4-(4Acetyl-3-hydroxy-2-propylphenoxy)butane nitrile | 92518-31-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(4Acetyl-3-hydroxy-2-propylphenoxy)butane nitrile
• 英文别名: 4-(4-acetyl-3-hydroxy-2-propylphenoxy)butanenitrile
• CAS: 92518-31-5
• 化学式: C₁₅H₁₉NO₃
• 分子量: 261.321
• InChiKey: BGOIQTBSFIIOHE-UHFFFAOYSA-N

物化性质

• 沸点：
  449.5±45.0 °C(Predicted)
• 密度：
  1.109±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  70.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(4Acetyl-3-hydroxy-2-propylphenoxy)butane nitrile 在 sodium azide 、 氯化铵 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 23.0h， 以30%的产率得到1-{2-Hydroxy-3-propyl-4-[3-(5H-tetrazol-5-yl)-propoxy]-phenyl}-ethanone
  参考文献：
  名称：

  Leukotriene receptor antagonists. 1. Synthesis and structure-activity relationships of alkoxyacetophenone derivatives

  摘要：

  A series of derivatives of 2,4-dihydroxy-3-propylacetophenone(1) were prepared and examined for their ability to block leukotriene D4 (LTD4) induced contraction of guinea pig ileum. Straight-chain carboxylic acids where the carboxyl group was separated from the acetophenone moiety by varying numbers of methylenes were evaluated, and maximum activity was obtained with the pentamethylene acid (6). Examination of ring substitution showed that the 2-propyl-3-hydroxy-4-acetyl substitution pattern was required for maximum LTD4 antagonist activity. Additional chain terminal groups were examined, and the acidic 5-tetrazolyl group separated from the acetophenone moiety by four to seven methylenes (26, 23, 27, 28) gave excellent in vitro and in vivo activities. Compound 26 (LY171883) had the best balance of in vitro and in vivo activity. It lacked bronchospastic activity at the doses administered and has been chosen for clinical evaluation.

  DOI：

  10.1021/jm00387a018
• 作为产物：
  描述：

  2,4-二羟基-3-丙基苯乙酮 、 4-氯丁腈 在 potassium carbonate 、 potassium iodide 作用下， 以 丁酮 为溶剂， 反应 72.0h， 以83%的产率得到4-(4Acetyl-3-hydroxy-2-propylphenoxy)butane nitrile
  参考文献：
  名称：

  Leukotriene receptor antagonists. 1. Synthesis and structure-activity relationships of alkoxyacetophenone derivatives

  摘要：

  A series of derivatives of 2,4-dihydroxy-3-propylacetophenone(1) were prepared and examined for their ability to block leukotriene D4 (LTD4) induced contraction of guinea pig ileum. Straight-chain carboxylic acids where the carboxyl group was separated from the acetophenone moiety by varying numbers of methylenes were evaluated, and maximum activity was obtained with the pentamethylene acid (6). Examination of ring substitution showed that the 2-propyl-3-hydroxy-4-acetyl substitution pattern was required for maximum LTD4 antagonist activity. Additional chain terminal groups were examined, and the acidic 5-tetrazolyl group separated from the acetophenone moiety by four to seven methylenes (26, 23, 27, 28) gave excellent in vitro and in vivo activities. Compound 26 (LY171883) had the best balance of in vitro and in vivo activity. It lacked bronchospastic activity at the doses administered and has been chosen for clinical evaluation.

  DOI：

  10.1021/jm00387a018
• 作为试剂：
  描述：

  4-(4-bromobutoxy)-2-hydroxy-3-propylacetophenone 、 sodium cyanide 在 盐酸 、 乙酸乙酯 、 Sodium sulfate-III 、 4-(4Acetyl-3-hydroxy-2-propylphenoxy)butane nitrile 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 以to yield 21.02 g的产率得到4-(4Acetyl-3-hydroxy-2-propylphenoxy)butane nitrile
  参考文献：
  名称：

  Cyano and thiocyano intermediates

  摘要：

  本发明提供了新颖的烷基衍生物，其为白三烯拮抗剂，以及这些衍生物的配方和使用这些衍生物治疗因白三烯过度释放而导致的疾病的方法。

  公开号：

  US04769482A1

文献信息

• MARSHALL W. S.; GOODSON T.; CULLINAN G. J.; SWANSON-BEAN D.; HAISCH K. D.+, J. MED. CHEM., 30,(1987) N 4, 682-689
  作者：MARSHALL W. S.、 GOODSON T.、 CULLINAN G. J.、 SWANSON-BEAN D.、 HAISCH K. D.+

  DOI：——

  日期：——
• US4769482A
  申请人：——

  公开号：US4769482A

  公开（公告）日：1988-09-06
• Leukotriene receptor antagonists. 1. Synthesis and structure-activity relationships of alkoxyacetophenone derivatives
  作者：Winston S. Marshall、Theodore Goodson、George J. Cullinan、Dorothy Swanson-Bean、Klaus D. Haisch、Lynn E. Rinkema、Jerome H. Fleisch

  DOI：10.1021/jm00387a018

  日期：1987.4

  A series of derivatives of 2,4-dihydroxy-3-propylacetophenone(1) were prepared and examined for their ability to block leukotriene D4 (LTD4) induced contraction of guinea pig ileum. Straight-chain carboxylic acids where the carboxyl group was separated from the acetophenone moiety by varying numbers of methylenes were evaluated, and maximum activity was obtained with the pentamethylene acid (6). Examination of ring substitution showed that the 2-propyl-3-hydroxy-4-acetyl substitution pattern was required for maximum LTD4 antagonist activity. Additional chain terminal groups were examined, and the acidic 5-tetrazolyl group separated from the acetophenone moiety by four to seven methylenes (26, 23, 27, 28) gave excellent in vitro and in vivo activities. Compound 26 (LY171883) had the best balance of in vitro and in vivo activity. It lacked bronchospastic activity at the doses administered and has been chosen for clinical evaluation.
• Cyano and thiocyano intermediates
  申请人：Eli Lilly and Company

  公开号：US04769482A1

  公开（公告）日：1988-09-06

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

  本发明提供了新颖的烷基衍生物，其为白三烯拮抗剂，以及这些衍生物的配方和使用这些衍生物治疗因白三烯过度释放而导致的疾病的方法。