(S)-2β-carbomethoxy-3α-(ethylphenylmethoxy)tropane

• 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: (S)-2β-carbomethoxy-3α-(ethylphenylmethoxy)tropane
• 英文别名: methyl (1S,2S,3S,5R)-8-methyl-3-(1-phenylpropoxy)-8-azabicyclo[3.2.1]octane-2-carboxylate
• 化学式: C₁₉H₂₇NO₃
• 分子量: 317.428
• InChiKey: YVTLPBYWTMWEPR-JCWLEJLNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-苯丙醇 、 (S)-alloecgonine methyl ester 在 对甲苯磺酸 作用下， 以 苯 为溶剂， 反应 18.0h， 以14%的产率得到(S)-2β-carbomethoxy-3α-(ethylphenylmethoxy)tropane
  参考文献：
  名称：

  2-Carbomethoxy-3-(diarylmethoxy)-1αH,5αH-tropane Analogs:  Synthesis and Inhibition of Binding at the Dopamine Transporter and Comparison with Piperazines of the GBR Series

  摘要：

  We recently reported a new class of tropanes, based on benztropine, that bind uniquely, in the S-configuration, to the dopamine transporter. We have now extended this series to evaluate the effects of substituents on the nitrogen and the diarylmethoxy group. Herein we have described the synthesis and biological evaluation of a series of 2-carbomethoxy-3-( diarylmethoxy)-1 alpha H,5 alpha H-tropane (2-carbomethoxybenztropine) analogs. Examination of the binding data obtained for these compounds shows that while the 4,4'-difluoro compound is potent and selective for the dopamine transporter, introduction of larger groups such as 4,4'-dichloro, 4,4'dibromo, 4,4'-diiodo, or 4,4'-dimethyl on the 3-diphenylmethoxy moiety reduces this potency. However, although introduction of only one group (e.g., 4-chloro, 4-bromo, 4-iodo, or 4-methyl) leads to a similar reduction of binding affinity, these monosubstituted 2-carbomethoxybenztropines are significantly more potent than the related disubstituted compounds. Finally, from the data for the N-substituted 2-carbomethoxybenztropine analogs, it is evident that steric bulk can be tolerated at the nitrogen site. A comparison of structure-activity relationship data for the tropanes, GBR analogs, and these benztropines indicates that the 8-carbomethoxybenztropine analogs may be more like the GBR analogs in their mode of binding to the dopamine transporter than like the tropanes. This conclusion supports the notion that the binding site for (-)-cocaine [and the (1R)-tropanes] may differ from that of the 2-carbomethoxybenztropine analogs.

  DOI：

  10.1021/jm950463t

文献信息

• 2-Carbomethoxy-3-(diarylmethoxy)-1α<i>H</i>,5α<i>H</i>-tropane Analogs:  Synthesis and Inhibition of Binding at the Dopamine Transporter and Comparison with Piperazines of the GBR Series
  作者：Peter C. Meltzer、Anna Y. Liang、Bertha K. Madras

  DOI：10.1021/jm950463t

  日期：1996.1.1

  We recently reported a new class of tropanes, based on benztropine, that bind uniquely, in the S-configuration, to the dopamine transporter. We have now extended this series to evaluate the effects of substituents on the nitrogen and the diarylmethoxy group. Herein we have described the synthesis and biological evaluation of a series of 2-carbomethoxy-3-( diarylmethoxy)-1 alpha H,5 alpha H-tropane (2-carbomethoxybenztropine) analogs. Examination of the binding data obtained for these compounds shows that while the 4,4'-difluoro compound is potent and selective for the dopamine transporter, introduction of larger groups such as 4,4'-dichloro, 4,4'dibromo, 4,4'-diiodo, or 4,4'-dimethyl on the 3-diphenylmethoxy moiety reduces this potency. However, although introduction of only one group (e.g., 4-chloro, 4-bromo, 4-iodo, or 4-methyl) leads to a similar reduction of binding affinity, these monosubstituted 2-carbomethoxybenztropines are significantly more potent than the related disubstituted compounds. Finally, from the data for the N-substituted 2-carbomethoxybenztropine analogs, it is evident that steric bulk can be tolerated at the nitrogen site. A comparison of structure-activity relationship data for the tropanes, GBR analogs, and these benztropines indicates that the 8-carbomethoxybenztropine analogs may be more like the GBR analogs in their mode of binding to the dopamine transporter than like the tropanes. This conclusion supports the notion that the binding site for (-)-cocaine [and the (1R)-tropanes] may differ from that of the 2-carbomethoxybenztropine analogs.