1-<2-hydroxy-3-propyl-4-<<4-(1H-tetrazol-5-yl)phenoxy>methyl>phenyl>ethanone | 97581-69-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-<2-hydroxy-3-propyl-4-<<4-(1H-tetrazol-5-yl)phenoxy>methyl>phenyl>ethanone
• 英文别名: 5-[4-((4-Acetyl-3-hydroxy-2-propylphenyl)methoxy)phenyl]-1H-tetrazole；5-[4-(4-Acetyl-3-hydroxy-2-propylbenzyloxy)phenyl]-tetrazole；5-[4-(4-Acetyl-3-hydroxy-2-propylbenzyloxy)phenyl]tetrazole；1-[2-hydroxy-3-propyl-4-[[4-(2H-tetrazol-5-yl)phenoxy]methyl]phenyl]ethanone
• CAS: 97581-69-6
• 化学式: C₁₉H₂₀N₄O₃
• 分子量: 352.393
• InChiKey: JTTSKYBQFRJIPS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-<2-hydroxy-3-propyl-4-<<4-(1H-tetrazol-5-yl)phenoxy>methyl>phenyl>ethanone 在 三正丁基叠氮化锡 、 potassium carbonate 作用下， 以 乙二醇二甲醚 、 丙酮 为溶剂， 反应 116.0h， 生成 1-[2-Hydroxy-3-propyl-4-(4-{2-[3-(1H-tetrazol-5-yl)-propyl]-2H-tetrazol-5-yl}-phenoxymethyl)-phenyl]-ethanone
  参考文献：
  名称：

  (Phenylmethoxy)phenyl derivatives of w-oxo- and w-tetrazolylalkanoic acids and related tetrazoles. Synthesis and evaluation as leukotriene D4 receptor antagonists

  摘要：

  Two series of (phenylmethoxy)phenyl compounds derived from the structure of LY163443 were synthesized and evaluated as leukotriene D4 receptor antagonists. In the OMEGA-[(phenylmethoxy)phenyl]-OMEGA-oxoalkanoic acid series, 5-[4-[(4-acetyl-2-ethyl-3-hydroxyphenyl)methoxy]phenyl]-3,3-dimethyl-5-oxopentanoic acid (8) was the most potent antagonist of LTD4-induced contractions of guinea pig ileum (pK(B) of 7.60) and LTD4 pressor response in pithed rats (ED50 of 1.4 mg/kg iv). Replacing the carboxylic acid function with 5-tetrazole gave slightly more potent compounds. In the OMEGA-[5-[[(phenylmethoxy)phenyl]alkyl]tetrazolyl]alkanoic acid series, replacing the carboxylic acid with 5-tetrazole gave compounds that were equally effective in the guinea pig ileum but more potent in vivo against the LTD4 pressor response in rat. The pK(B) value in the guinea pig ileum for 1-[2-hydroxy-3-propyl-4-[[4-[[2-[3-(1H-tetrazol-5-yl)propyl]-2H-tetrazol-5-yl]methyl]phenoxy]methyl]phenyl]ethanone (25) was 7.87 and the ED50 for antagonism of the LTD4 pressor response was 4.0 mg/kg iv. The sodium salts of 8 (9) and 25 (26) given by the iv route of administration antagonized LTD4-induced cardiovascular alterations in anesthetized rat and LTD4-induced bronchoconstriction in guinea pig in a dose-dependent manner. Oral activity was also demonstrated against the LTD4-induced bronchoconstriction in guinea pig.

  DOI：

  10.1021/jm00113a014
• 作为产物：
  描述：

  1-<4-<(dimethylamino)methyl>-2-hydroxy-3-propylphenyl>ethanone 在 sodium azide 、 sodium ethanolate 、 氯甲酸乙酯 、 氯化铵 、 sodium iodide 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 70.25h， 生成 1-<2-hydroxy-3-propyl-4-<<4-(1H-tetrazol-5-yl)phenoxy>methyl>phenyl>ethanone
  参考文献：
  名称：

  白三烯受体拮抗剂。2。[[（四唑-5-基芳基）氧基]甲基]苯乙酮衍生物。

  摘要：

  合成了一系列[[（（四唑-5-基芳基）氧基]甲基]苯乙酮，并作为白三烯D4诱导的豚鼠回肠收缩的拮抗剂进行了评估。在苯乙酮的3-位上用乙基（66），丙基（68），丁基（83）和异丁基（84）取代，得到的-log IC 50值分别为7.9、8.0、7.8和7.7。当四唑-5-基通过化学键（67），亚甲基（68）或乙烯（71）与对位的第二个苯环连接时，会得到同样有效的化合物。为了保持高拮抗剂活性，苯乙酮应在2位上被羟基取代，四唑环应具有酸性氢原子。1- [2-羟基-3-丙基-4-[[4-（1H-四唑-5-基甲基）苯氧基]甲基]苯基]乙酮（68，

  DOI：

  10.1021/jm00388a028

文献信息

• Leukotriene antagonist intermediates
  申请人：Eli Lilly and Company

  公开号：US05105017A1

  公开（公告）日：1992-04-14

  This invention provides novel benzene derivatives which are leukotriene antagonists, formulations of those derivatives, intermediates for preparing the derivatives, and a method of using those derivatives for the treatment of conditions characterized by an excessive release of leukotrienes.

  这项发明提供了新颖的苯乙烯衍生物，它们是白三烯拮抗剂，包括这些衍生物的配方、制备这些衍生物的中间体，以及使用这些衍生物治疗由白三烯过度释放引起的病症的方法。
• Leukotriene antagonists
  申请人：Eli Lilly and Company

  公开号：US05393768A1

  公开（公告）日：1995-02-28

  This invention provides novel benzene derivatives which are leukotriene antagonists, formulations of those derivatives, intermediates for preparing the derivatives, and a method of using those derivatives for the treatment of conditions characterized by an excessive release of leukotrienes.

  本发明提供了新型苯并衍生物，它们是白三烯拮抗剂，这些衍生物的配方、制备这些衍生物的中间体以及使用这些衍生物治疗白三烯过度释放症状的方法。
• DILLARD R. D.; CARR F. P.; MCCULLOUGH D.; HAISCH K. D.; RINKEMA L. E.; FL+, J. MED. CHEM., 30,(1987) N 5, 911-918
  作者：DILLARD R. D.、 CARR F. P.、 MCCULLOUGH D.、 HAISCH K. D.、 RINKEMA L. E.、 FL+

  DOI：——

  日期：——
• US5105017A
  申请人：——

  公开号：US5105017A

  公开（公告）日：1992-04-14
• US5393768A
  申请人：——

  公开号：US5393768A

  公开（公告）日：1995-02-28