β-羟化酶活性的方法。

  公开号：

  US04935438A1
• 作为产物：
  描述：

  1-溴-3,5-二氟苯 在 镍 盐酸 、 sodium tetrahydroborate 、 甲酸 作用下， 以 乙醇 、 N,N-二甲基乙酰胺 、 水 为溶剂， 反应 32.33h， 生成 1-(3,5-二氟苄基)-2,3-二氢-1H-咪唑
  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

• Renal-selective prodrugs for control of renal sympathetic nerve activity in the treatment of hypertension
  申请人：G.D. Searle & Co.

  公开号：US20030220521A1

  公开（公告）日：2003-11-27

  Renal-selective prodrugs are described which are preferentially converted in the kidney to compounds capable of inhibiting synthesis of catecholamine-type neurotransmitters involved in renal sympathetic nerve activity. The prodrugs described herein are derived from inhibitor compounds capable of inhibiting one or more of the enzymes involved in catecholamine synthesis, such compounds being classifiable as tyrosine hydroxylase inhibitors, or as dopa-decarboxylase inhibitors, or as dopamine-&bgr;-hydroxylase inhibitors. These inhibitor compounds are linked to a chemical moiety, such as a glutamic acid derivative, by a cleavable bond which is recognized selectively by enzymes located predominantly in the kidney. The liberated inhibitor compound is then available in the kidney to inhibit one or more of the enzymes involved in catecholamine synthesis. Inhibition of renal catecholamine synthesis can suppress heightened renal nerve activity associated with sodium-retention related disorders such as hypertension. Conjugates of particular interest are glutamyl derivatives of dopamine-&bgr;-hydroxylase inhibitors, of which N-acetyl-&ggr;-glutamyl fusaric acid hydrazide (shown below) is preferred. 1

  本文描述了一种肾选择性的前药，其在肾脏中优先转化为能够抑制参与肾交感神经活动的儿茶酚型神经递质合成的化合物。本文所描述的前药来源于能够抑制儿茶酚合成中的一个或多个酶的抑制剂化合物，这些化合物可分类为酪氨酸羟化酶抑制剂，多巴脱羧酶抑制剂或多巴胺-&bgr;-羟化酶抑制剂。这些抑制剂化合物通过可被肾脏中大量存在的酶选择性识别的可裂解键与化学基团（如谷氨酸衍生物）连接。释放的抑制剂化合物然后可在肾脏中用于抑制儿茶酚合成中的一个或多个酶。抑制肾脏儿茶酚合成可抑制与钠潴留相关的疾病（如高血压）相关的增强肾脏神经活动。特别感兴趣的共轭物是多巴胺-&bgr;-羟化酶抑制剂的谷氨酰衍生物，其中N-乙酰-&ggr;-谷氨酰富萨酸肼（如下图所示）是首选。1
• 2-(aminoalkylthio)imidazoles as dopamine-.beta.-hydroxylase inhibitors
  申请人：SmithKline Beckman Corporation

  公开号：US04882348A1

  公开（公告）日：1989-11-21

  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 mannals. Also disclosed are novel intermediates useful in preparing the presently invented inhibitors.

  具有以下公式的有效多巴胺-β-羟化酶抑制剂##STR1##，用于抑制多巴胺-β-羟化酶活性，包括这些抑制剂的制药组合物，并使用这些抑制剂抑制哺乳动物中的多巴胺-β-羟化酶活性的方法。还揭示了用于制备目前发明的抑制剂的新型中间体。
• Medicaments
  申请人：Smith Kline & French Laboratories Limited

  公开号：US05326781A1

  公开（公告）日：1994-07-05

  Benzylimidazole derivatives are described as anxiolytic agents.

  苯甲基咪唑衍生物被描述为抗焦虑药物。
• Intermediate to dopamine-.beta.-hydroxylase inhibitors
  申请人：SmithKline Beckman Corporation

  公开号：US04912226A1

  公开（公告）日：1990-03-27

  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.

  具有公式##STR1##的有效多巴胺-β-羟化酶抑制剂，可用于抑制哺乳动物中的多巴胺-β-羟化酶活性，包括这些抑制剂的制药组合物以及使用这些抑制剂抑制哺乳动物中的多巴胺-β-羟化酶活性的方法。还披露了用于制备目前发明的抑制剂的新型中间体。
• Renal-selective prodrugs for control of renal smpathetic nerve activity in the treatment of hypertension
  申请人：G.D. Searle & Co.

  公开号：US20040101523A1

  公开（公告）日：2004-05-27

  Renal-selective prodrugs are described which are preferentially converted in the kidney to compounds capable of inhibiting synthesis of catecholamine-type neurotransmitters involved in renal sympathetic nerve activity. The prodrugs described herein are derived from inhibitor compounds capable of inhibiting one or more of the enzymes involved in catecholamine synthesis, such compounds being classifiable as tyrosine hydroxylase inhibitors, or as dopa-decarboxylase inhibitors, or as dopamine-&bgr;-hydroxylase inhibitors. These inhibitor compounds are linked to a chemical moiety, such as a glutamic acid derivative, by a cleavable bond which is recognized selectively by enzymes located predominantly in the kidney. The liberated inhibitor compound is then available in the kidney to inhibit one or more of the enzymes involved in catecholamine synthesis. Inhibition of renal catecholamine synthesis can suppress heightened renal nerve activity associated with sodium-retention related disorders such as hypertension. Conjugates of particular interest are glutamyl derivatives of dopamine-&bgr;-hydroxylase inhibitors, of which N-acetyl-&ggr;-glutamyl fusaric acid hydrazide (shown below) is preferred. 1

  本文描述了肾脏选择性前药，这些前药被优先转化为能够抑制与肾脏交感神经活动相关的儿茶酚类神经递质合成的化合物。所述前药源自能够抑制儿茶酚类合成中涉及的一个或多个酶的抑制剂化合物，这些化合物可分类为酪氨酸羟化酶抑制剂，或多巴脱羧酶抑制剂，或是多巴胺-β-羟化酶抑制剂。这些抑制剂化合物与化学基团（例如谷氨酸衍生物）通过可被肾脏内的酶特异性识别的可切断键连接。被释放的抑制剂化合物随后可在肾脏中抑制一个或多个涉及儿茶酚类合成的酶。抑制肾脏儿茶酚类合成可以抑制与钠潴留相关的疾病（如高血压）所伴随的过度肾脏神经活动。特别感兴趣的结合物是多巴胺-β-羟化酶抑制剂的谷氨酰衍生物，其中N-乙酰-γ-谷氨酰菌核酸酸肼（如下图所示）是首选。1