(R)-[3-(6,8-difluorochroman-3-yl)-2-thioxo-2,3-dihydro-1H-imidazol-4-ylmethyl]carbamic acid tert-butyl ester | 878806-94-1

• 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)-[3-(6,8-difluorochroman-3-yl)-2-thioxo-2,3-dihydro-1H-imidazol-4-ylmethyl]carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[[3-[(3R)-6,8-difluoro-3,4-dihydro-2H-chromen-3-yl]-2-sulfanylidene-1H-imidazol-4-yl]methyl]carbamate
• CAS: 878806-94-1
• 化学式: C₁₈H₂₁F₂N₃O₃S
• 分子量: 397.446
• InChiKey: ZCUBPZYNWFSBMC-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  94.9
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (R)-[3-(6,8-difluorochroman-3-yl)-2-thioxo-2,3-dihydro-1H-imidazol-4-ylmethyl]carbamic acid tert-butyl ester 在 盐酸 、 水 作用下， 以 乙酸乙酯 为溶剂， 反应 2.0h， 生成 (R)-5-aminomethyl-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione hydrochloride
  参考文献：
  名称：

  1, 3-Dihydroimidazoles for Treating Cardiovascular Disorders

  摘要：

  一种方法包括利用式I的化合物：其中R1，R2和R3相同或不同，并表示氢，卤素，烷基，烷基芳基，烷氧基，羟基，硝基，氨基，烷基羰基氨基，烷基氨基或二烷基氨基基团；R4表示氢，烷基或烷基芳基基团；X表示CH2，氧原子或硫原子；n为1，2或3，但当n为1时，X不是CH2；以及(R)-和(S)-对映体或对映体的混合物及其药学上可接受的盐；其中术语烷基表示含有一至六个碳原子的碳氢链，直链或支链，可选地被芳基，烷氧基，卤素，烷氧羰基或羟基羰基基团取代；术语芳基表示苯基或萘基，可选地被烷氧基，卤素或硝基取代；术语卤素表示氟，氯，溴或碘，在制备用于治疗以下一种或多种适应症的药物：充血性心力衰竭，心绞痛，心律失常，循环障碍，雷诺现象，偏头痛和焦虑症。

  公开号：

  US20100286219A1
• 作为产物：
  描述：

  tert-butyl (3-((tert-butyldimethylsilyl)oxy)-2-hydroxypropyl)carbamate 在 戴斯-马丁氧化剂 、 溶剂黄146 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 3.0h， 生成 (R)-[3-(6,8-difluorochroman-3-yl)-2-thioxo-2,3-dihydro-1H-imidazol-4-ylmethyl]carbamic 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

文献信息

• 1, 3-Dihydroimidazoles for Treating Cardiovascular Disorders
  申请人：Soares Da Silva Patricio Manuel Vieira Araújo

  公开号：US20100286219A1

  公开（公告）日：2010-11-11

  A method comprising utilizing a compound of formula I: where R 1 , R 2 and R 3 are the same or different and signify hydrogens, halogens, alkyl, alkylaryl, alkyloxy, hydroxy, nitro, amino, alkylcarbonylamino, alkylamino or dialkylamino group; R 4 signifies hydrogen, alkyl or alkylaryl group; X signifies CH 2 , oxygen atom or sulphur atom; n is 1, 2 or 3, with the proviso that when n is 1, X is not CH 2 ; and the individual (R)- and (S)-enantiomers or mixtures of enantiomers and pharmaceutically acceptable salts thereof; wherein the term alkyl means hydrocarbon chains, straight or branched, containing from one to six carbon atoms, optionally substituted by aryl, alkoxy, halogen, alkoxycarbonyl or hydroxycarbonyl groups; the term aryl means a phenyl or naphthyl group, optionally substituted by alkyloxy, halogen or nitro group; the term halogen means fluorine, chlorine, bromine or iodine, in the manufacture of a medicament for the treatment of one or more of the following indications: congestive heart failure, angina, arrhythmias, circulatory disorders, Raynaud's Phenomenon, migraine, and anxiety disorders.

  一种方法包括利用式I的化合物：其中R1，R2和R3相同或不同，并表示氢，卤素，烷基，烷基芳基，烷氧基，羟基，硝基，氨基，烷基羰基氨基，烷基氨基或二烷基氨基基团；R4表示氢，烷基或烷基芳基基团；X表示CH2，氧原子或硫原子；n为1，2或3，但当n为1时，X不是CH2；以及(R)-和(S)-对映体或对映体的混合物及其药学上可接受的盐；其中术语烷基表示含有一至六个碳原子的碳氢链，直链或支链，可选地被芳基，烷氧基，卤素，烷氧羰基或羟基羰基基团取代；术语芳基表示苯基或萘基，可选地被烷氧基，卤素或硝基取代；术语卤素表示氟，氯，溴或碘，在制备用于治疗以下一种或多种适应症的药物：充血性心力衰竭，心绞痛，心律失常，循环障碍，雷诺现象，偏头痛和焦虑症。
• Synthesis and Biological Evaluation of Novel, Peripherally Selective Chromanyl Imidazolethione-Based Inhibitors of Dopamine β-Hydroxylase
  作者：Alexandre Beliaev、David A. Learmonth、Patricio Soares-da-Silva

  DOI：10.1021/jm051051f

  日期：2006.2.1

  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.