2-丁基-4-氯-1-[(4-硝基苯基)甲基]-1H-咪唑-5-甲醇 | 114799-92-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 2-丁基-4-氯-1-[(4-硝基苯基)甲基]-1H-咪唑-5-甲醇
• 英文名称: 2-butyl-4-chloro-5-(hydroxymethyl)-1-<4-(nitrophenyl)methyl>imidazole
• 英文别名: 2-n-butyl-4-chloro-5-(hydroxymethyl)-1-<(4-nitrophenyl)methyl>imidazole；2-Butyl-4-chloro-1-[(4-nitrophenyl)methyl]-1H-imidazole-5-methanol；2-n-butyl-4-chloro-5-hydroxymethyl-1-(4-nitrobenzyl)imidazole；1-(4-Nitrobenzyl)-2-butyl-4-chloro-5-hydroxymethyl imidazole；[2-butyl-5-chloro-3-[(4-nitrophenyl)methyl]imidazol-4-yl]methanol
• CAS: 114799-92-7
• 化学式: C₁₅H₁₈ClN₃O₃
• 分子量: 323.779
• InChiKey: VZCRMLBEZOXEOO-UHFFFAOYSA-N

物化性质

• 沸点：
  525.6±45.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  83.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-丁基-4-氯-1-[(4-硝基苯基)甲基]-1H-咪唑-5-甲醇 在 盐酸 、 磺酰氯 、 sodium hydride 作用下， 反应 24.5h， 生成 3-[2-Butyl-5-chloro-3-(4-nitro-benzyl)-3H-imidazol-4-yl]-propionic acid
  参考文献：
  名称：

  Nonpeptide angiotensin II receptor antagonists. 1. Synthesis and in vitro structure-activity relationships of 4-[[[(1H-pyrrol-1-ylacetyl)amino]phenyl]methyl]imidazole derivatives as angiotensin II receptor antagonists

  摘要：

  A novel series of non-biphenylyltetrazole angiotensin II receptor antagonists which contain a 1H-pyrrol-1-ylacetyl residue in place of the benzoyl residue in EXP 6803 have been developed. The receptor binding activity of several members of this new series was in the 10(-8) M range, which was better than that of EXP 6803. Introduction of a carboxylic acid moiety at the 2-position of the pyrrole ring enhanced the in vitro binding affinity at the receptor by 10-fold. Compounds containing an acetic acid (18) or a propionic acid residue (20) at the 5-position of the imidazole were more potent than the carboxylic acid analogue (24). The binding IC50 of the most potent compound 20 was 22 nM. Compounds 18, 20, and 24 in their best fit conformations were manually overlayed on that of the template conformation of EXP 6803 and EXP 8623, respectively. The synthesis and structure-activity relationship data are described.

  DOI：

  10.1021/jm00064a007
• 作为产物：
  描述：

  2-丁基-4-氯-5-(羟甲基)咪唑 、 对硝基溴化苄 在 base 作用下， 生成 2-丁基-4-氯-1-[(4-硝基苯基)甲基]-1H-咪唑-5-甲醇
  参考文献：
  名称：

  Nonpeptide angiotensin II receptor antagonists. 1. Synthesis and in vitro structure-activity relationships of 4-[[[(1H-pyrrol-1-ylacetyl)amino]phenyl]methyl]imidazole derivatives as angiotensin II receptor antagonists

  摘要：

  A novel series of non-biphenylyltetrazole angiotensin II receptor antagonists which contain a 1H-pyrrol-1-ylacetyl residue in place of the benzoyl residue in EXP 6803 have been developed. The receptor binding activity of several members of this new series was in the 10(-8) M range, which was better than that of EXP 6803. Introduction of a carboxylic acid moiety at the 2-position of the pyrrole ring enhanced the in vitro binding affinity at the receptor by 10-fold. Compounds containing an acetic acid (18) or a propionic acid residue (20) at the 5-position of the imidazole were more potent than the carboxylic acid analogue (24). The binding IC50 of the most potent compound 20 was 22 nM. Compounds 18, 20, and 24 in their best fit conformations were manually overlayed on that of the template conformation of EXP 6803 and EXP 8623, respectively. The synthesis and structure-activity relationship data are described.

  DOI：

  10.1021/jm00064a007

文献信息

• The discovery of potent nonpeptide angiotensin II receptor antagonists: a new class of potent antihypertensives
  作者：John V. Duncia、Andrew T. Chiu、David J. Carini、George B. Gregory、Alexander L. Johnson、William A. Price、Gregory J. Wells、Pancras C. Wong、Joseph C. Calabrese、Pieter B. M. W. M. Timmermans

  DOI：10.1021/jm00167a007

  日期：1990.5

  A new class of potent antihypertensives has been discovered that exert their effect through blockade of the angiotensin II (AII) receptor. Most AII antagonists reported so far are peptide mimics of the endogenous vasoconstrictor octapeptide angiotensin II. The compounds of this paper are nonpeptides and therefore constitute a new class of potent AII receptor antagonists. Based on the overlap of a conformation

  已经发现了一类新型的有效降压药，它们通过阻断血管紧张素II（AII）受体发挥作用。迄今为止，大多数报道的AII拮抗剂都是内源性血管收缩八肽血管紧张素II的肽模拟物。本文的化合物是非肽，因此构成了一类新的有效的AII受体拮抗剂。基于AII构象与文献铅3的重叠，提出了一个假设，提示需要额外的酸性功能以增加铅的效力。通过系统的SAR研究，对另一种羧酸的取代导致对二酸4的观察到的结合亲和力增加了10倍。对于后续化合物的结合亲和力最终比文献上的结果增加了1000倍。因此，例如，对于化合物前导1，AII受体结合亲和力[IC50（microM）]为15 microM，对于化合物33和53，增加到0.018和0.012 microM。已经发现结构亲和关系需要存在四个关键具有良好活性的元素：（1）在苄基咪唑核的N-苄基对位上有一个额外的苯环，（2）在末端芳环的邻位上有一个酸性官能团，（3）在咪唑上有一个亲脂
• Angiotensin II receptor blocking imidazoles
  申请人：E. I. Du Pont de Nemours and Company

  公开号：US05138069A1

  公开（公告）日：1992-08-11

  Substituted imidazoles such as ##STR1## are useful as angiotensin II blockers. These compounds have activity in treating hypertension and congestive heart failure.

  取代咪唑类化合物如##STR1##可作为抗血管紧张素II受体拮抗剂。这些化合物在治疗高血压和充血性心力衰竭方面具有活性。
• Treatment of congestive heart failure with angiotensin 11 receptor
  申请人：E. I. Du Pont de Nemours and Company

  公开号：US05128355A1

  公开（公告）日：1992-07-07

  Substituted imidazoles such as ##STR1## are useful as angiotensin II blockers. These compounds have activity in treating hypertension and congestive heart failure.

  取代咪唑类化合物如##STR1##对抗高血压和充血性心力衰竭有一定的活性。
• Amino acid derivatives with angiotensin II antagonist properties
  申请人：Warner-Lambert Company

  公开号：US05041552A1

  公开（公告）日：1991-08-20

  This invention relates to novel amino acid derivatives which antagonize the binding of angiotensin II to its receptors. The compounds are useful in the treatment of hypertension, heart failure, glaucoma, and hyperaldosteronism. Methods of making the compounds, novel intermediates useful in the separation of the compounds, compositions containing the compounds and methods of using them are also covered.

  这项发明涉及新型氨基酸衍生物，其拮抗血管紧张素II与其受体的结合。这些化合物在治疗高血压、心力衰竭、青光眼和高醛固酮症方面具有用途。制备这些化合物的方法，用于分离这些化合物的新型中间体，含有这些化合物的组合物以及使用它们的方法也被涵盖。
• Anilide derivatives with angiotensin II antagonist properties
  申请人：Warner-Lambert Company

  公开号：US05242939A1

  公开（公告）日：1993-09-07

  This invention relates to anilide derivatives of Formula I ##STR1## which antagonize the binding of angiotensin II to its receptors. The compounds are useful in the treatment of hypertension, heart failure, glaucoma, and hyperaldosteronism. Methods of making the compounds, novel intermediates useful in the preparation of the compounds, compositions containing the compounds and methods of using them are also covered.

  这项发明涉及公式I的苯酰胺衍生物，其对抗血管紧张素II与其受体的结合。这些化合物在治疗高血压、心力衰竭、青光眼和高醛固酮血症方面具有用途。制备这些化合物的方法，制备这些化合物的新型中间体，含有这些化合物的组合物以及使用它们的方法也涵盖在内。