(R)-5-(2-aminoethyl)-1-(6-hydroxy-7-benzylchroman-3-yl)-1,3-dihydroimidazole-2-thione hydrochloride

• 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)-5-(2-aminoethyl)-1-(6-hydroxy-7-benzylchroman-3-yl)-1,3-dihydroimidazole-2-thione hydrochloride
• 英文别名: (R)-5-(2-aminoethyl)-1-(6-hydroxy-7-benzylchroman-3-yl)-1,3-dihydro-2H-imidazole-2-thione hydrochloride；4-(2-aminoethyl)-3-[(3R)-7-benzyl-6-hydroxy-3,4-dihydro-2H-chromen-3-yl]-1H-imidazole-2-thione;hydrochloride
• 化学式: C₂₁H₂₃N₃O₂S*ClH
• 分子量: 417.959
• InChiKey: ACWBKKDYNFMQTI-GMUIIQOCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.94
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  103
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  tert-butyl 1-[(3R)-7-benzyl-6-hydroxy-3,4-dihydro-2H-chromen-3-yl]-2-sulfanylidene-3a,5,6,6a-tetrahydro-3H-pyrrolo[2,3-d]imidazole-4-carboxylate 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-hydroxy-7-benzylchroman-3-yl)-1,3-dihydroimidazole-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

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。
• Peripherally-selective inhibitors of dopamine-beta-hydroxylase and method of their preparation
  申请人：Portela & C.A., S.A.

  公开号：US20040142996A1

  公开（公告）日：2004-07-22

  Compounds of formula I: t,0010 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 is CH 2 , O or S, and n is 1, 2 or 3, with the proviso that if X is CH 2 , n is not 1, and a method for their preparation. The compounds have potentially valuable pharmaceutical properties for the treatment of cardiovascular disorders such as hypertension and chronic heart failure.

  式I的化合物：其中R1、R2和R3相同或不同，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为CH2、O或S，n为1、2或3，但如果X为CH2，则n不为1；以及它们的制备方法。这些化合物具有潜在的有价值的药理特性，可用于治疗心血管疾病，如高血压和慢性心力衰竭。
• Method of preparation of 3-(1,3-Dihydroimidazole-2-thione-1-yl)-chromanes and thiochromanes as dopamine-beta-hydroxylase inhibitors
  申请人：Portela & Ca., S.A.

  公开号：EP1911757A2

  公开（公告）日：2008-04-16

  A process for the preparation of the individual (R)- and (S)-enantiomers or mixtures of enantiomers and pharmaceutically acceptable salts of a compound of formula 1: where R1, R2 and R3 are the same or different and signify hydrogens, halogens, alkyl, alkyloxy, hydroxy, nitro, amino, alkylcarbonylamino, alkylamino or dialkylamino group; R4 signifies hydrogen, alkyl or alkylaryl group; X signifies CH2, oxygen atom or sulphur atom; n is 1, 2 or 3, with the proviso that when n is 1, X is not CH2

  一种制备式 1 化合物的单个 (R) - 和 (S) - 对映体或对映体混合物以及药学上可接受的盐的工艺： 其中 R1、R2 和 R3 相同或不同，表示氢、卤素、烷基、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；R4 表示氢、烷基或烷基芳基；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。
• Chromane and thiochromane-3-yl-1,3-dihydroimidazoles as inhibitors of dopamine-beta-hydroxylase and methods of their preparation
  申请人：Portela & Ca., S.A.

  公开号：EP1908760A1

  公开（公告）日：2008-04-09

  Compounds of formula I and a method for their preparation are described: where X is CH2, O or S, and n is 1, 2 or 3, with the proviso that if X is CH2, n is not 1. The compounds have potentially valuable pharmaceutical properties for the treatment of cardiovascular disorders such as hypertension and chronic heart failure.

  描述了式 I 化合物及其制备方法： 其中 X 是 CH2、O 或 S，n 是 1、2 或 3，但如果 X 是 CH2，则 n 不是 1。 这些化合物具有治疗高血压和慢性心力衰竭等心血管疾病的潜在药物价值。
• Peripherally-selective inhibitors of dopamine-b-hydroxylase and method of their preparation
  申请人：Portela & Ca., S.A.

  公开号：EP1914233A1

  公开（公告）日：2008-04-23

  A compound of formula III wherein (1) when n signifies 2, R4 signifies hydrogen, alkyl group or alkylaryl group; R5 signifies a hydroxyl protecting group and R6 signifies an amino protecting group; or (2) when n signifies 3, R5 signifies a hydroxyl protecting group; and R4 and R6 taken together represent a phthalimido group and wherein the hydroxyl protecting group is an organosilyl group; the amino protecting group is an alkyl carbamate or alkylaryl carbamate group; 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 alkoxy, halogen or nitro group; and the term halogen means fluorine, chlorine, bromine or iodine.

  式 III 的化合物 其中 (1) 当 n 表示 2 时，R4 表示氢、烷基或烷基芳基；R5 表示羟基保护基团，R6 表示氨基保护基团；或 (2) 当 n 表示 3 时，R5 表示羟基保护基团；R4 和 R6 合在一起表示邻苯二甲酰亚胺基团 其中羟基保护基团为有机硅基团；氨基保护基团为氨基甲酸烷基酯或氨基甲酸烷基芳基酯基团；术语烷基指含有 1 至 6 个碳原子的直链或支链烃链，可选择被芳基、烷氧基、卤素、烷氧基羰基或羟基羰基取代；术语芳基指苯基或萘基，可选择被烷氧基、卤素或硝基取代；术语卤素指氟、氯、溴或碘。