Imidazole-1-carboxylic acid 2-[1-(3,5-diisopropoxy-phenyl)-3-ethyl-7-methoxy-isoquinolin-6-yloxy]-ethyl ester | 368445-20-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: Imidazole-1-carboxylic acid 2-[1-(3,5-diisopropoxy-phenyl)-3-ethyl-7-methoxy-isoquinolin-6-yloxy]-ethyl ester
• CAS: 368445-20-9
• 化学式: C₃₀H₃₅N₃O₆
• 分子量: 533.624
• InChiKey: JUIRKYNKDKHNKH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.31
• 重原子数：
  39.0
• 可旋转键数：
  11.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  93.93
• 氢给体数：
  0.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  左布地奈德 、 Imidazole-1-carboxylic acid 2-[1-(3,5-diisopropoxy-phenyl)-3-ethyl-7-methoxy-isoquinolin-6-yloxy]-ethyl ester 以 二氯甲烷 为溶剂， 反应 48.0h， 以72%的产率得到carbonic acid 2-[1-(3,5-bis(1-methylethoxy)phenyl)-3-ethyl-7-methoxyisoquinolin-6-yloxy]ethyl ester 2-(5-hydroxy-4a,6a-dimethyl-2-oxo-8-propyl-2,4a,4b,5,6,6a,9a,10,10a,11,12-dodecahydro-7,9-dioxapentaleno[2,1-a]phenanthren-6b-yl)-2-oxo-ethyl ester
  参考文献：
  名称：

  Disease activated drugs: a new concept for the treatment of asthma

  摘要：

  Disease activated drugs (DAD) are pro-drugs of one active principle or combinations of two drugs. which have a proven efficacy for the treatment of the target disease. In opposition to pro-drugs, DAD are activated in inflamed but not normal tissues. Due to the disease specific activation, the amount of locally released drug(s) should be related directly to the severity of the inflammation. To test this concept in asthma a PDE4 inhibitor, an isoquinoline derivative, was chemically derivatized into prodrugs or combined with corticosteroids. These new compounds were more readily cleaved into active PDE4 inhibitor, in bronchoalveolar lavage fluid (BALF) from Brown-Norway rats with lung inflammation than in BALF from rats without airway inflammation. The DAD concept (local selective release and improved therapeutic window) was validated in vivo using the inhibition of methacholine induced bronchoconstriction in guinea pigs with or without ozone induced lung inflammation. An example of DAD hydrolysis (isoquinoline-dexamethasone) was also examined in BALF from asthmatics and healthy volunteers. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00077-3
• 作为产物：
  描述：

  N,N'-羰基二咪唑 、 2-[1-[3,5-Di(propan-2-yloxy)phenyl]-3-ethyl-7-methoxyisoquinolin-6-yl]oxyethanol 在 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 生成 Imidazole-1-carboxylic acid 2-[1-(3,5-diisopropoxy-phenyl)-3-ethyl-7-methoxy-isoquinolin-6-yloxy]-ethyl ester
  参考文献：
  名称：

  Disease activated drugs: a new concept for the treatment of asthma

  摘要：

  Disease activated drugs (DAD) are pro-drugs of one active principle or combinations of two drugs. which have a proven efficacy for the treatment of the target disease. In opposition to pro-drugs, DAD are activated in inflamed but not normal tissues. Due to the disease specific activation, the amount of locally released drug(s) should be related directly to the severity of the inflammation. To test this concept in asthma a PDE4 inhibitor, an isoquinoline derivative, was chemically derivatized into prodrugs or combined with corticosteroids. These new compounds were more readily cleaved into active PDE4 inhibitor, in bronchoalveolar lavage fluid (BALF) from Brown-Norway rats with lung inflammation than in BALF from rats without airway inflammation. The DAD concept (local selective release and improved therapeutic window) was validated in vivo using the inhibition of methacholine induced bronchoconstriction in guinea pigs with or without ozone induced lung inflammation. An example of DAD hydrolysis (isoquinoline-dexamethasone) was also examined in BALF from asthmatics and healthy volunteers. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00077-3