6-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-2-methyl-2,6-diazatricyclo[6.3.1.04,12]dodeca-1(11),3,8(12),9-tetraen-7-one | 1263472-64-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 6-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-2-methyl-2,6-diazatricyclo[6.3.1.04,12]dodeca-1(11),3,8(12),9-tetraen-7-one
• CAS: 1263472-64-5
• 化学式: C₁₈H₂₁N₃O
• 分子量: 295.384
• InChiKey: RZKMGDNFMYZIER-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  28.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  (R)-1-methyl-3-((quinuclidin-3-ylamino)methyl)-1H-indole-4-carboxylic acid 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 6-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-2-methyl-2,6-diazatricyclo[6.3.1.04,12]dodeca-1(11),3,8(12),9-tetraen-7-one
  参考文献：
  名称：

  Novel serotonin type 3 receptor partial agonists for the potential treatment of irritable bowel syndrome

  摘要：

  Serotonin type 3 (5-HT(3)) receptor partial agonists are being targeted as potential new drugs for the treatment of irritable bowel syndrome (IBS). Two new chemical series bearing indazole and indole cores have exhibited nanomolar binding affinity for the h5-HT(3)A receptor. A range of partial agonist activities in HEK cells heterologously expressing the h5-HT(3)A receptor were measured for the indazole series. Excellent 5-HT(3) receptor selectivity, favorable in vitro metabolic stability and CYP inhibition properties, and good oral in vivo potency in the murine von Bezold-Jarisch reflex model is exemplified thereby indicating the series to have potential utility as improved IBS agents. (C) 2010 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2010.11.080

文献信息

• Novel serotonin type 3 receptor partial agonists for the potential treatment of irritable bowel syndrome
  作者：David D. Manning、Christopher L. Cioffi、Alexander Usyatinsky、Kevin Fitzpatrick、Liaqat Masih、Cheng Guo、Zhenjun Zhang、Sok Hui Choo、M. Inthikhab Sikkander、Kristen N. Ryan、Jennifer Naginskaya、Carla Hassler、Svetlana Dobritsa、Jonathan D. Wierschke、William G. Earley、Amy S. Butler、Catherine A. Brady、Nicholas M. Barnes、Marlene L. Cohen、Peter R. Guzzo

  DOI：10.1016/j.bmcl.2010.11.080

  日期：2011.1

  Serotonin type 3 (5-HT(3)) receptor partial agonists are being targeted as potential new drugs for the treatment of irritable bowel syndrome (IBS). Two new chemical series bearing indazole and indole cores have exhibited nanomolar binding affinity for the h5-HT(3)A receptor. A range of partial agonist activities in HEK cells heterologously expressing the h5-HT(3)A receptor were measured for the indazole series. Excellent 5-HT(3) receptor selectivity, favorable in vitro metabolic stability and CYP inhibition properties, and good oral in vivo potency in the murine von Bezold-Jarisch reflex model is exemplified thereby indicating the series to have potential utility as improved IBS agents. (C) 2010 Published by Elsevier Ltd.