2-butyl-4,5,6,7-tetrahydro-1H-benzimidazole | 138402-08-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-butyl-4,5,6,7-tetrahydro-1H-benzimidazole
• 英文别名: 2-n-butyl-4,5,6,7-tetrahydrobenzimidazole；1H-Benzimidazole, 2-butyl-4,5,6,7-tetrahydro-
• CAS: 138402-08-1
• 化学式: C₁₁H₁₈N₂
• 分子量: 178.277
• InChiKey: IXVFUAMUGPITMV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  28.7
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-butyl-4,5,6,7-tetrahydro-1H-benzimidazole 在 盐酸 、 sodium hydride 作用下， 以 乙醚 为溶剂， 反应 2.5h， 生成
  参考文献：
  名称：

  Amines That Transport Protons across Bilayer Membranes:  Synthesis, Lysosomal Neutralization, and Two-Phase pK_a Values by NMR

  摘要：

  It is desirable to be able to control the pH of lysosomes. A collection of lipophilic, nitrogenous bases, designed to act as membrane-active, catalytic proton transfer agents, were prepared and their effective pK(a)s measured in a vigorously stirred, two-phase system. One phase was a phosphate buffer whose pH was varied over the range ca, 1-11. The other was an immiscible, deuterated organic solvent in which the compounds preferentially resided even when protonated. When chemical shift changes versus the pH of the buffer were plotted, clear pK(a) curves were generated that are relevant to transmembrane proton transfer behavior. The two-phase pK(a)s increased with increasing counterion lipophilicity and with increasing organic solvent polarity, The compounds were also tested for their ability to neutralize the acidity of lysosomes, a model for other acidic vesicles involved in drug sorting. The most successful of these, imidazole 6a, has > 100 times the neutralizing power of ammonia, a standard lysosomotropic amine, causing a 1.7 unit rise in lysosomal pH of RAW cells at 0.1 mM, compared to a 0.2 and 1.4 unit rise for ammonium chloride at 0.1 and 10 mM, respectively.

  DOI：

  10.1021/jo960367f
• 作为产物：
  描述：

  戊腈 在 盐酸 、 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 2-butyl-4,5,6,7-tetrahydro-1H-benzimidazole
  参考文献：
  名称：

  Amines That Transport Protons across Bilayer Membranes:  Synthesis, Lysosomal Neutralization, and Two-Phase pK_a Values by NMR

  摘要：

  It is desirable to be able to control the pH of lysosomes. A collection of lipophilic, nitrogenous bases, designed to act as membrane-active, catalytic proton transfer agents, were prepared and their effective pK(a)s measured in a vigorously stirred, two-phase system. One phase was a phosphate buffer whose pH was varied over the range ca, 1-11. The other was an immiscible, deuterated organic solvent in which the compounds preferentially resided even when protonated. When chemical shift changes versus the pH of the buffer were plotted, clear pK(a) curves were generated that are relevant to transmembrane proton transfer behavior. The two-phase pK(a)s increased with increasing counterion lipophilicity and with increasing organic solvent polarity, The compounds were also tested for their ability to neutralize the acidity of lysosomes, a model for other acidic vesicles involved in drug sorting. The most successful of these, imidazole 6a, has > 100 times the neutralizing power of ammonia, a standard lysosomotropic amine, causing a 1.7 unit rise in lysosomal pH of RAW cells at 0.1 mM, compared to a 0.2 and 1.4 unit rise for ammonium chloride at 0.1 and 10 mM, respectively.

  DOI：

  10.1021/jo960367f

文献信息

• N-substituted heterocyclic derivatives, their preparation and the
  申请人：Elf Sanofi

  公开号：US05270317A1

  公开（公告）日：1993-12-14

  The invention relates to N-substituted heterocyclic derivatives and its salts. These derivatives have the formula ##STR1## in which the substituents are as defined in the specification. Application: Angiotensin II antagonists

  这项发明涉及N-取代杂环衍生物及其盐。这些衍生物的化学式为##STR1##其中取代基如规范中所定义。应用：血管紧张素Ⅱ拮抗剂
• A new series of imidazolones: highly specific and potent nonpeptide AT1 angiotensin II receptor antagonists
  作者：Claude A. Bernhart、Pierre M. Perreaut、Bernard P. Ferrari、Yvette A. Muneaux、Jean Louis A. Assens、Jacques Clement、Frederique Haudricourt、Claude F. Muneaux、Joelle E. Taillades、Marie-Aimee Vignal、Jean Gougat、Pierre R. Guiraudou、Colette A. Lacour、Alain Roccon、Catherine F. Cazaubon、Jean-Claude Breliere、Gerard Le Fur、Dino Nisato

  DOI：10.1021/jm00074a018

  日期：1993.10.1

  Starting from the structure of the novel nonpeptide AT1 receptor antagonist DuP 753 (losartan), a new series of potent antagonists was designed. In these compounds the central imidazole nucleus was replaced by the dihydroimidazol-4-one structure. The most active compounds had a spirocyclopentane or a spirocyclohexane ring in position 5. Like the imidazole series, the best substituents were the linear

  从新型非肽AT1受体拮抗剂DuP 753（氯沙坦）的结构出发，设计了一系列新的有效拮抗剂。在这些化合物中，中央咪唑核被二氢咪唑-4-酮结构取代。活性最高的化合物在5位有一个螺环戊烷或一个螺环己烷环。与咪唑系列一样，最好的取代基是1位的线性丁基链和1位的[2'-（（四唑-5-基）联苯基]甲基] 3.通过化合物竞争性抑制[125I] AII与AT1亚型受体结合并拮抗AII诱导的兔主动脉环收缩的能力来评估拮抗活性。活性最高的化合物的IC50值在纳摩尔范围内。在清醒的老鼠中 当口服时，化合物4和21拮抗AII升压反应。化合物21（SR 47436）最活泼；最近显示它在静脉和口服中对食蟹猴也具有活性。该分子目前正在接受治疗高血压的临床试验。
• US5270317A
  申请人：——

  公开号：US5270317A

  公开（公告）日：1993-12-14
• US5352788A
  申请人：——

  公开号：US5352788A

  公开（公告）日：1994-10-04
• US5559233A
  申请人：——

  公开号：US5559233A

  公开（公告）日：1996-09-24