3β-(4-ethylthiophenyl)tropane-2β-carboxylic acid methyl ester | 1186233-79-3

• 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: 3β-(4-ethylthiophenyl)tropane-2β-carboxylic acid methyl ester
• CAS: 1186233-79-3
• 化学式: C₁₈H₂₅NO₂S
• 分子量: 319.468
• InChiKey: BYRGPNIGCQCEQB-SVGFKBNWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.54
• 重原子数：
  22.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  29.54
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  3β-(4-ethylthiophenyl)tropane-2β-carboxylic acid methyl ester 在 盐酸 作用下， 生成 3β-(4-ethylthiophenyl)tropane-2β-carboxylic acid methyl ester hydrochloride
  参考文献：
  名称：

  Synthesis and structure–activity relationship of 3β-(4-alkylthio, -methylsulfinyl, and -methylsulfonylphenyl)tropane and 3β-(4-alkylthiophenyl)nortropane derivatives for monoamine transporters

  摘要：

  Early studies led to the identification of 3 beta-(4-methoxyphenyl)tropane-2 beta-carboxylic acid methyl ester (5) with high affinity at the DAT (IC(50) = 6.5 nM) and 5-HTT (K(i) = 4.3 nM), while having much less affinity at the NET (K(i) = 1110 nM). In the present study, we replaced the 4'-methoxy group of the 3 beta-phenyl ring with a bioisosteric 4'-methylthio group to give 7a. We also synthesized a number of 3 beta-(4-alkylthiophenyl)tropanes 7b-e, 3 beta-(4-methylsulfinylphenyl) and 3 beta-(4-methylsulfonylphenyl)tropane analogues 7f-h as well as the 3 beta-(4-alkylthiophenyl)nortropane derivatives 8-11 to further characterize the structure-activity relationship of this type of compound for binding at monoamine transporters. With exception of the 4'-methylsulfonyl analogue 7h, all the tested compounds possessed high binding affinities at the 5-HTT. The K(i) values ranged from 0.19 nM to 49 nM. The 3 beta-(4-methylthiophenyl)tropane 7a and its N-(3-fluoropropyl) analogue 9a and N- allyl analogue 10a are the most selective compounds for the 5-HTT over the NET (NET/5-HTT = 314-364) in the series. However, none of the compounds showed selectivity similar to 5 for both the DAT and 5-HTT relative to the NET. This study provided useful SAR information for rational design of potent and selective monoamine transporter inhibitors. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.05.052
• 作为产物：
  描述：

  1-溴-4-(乙基硫代)苯 、 脱水芽子碱甲基酯甲磺酸盐 在 碘 、 magnesium 、 1,2-二溴乙烷 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 1.5h， 以62%的产率得到3β-(4-ethylthiophenyl)tropane-2β-carboxylic acid methyl ester
  参考文献：
  名称：

  Synthesis and structure–activity relationship of 3β-(4-alkylthio, -methylsulfinyl, and -methylsulfonylphenyl)tropane and 3β-(4-alkylthiophenyl)nortropane derivatives for monoamine transporters

  摘要：

  Early studies led to the identification of 3 beta-(4-methoxyphenyl)tropane-2 beta-carboxylic acid methyl ester (5) with high affinity at the DAT (IC(50) = 6.5 nM) and 5-HTT (K(i) = 4.3 nM), while having much less affinity at the NET (K(i) = 1110 nM). In the present study, we replaced the 4'-methoxy group of the 3 beta-phenyl ring with a bioisosteric 4'-methylthio group to give 7a. We also synthesized a number of 3 beta-(4-alkylthiophenyl)tropanes 7b-e, 3 beta-(4-methylsulfinylphenyl) and 3 beta-(4-methylsulfonylphenyl)tropane analogues 7f-h as well as the 3 beta-(4-alkylthiophenyl)nortropane derivatives 8-11 to further characterize the structure-activity relationship of this type of compound for binding at monoamine transporters. With exception of the 4'-methylsulfonyl analogue 7h, all the tested compounds possessed high binding affinities at the 5-HTT. The K(i) values ranged from 0.19 nM to 49 nM. The 3 beta-(4-methylthiophenyl)tropane 7a and its N-(3-fluoropropyl) analogue 9a and N- allyl analogue 10a are the most selective compounds for the 5-HTT over the NET (NET/5-HTT = 314-364) in the series. However, none of the compounds showed selectivity similar to 5 for both the DAT and 5-HTT relative to the NET. This study provided useful SAR information for rational design of potent and selective monoamine transporter inhibitors. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.05.052