3α-(4-chloro-3-methylphenyl)tropane-2β-carboxylic acid methyl ester | 1257085-44-1

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 英文名称: 3α-(4-chloro-3-methylphenyl)tropane-2β-carboxylic acid methyl ester
• 英文别名: methyl (1R,2S,3R,5S)-3-(4-chloro-3-methylphenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate
• CAS: 1257085-44-1
• 化学式: C₁₇H₂₂ClNO₂
• 分子量: 307.82
• InChiKey: VMITZEMDDZVHBZ-UGQVUOCMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3α-(4-chloro-3-methylphenyl)tropane-2β-carboxylic acid methyl ester 、 对甲苯磺酸 以 乙酸乙酯 为溶剂， 以1.25 g的产率得到3α-(4-chloro-3-methylphenyl)tropane-2β-carboxylic acid methyl ester tosylate
  参考文献：
  名称：

  Nicotinic Acetylcholine Receptor Efficacy and Pharmacological Properties of 3-(Substituted phenyl)-2β-substituted Tropanes

  摘要：

  There is a need for different and better aids to tobacco product use cessation. Useful smoking cessation aids, bupropion (2) and varenicline (3), share some chemical features with 3-phenyltropanes (4), which have promise in cocaine dependence therapy. Here we report studies to generate and characterize pharmacodynamic features of 3-phenyltropane analogues. These studies extend our work on the multiple molecular target model for aids to smoking cessation. We identified several new 3-phenyltropane analogues that are superior to 2 in inhibition of dopamine, norepinephrine, and sometimes serotonin reuptake. All of these ligands also act as inhibitors of nicotinic acetylcholine receptor (nAChR) function with a selectivity profile that favors, like 2, inhibition of alpha 3 beta 4*-nAChR. Many of these ligands also block acute effects of nicotine-induced antinociception, locomotor activity, and hypothermia. Importantly, all except one of the analogues tested have better potencies in inhibition of nicotine conditioned place preference than 2. We have identified new compounds that have utility as research tools and possible promise for treatment of nicotine dependence.

  DOI：

  10.1021/jm100994w
• 作为产物：
  描述：

  甲醇 、 3α-(4-chloro-3-methylphenyl)-2α-(3'-methyl-1',2',4'-oxadiazol-5-yl)tropane 在 盐酸 、 sodium tetrahydroborate 、 nickel diacetate 作用下， 反应 17.0h， 以0.92 g的产率得到3α-(4-chloro-3-methylphenyl)tropane-2β-carboxylic acid methyl ester
  参考文献：
  名称：

  Nicotinic Acetylcholine Receptor Efficacy and Pharmacological Properties of 3-(Substituted phenyl)-2β-substituted Tropanes

  摘要：

  There is a need for different and better aids to tobacco product use cessation. Useful smoking cessation aids, bupropion (2) and varenicline (3), share some chemical features with 3-phenyltropanes (4), which have promise in cocaine dependence therapy. Here we report studies to generate and characterize pharmacodynamic features of 3-phenyltropane analogues. These studies extend our work on the multiple molecular target model for aids to smoking cessation. We identified several new 3-phenyltropane analogues that are superior to 2 in inhibition of dopamine, norepinephrine, and sometimes serotonin reuptake. All of these ligands also act as inhibitors of nicotinic acetylcholine receptor (nAChR) function with a selectivity profile that favors, like 2, inhibition of alpha 3 beta 4*-nAChR. Many of these ligands also block acute effects of nicotine-induced antinociception, locomotor activity, and hypothermia. Importantly, all except one of the analogues tested have better potencies in inhibition of nicotine conditioned place preference than 2. We have identified new compounds that have utility as research tools and possible promise for treatment of nicotine dependence.

  DOI：

  10.1021/jm100994w

文献信息

• Nicotinic Acetylcholine Receptor Efficacy and Pharmacological Properties of 3-(Substituted phenyl)-2β-substituted Tropanes
  作者：F. Ivy Carroll、Bruce E. Blough、S. Wayne Mascarella、Hernán A. Navarro、J. Brek Eaton、Ronald, J. Lukas、M. Imad Damaj

  DOI：10.1021/jm100994w

  日期：2010.12.9

  There is a need for different and better aids to tobacco product use cessation. Useful smoking cessation aids, bupropion (2) and varenicline (3), share some chemical features with 3-phenyltropanes (4), which have promise in cocaine dependence therapy. Here we report studies to generate and characterize pharmacodynamic features of 3-phenyltropane analogues. These studies extend our work on the multiple molecular target model for aids to smoking cessation. We identified several new 3-phenyltropane analogues that are superior to 2 in inhibition of dopamine, norepinephrine, and sometimes serotonin reuptake. All of these ligands also act as inhibitors of nicotinic acetylcholine receptor (nAChR) function with a selectivity profile that favors, like 2, inhibition of alpha 3 beta 4*-nAChR. Many of these ligands also block acute effects of nicotine-induced antinociception, locomotor activity, and hypothermia. Importantly, all except one of the analogues tested have better potencies in inhibition of nicotine conditioned place preference than 2. We have identified new compounds that have utility as research tools and possible promise for treatment of nicotine dependence.