(R)-1-(6-chloro-8-methoxychroman-3-yl)-2-thioxohexahydropyrrolo[2,3-d]imidazole-4-carboxylic acid tert-butyl ester

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: (R)-1-(6-chloro-8-methoxychroman-3-yl)-2-thioxohexahydropyrrolo[2,3-d]imidazole-4-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl 1-[(3R)-6-chloro-8-methoxy-3,4-dihydro-2H-chromen-3-yl]-2-sulfanylidene-3a,5,6,6a-tetrahydro-3H-pyrrolo[2,3-d]imidazole-4-carboxylate
• 化学式: C₂₀H₂₆ClN₃O₄S
• 分子量: 439.963
• InChiKey: AERHMYVBSDSLLX-TUBUQKNSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  95.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-1-(6-chloro-8-methoxychroman-3-yl)-2-thioxohexahydropyrrolo[2,3-d]imidazole-4-carboxylic acid tert-butyl ester 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 反应 2.0h， 生成 (R)-5-(2-aminoethyl)-1-(6-chloro-8-methoxychroman-3-yl)-1,3-dihydro-2H-imidazole-2-thione hydrochloride
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Novel, Peripherally Selective Chromanyl Imidazolethione-Based Inhibitors of Dopamine β-Hydroxylase

  摘要：

  A novel series of dopamine beta-hydroxylase (DBH) inhibitors was designed and synthesized incorporating modifications to the core structure of nepicastat 3, with the principal aim of discovering potent DBH inhibitors exerting minimal effects on dopamine (DA) and noradrenaline (NA) levels in the central nervous system. This study resulted in the identification of a potent, peripherally selective DBH inhibitor, (R)-5-(2-aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione hydrochloride 54 (BIA 5-453). In experiments in mice and rats at T-max (9 h after administration), 54 reduced NA levels in a dose-dependent manner in both the left atrium and the left ventricle, with the maximal inhibitory effect attained at a dose of 100 mg/kg. In contrast to that found in the heart, 54 failed to affect NA tissue levels in the brain. Compound 54 is thus presented as a candidate for clinical evaluation for the treatment of chronic heart failure and hypertension.

  DOI：

  10.1021/jm051051f
• 作为产物：
  描述：

  [4-((tert-butyldimethylsilanyl)oxy)-3-oxobutyl]carbamic acid tert-butyl ester 、 、 potassium thioacyanate 在 溶剂黄146 作用下， 以 乙酸乙酯 为溶剂， 反应 7.0h， 以48%的产率得到(R)-1-(6-chloro-8-methoxychroman-3-yl)-2-thioxohexahydropyrrolo[2,3-d]imidazole-4-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Novel, Peripherally Selective Chromanyl Imidazolethione-Based Inhibitors of Dopamine β-Hydroxylase

  摘要：

  A novel series of dopamine beta-hydroxylase (DBH) inhibitors was designed and synthesized incorporating modifications to the core structure of nepicastat 3, with the principal aim of discovering potent DBH inhibitors exerting minimal effects on dopamine (DA) and noradrenaline (NA) levels in the central nervous system. This study resulted in the identification of a potent, peripherally selective DBH inhibitor, (R)-5-(2-aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione hydrochloride 54 (BIA 5-453). In experiments in mice and rats at T-max (9 h after administration), 54 reduced NA levels in a dose-dependent manner in both the left atrium and the left ventricle, with the maximal inhibitory effect attained at a dose of 100 mg/kg. In contrast to that found in the heart, 54 failed to affect NA tissue levels in the brain. Compound 54 is thus presented as a candidate for clinical evaluation for the treatment of chronic heart failure and hypertension.

  DOI：

  10.1021/jm051051f