8-(4-Oxo-1-phenyl-1,3,8-triaza-spiro[4.5]dec-8-ylmethyl)-7,8-dihydro-3H-6,9-dioxa-3-aza-cyclopenta[a]naphthalene-2-carboxylic acid benzyl ester | 137578-28-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 8-(4-Oxo-1-phenyl-1,3,8-triaza-spiro[4.5]dec-8-ylmethyl)-7,8-dihydro-3H-6,9-dioxa-3-aza-cyclopenta[a]naphthalene-2-carboxylic acid benzyl ester
• 英文别名: benzyl 2-[(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)methyl]-3,7-dihydro-2H-[1,4]dioxino[2,3-e]indole-8-carboxylate
• CAS: 137578-28-0
• 化学式: C₃₂H₃₂N₄O₅
• 分子量: 552.63
• InChiKey: DQQCWQGYIUCCKR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  41
• 可旋转键数：
  7
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  96.1
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-(oxiranylmethoxy)-2-(phenylmethoxy)benzaldehyde 在 palladium on activated charcoal 4-二甲氨基吡啶 、 3 A molecular sieve 、 四丁基氟化铵 、 sodium methylate 、 potassium carbonate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 环己烯 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 二氯甲烷 、 甲苯 、 xylene 为溶剂， 反应 48.5h， 生成 8-(4-Oxo-1-phenyl-1,3,8-triaza-spiro[4.5]dec-8-ylmethyl)-7,8-dihydro-3H-6,9-dioxa-3-aza-cyclopenta[a]naphthalene-2-carboxylic acid benzyl ester
  参考文献：
  名称：

  Novel indolodioxanes with antihypertensive effects: potent ligands for the 5-HT1A receptor

  摘要：

  The synthesis and biological evaluation of a new family of tricyclic indolodioxanes is described. These compounds all contain the 2,3-dihydro-7H-1,4-dioxino[2,3-e]indole nucleus and bear substituents at the 2 and/or 8 positions. Thirteen members of this class were prepared and shown to be potent ligands for the 5-HTA receptor, with several compounds displaying subnanomolar inhibition constants. These compounds also bind to the dopamine D-2 receptor, but generally with higher inhibition constants than those for 5-HT1A. Certain members of this novel structural class show in vivo activity in the mouse hypothermia assay. One of these compounds, U-86192A, has been shown to have antihypertensive effects in the cat, completely eliminating sympathetic nerve discharge at 1 mg/kg iv and lowering mean arterial pressure to 50% pretreatment levels. These effects can be reversed by the administration of spiperone, indicating that U-86192A is acting via a central serotonergic mechanism.

  DOI：

  10.1021/jm00094a021

文献信息

• Novel indolodioxanes with antihypertensive effects: potent ligands for the 5-HT1A receptor
  作者：Michael D. Ennis、Mark E. Baze、Martin W. Smith、Charles F. Lawson、Robert B. McCall、Robert A. Lahti、Montford F. Piercey

  DOI：10.1021/jm00094a021

  日期：1992.8

  The synthesis and biological evaluation of a new family of tricyclic indolodioxanes is described. These compounds all contain the 2,3-dihydro-7H-1,4-dioxino[2,3-e]indole nucleus and bear substituents at the 2 and/or 8 positions. Thirteen members of this class were prepared and shown to be potent ligands for the 5-HTA receptor, with several compounds displaying subnanomolar inhibition constants. These compounds also bind to the dopamine D-2 receptor, but generally with higher inhibition constants than those for 5-HT1A. Certain members of this novel structural class show in vivo activity in the mouse hypothermia assay. One of these compounds, U-86192A, has been shown to have antihypertensive effects in the cat, completely eliminating sympathetic nerve discharge at 1 mg/kg iv and lowering mean arterial pressure to 50% pretreatment levels. These effects can be reversed by the administration of spiperone, indicating that U-86192A is acting via a central serotonergic mechanism.