1-[4-(9-Bromo-nonyloxy)-2-hydroxy-3-propyl-phenyl]-ethanone | 79557-82-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-[4-(9-Bromo-nonyloxy)-2-hydroxy-3-propyl-phenyl]-ethanone
• 英文别名: 1-[4-(9-Bromononoxy)-2-hydroxy-3-propylphenyl]ethanone
• CAS: 79557-82-7
• 化学式: C₂₀H₃₁BrO₃
• 分子量: 399.368
• InChiKey: VDXRWRDVWGRKCC-UHFFFAOYSA-N

物化性质

• 沸点：
  497.0±45.0 °C(Predicted)
• 密度：
  1.181±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  24
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-[4-(9-Bromo-nonyloxy)-2-hydroxy-3-propyl-phenyl]-ethanone 在 sodium azide 、 氯化铵 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 40.0h， 生成
  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 、 1,9-二溴壬烷 在 potassium carbonate 、 potassium iodide 作用下， 以 丙酮 为溶剂， 反应 18.0h， 以63%的产率得到1-[4-(9-Bromo-nonyloxy)-2-hydroxy-3-propyl-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

文献信息

• Phenol derivatives, processes for their preparation and pharmaceutical compositions containing them
  申请人：GLAXO GROUP LIMITED

  公开号：EP0028063A1

  公开（公告）日：1981-05-06

  Compounds are disclosed which are phenoxyalkoxyphenyl derivatives of general formula (I) wherein Y represents the group -A, -ZA or OZ1A where A represents a carboxylic acid group, a 5-1H-tetrazolyf ring or a N-5-1 H-tetrazolylcarboxamide group; Z represents a Ci-4 alkylene, C2-4 alkenylene or C2-4 alkynylene chain optionally substituted by one or more C1-3 alkyl groups and Z1 represents a C1-4 alkylene chain optionally substituted by one or more C1-3 alkyl groups; X represents a C1-10 carbon chain which may be saturated or unsaturated in the case of chains containing at least 4 carbon atoms, and may be substituted by a hydroxy group or by one or more C1-3 alkyl groups, which chain may be interrupted by a benzene ring which may be linked through its 1- and 2-, 1- and 3-, or 1- and 4-positions; R1 represents a hydrogen atom or a C1-6 alkyl group; R2 represents the group -COR6 where R6 represents a hydrogen atom, an aryl group or a C1-6 alkyl group which may be substituted by an aryl group; R3 represents a C1-6 alkyl group or a C3-6 alkenyl group; and R4 and R5 which may be the same or different, each represents a hydrogen atom, a halogen atom or a hydroxy, Ci-3 alkoxy, C1-6 alkyl, C3-C6 alkenyl, C1-3 alkanoyl, nitro or carboxylic acid group with the proviso that R4 and R5 cannot both be nitro, alkanoyl or carboxylic acid groups, and physologically acceptable salts thereof. The compounds are potent antagonists of the action of slow reacting substance of anaphylaxis and are thus indicated for use in the treatment of obstructive airways diseases such as asthma and hay fever and in skin afflictions.

  所公开的化合物是通式(I)的苯氧基烷氧基苯基衍生物 其中 Y 代表基团-A、-ZA 或 OZ1A，其中 A 代表羧酸基团、5-1H-四氮唑环或 N-5-1 H-四氮唑甲酰胺基团； Z 代表任选被一个或多个 C1-3 烷基取代的 Ci-4亚烷基、C2-4 亚烯基或 C2-4 亚炔基链，Z1 代表任选被一个或多个 C1-3 烷基取代的 C1-4 亚烷基链； X 代表 C1-10 碳链，可以是饱和的 或不饱和（如果链中至少含有 4 个碳原子），并可被羟基取代 或一个或多个 C1-3 烷基基团取代，该链可 可被一个苯环打断，该苯环可通过以下方式连接 1-位和 2-位、1-位和 3-位或 1-位和 4-位相连； R1 代表氢原子或 C1-6 烷基； R2 代表基团-COR6，其中 R6 代表氢原子、芳基或可被芳基取代的 C1-6 烷基； R3 代表 C1-6 烷基或 C3-6 烯基；以及 R4和R5可以相同或不同，各自代表氢原子、卤素原子或羟基、Ci-3烷氧基、C1-6烷基、C3-C6烯基、C1-3烷酰基、硝基或羧酸基团，但R4和R5不能都是硝基、烷酰基或羧酸基团，以及它们的物理上可接受的盐。 这些化合物是过敏性休克慢反应物质的强效拮抗剂，因此可用于治疗阻塞性呼吸道疾病，如哮喘和花粉症，以及皮肤病。
• 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：——
• 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.