N-<3-<3,4-bis(benzyloxy)phenyl>propyl>-3,4,5-trimethoyphenylacetamide | 99281-98-8

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 石蒜科生物碱
• 英文名称: N-<3-<3,4-bis(benzyloxy)phenyl>propyl>-3,4,5-trimethoyphenylacetamide
• 英文别名: N-[3-(3,4-bis(benzyloxy)phenyl)propyl]-3,4,5-trimethoyphenylacetamide
• CAS: 99281-98-8
• 化学式: C₃₄H₃₇NO₆
• 分子量: 555.671
• InChiKey: TWSBRYKPLWGUIR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.16
• 重原子数：
  41.0
• 可旋转键数：
  15.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  75.25
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  N-<3-<3,4-bis(benzyloxy)phenyl>propyl>-3,4,5-trimethoyphenylacetamide 在 palladium on activated charcoal 硼烷四氢呋喃络合物 、 氢气 、 三氯氧磷 作用下， 以 四氢呋喃 、 乙醇 、 乙腈 为溶剂， 25.0 ℃ 、275.79 kPa 条件下， 反应 5.0h， 生成 1-[(3,4,5-trimethoxyphenyl)methyl]-7,8-dihydroxy-2,3,4,5-tetrhydro-1H-2-benzazepine
  参考文献：
  名称：

  Synthesis and investigation of the .alpha.-adrenoceptor agonist and platelet antiaggregatory properties of 1,7,8-trisubstituted 2,3,4,5-tetrahydro-1H-2-benzazepine analogs of trimetoquinol

  摘要：

  The synthesis and biological evaluation of 7,8-dihydroxy (2) and 7,8-methylenedioxy (3) analogues of 1-[(3,4,5-trimethyoxyphenyl)methyl]-2,3,4,5-tetradhyo-1H-2-b enzazepine on beta-adrenoceptor systems and human platelets were undertaken and compared with trimetoquinol (TMQ, 1). Whereas 1 is a potent beta-adrenoceptor agonist in guinea pig atria and trachea (pD2 = 8.2), analogue 2 was marginally effective at relaxing guinea pig tracheal smooth muscle (pD2 = 4.4) and inactive as an agonist on guinea pig atria. Analogues 2 and 3 were inhibitors of phospholipase C (PLC; from Clostridium perfringens) induced and secondary wave of ADP-induced aggregation responses and inactive against low-dose thrombin-induced or stable endoperoxide (U46619) induced human platelet aggregation. Against ADP-induced serotonin secretion, 3 was 9-fold more active than analogue 2. Further, the rank order of TMQ isomers and 3 as inhibitors of PLC-induced platelet aggregation, serotonin secretion, and phosphatidylinositol degradation was identical (3 greater than (S)-(-)-1 greater than (R)-(+)-1). The results suggest that these compounds are blocking the action of PLC by interfering with phosphatidylinositol turnover in platelet membranes. The inhibition of ADP-induced responses in human platelets by analogues 2 and 3 also suggests a site of inhibition at a level of arachidonic acid release. Thus, ring expansion of 1 as in the benzazepine analogues 2 and 3 has allowed us to develop selective inhibitors of platelet function that lack significant beta-adrenoceptor activity.

  DOI：

  10.1021/jm00152a003
• 作为产物：
  描述：

  3,4,5-三甲氧基苯乙酸 、 3-<3,4-bis(benzyloxy)phenyl>-1-aminopropane 以 甲苯 为溶剂， 反应 72.0h， 以61%的产率得到N-<3-<3,4-bis(benzyloxy)phenyl>propyl>-3,4,5-trimethoyphenylacetamide
  参考文献：
  名称：

  Synthesis and investigation of the .alpha.-adrenoceptor agonist and platelet antiaggregatory properties of 1,7,8-trisubstituted 2,3,4,5-tetrahydro-1H-2-benzazepine analogs of trimetoquinol

  摘要：

  The synthesis and biological evaluation of 7,8-dihydroxy (2) and 7,8-methylenedioxy (3) analogues of 1-[(3,4,5-trimethyoxyphenyl)methyl]-2,3,4,5-tetradhyo-1H-2-b enzazepine on beta-adrenoceptor systems and human platelets were undertaken and compared with trimetoquinol (TMQ, 1). Whereas 1 is a potent beta-adrenoceptor agonist in guinea pig atria and trachea (pD2 = 8.2), analogue 2 was marginally effective at relaxing guinea pig tracheal smooth muscle (pD2 = 4.4) and inactive as an agonist on guinea pig atria. Analogues 2 and 3 were inhibitors of phospholipase C (PLC; from Clostridium perfringens) induced and secondary wave of ADP-induced aggregation responses and inactive against low-dose thrombin-induced or stable endoperoxide (U46619) induced human platelet aggregation. Against ADP-induced serotonin secretion, 3 was 9-fold more active than analogue 2. Further, the rank order of TMQ isomers and 3 as inhibitors of PLC-induced platelet aggregation, serotonin secretion, and phosphatidylinositol degradation was identical (3 greater than (S)-(-)-1 greater than (R)-(+)-1). The results suggest that these compounds are blocking the action of PLC by interfering with phosphatidylinositol turnover in platelet membranes. The inhibition of ADP-induced responses in human platelets by analogues 2 and 3 also suggests a site of inhibition at a level of arachidonic acid release. Thus, ring expansion of 1 as in the benzazepine analogues 2 and 3 has allowed us to develop selective inhibitors of platelet function that lack significant beta-adrenoceptor activity.

  DOI：

  10.1021/jm00152a003