8-methyl-6β-(p-nitrobenzoyloxy)-8-azabicyclo[3.2.1]octane

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 8-methyl-6β-(p-nitrobenzoyloxy)-8-azabicyclo[3.2.1]octane
• 英文别名: 6β-(p-nitrobenzoyloxy)tropane；[(1S,5R,6S)-8-methyl-8-azabicyclo[3.2.1]octan-6-yl] 4-nitrobenzoate
• 化学式: C₁₅H₁₈N₂O₄
• 分子量: 290.319
• InChiKey: ABUKEJSHBJAZFH-MJBXVCDLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  75.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  8-methyl-6β-(p-nitrobenzoyloxy)-8-azabicyclo[3.2.1]octane 在 溶剂黄146 、 锌 作用下， 以 甲苯 为溶剂， 反应 48.0h， 生成 6β-(p-nitrobenzoyloxy)nortropane
  参考文献：
  名称：

  6β-Acyloxy(nor)tropanes:  Affinities for Antagonist/Agonist Binding Sites on Transfected and Native Muscarinic Receptors

  摘要：

  A series of esters of 6 beta-hydroxynortropane and the N-methyl analogue 6 beta-tropanol were synthesized and screened versus binding of an antagonist (quinuclidinyl benzilate) and an agonist (oxotremorine-M) at sites on human m(1)-, m(2)-, m(3)-, and m(4)-muscarinic receptors in transfected cell membranes and on native M-1-muscarinic receptors in rat brain membranes and native M-2-muscarinic receptors in rat heart membranes. Most 6 beta-acyloxy(nor)tropanes had higher affinity versus oxotremorine-M binding compared to quinuclidinyl benzilate binding at transfected m(1)- and native M-1-receptors, indicative of agonist activity. 6 beta-Acetoxynortropane had K-i values versus oxotremorine-M binding at m(1)-, m(2)-, and m(4)-receptors ranging from 4 to 7 nM. N-Methylation reduced affinity greatly as did increasing the size of the acyl moiety. The affinity of 6 beta-benzoyloxynortropane and other analogues with larger acyl moieties was little affected by N-methylation or in some cases was increased. 6 beta-Acyloxy(nor)tropanes and classical muscarinic agonists, such as muscarine and oxotremorine, had higher affinity versus oxotremorine-M binding compared to quinuclidinyl benzilate binding at native M-2-muscarinic receptors of heart, but not at transfected m(2)-muscarinic receptors. Antagonist/agonist binding ratios were not obtained for transfected m(3)-receptors, since significant oxotremorine-M binding could not be detected. 6 beta-Acyloxy(nor)tropane, two other (nor)tropanes, and the classical muscarinic agonists had higher affinity versus agonist binding compared to antagonist binding for transfected m(4)-receptors. The antagonist/agonist binding ratio method is clearly not always reliable for predicting agonist activity at muscarinic receptors.

  DOI：

  10.1021/jm9904001
• 作为产物：
  描述：

  4-硝基苯甲酰氯 、 (+/-)-8-methyl-8-azabicyclo[3.2.1]octan-β-ol 在 三乙胺 作用下， 以 乙醚 为溶剂， 以78%的产率得到8-methyl-6β-(p-nitrobenzoyloxy)-8-azabicyclo[3.2.1]octane
  参考文献：
  名称：

  6β-Acyloxy(nor)tropanes:  Affinities for Antagonist/Agonist Binding Sites on Transfected and Native Muscarinic Receptors

  摘要：

  A series of esters of 6 beta-hydroxynortropane and the N-methyl analogue 6 beta-tropanol were synthesized and screened versus binding of an antagonist (quinuclidinyl benzilate) and an agonist (oxotremorine-M) at sites on human m(1)-, m(2)-, m(3)-, and m(4)-muscarinic receptors in transfected cell membranes and on native M-1-muscarinic receptors in rat brain membranes and native M-2-muscarinic receptors in rat heart membranes. Most 6 beta-acyloxy(nor)tropanes had higher affinity versus oxotremorine-M binding compared to quinuclidinyl benzilate binding at transfected m(1)- and native M-1-receptors, indicative of agonist activity. 6 beta-Acetoxynortropane had K-i values versus oxotremorine-M binding at m(1)-, m(2)-, and m(4)-receptors ranging from 4 to 7 nM. N-Methylation reduced affinity greatly as did increasing the size of the acyl moiety. The affinity of 6 beta-benzoyloxynortropane and other analogues with larger acyl moieties was little affected by N-methylation or in some cases was increased. 6 beta-Acyloxy(nor)tropanes and classical muscarinic agonists, such as muscarine and oxotremorine, had higher affinity versus oxotremorine-M binding compared to quinuclidinyl benzilate binding at native M-2-muscarinic receptors of heart, but not at transfected m(2)-muscarinic receptors. Antagonist/agonist binding ratios were not obtained for transfected m(3)-receptors, since significant oxotremorine-M binding could not be detected. 6 beta-Acyloxy(nor)tropane, two other (nor)tropanes, and the classical muscarinic agonists had higher affinity versus agonist binding compared to antagonist binding for transfected m(4)-receptors. The antagonist/agonist binding ratio method is clearly not always reliable for predicting agonist activity at muscarinic receptors.

  DOI：

  10.1021/jm9904001

文献信息

• 6β-Acyloxy(nor)tropanes:  Affinities for Antagonist/Agonist Binding Sites on Transfected and Native Muscarinic Receptors
  作者：John W. Daly、Tara H. Gupta、William L. Padgett、Xue-Feng Pei

  DOI：10.1021/jm9904001

  日期：2000.6.1

  A series of esters of 6 beta-hydroxynortropane and the N-methyl analogue 6 beta-tropanol were synthesized and screened versus binding of an antagonist (quinuclidinyl benzilate) and an agonist (oxotremorine-M) at sites on human m(1)-, m(2)-, m(3)-, and m(4)-muscarinic receptors in transfected cell membranes and on native M-1-muscarinic receptors in rat brain membranes and native M-2-muscarinic receptors in rat heart membranes. Most 6 beta-acyloxy(nor)tropanes had higher affinity versus oxotremorine-M binding compared to quinuclidinyl benzilate binding at transfected m(1)- and native M-1-receptors, indicative of agonist activity. 6 beta-Acetoxynortropane had K-i values versus oxotremorine-M binding at m(1)-, m(2)-, and m(4)-receptors ranging from 4 to 7 nM. N-Methylation reduced affinity greatly as did increasing the size of the acyl moiety. The affinity of 6 beta-benzoyloxynortropane and other analogues with larger acyl moieties was little affected by N-methylation or in some cases was increased. 6 beta-Acyloxy(nor)tropanes and classical muscarinic agonists, such as muscarine and oxotremorine, had higher affinity versus oxotremorine-M binding compared to quinuclidinyl benzilate binding at native M-2-muscarinic receptors of heart, but not at transfected m(2)-muscarinic receptors. Antagonist/agonist binding ratios were not obtained for transfected m(3)-receptors, since significant oxotremorine-M binding could not be detected. 6 beta-Acyloxy(nor)tropane, two other (nor)tropanes, and the classical muscarinic agonists had higher affinity versus agonist binding compared to antagonist binding for transfected m(4)-receptors. The antagonist/agonist binding ratio method is clearly not always reliable for predicting agonist activity at muscarinic receptors.