(+/-)-2-acetyl-3-(1-piperidinocarbonyl)-7-(N-3,3,3-trifluoropropylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline | 833457-79-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (+/-)-2-acetyl-3-(1-piperidinocarbonyl)-7-(N-3,3,3-trifluoropropylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline
• 英文别名: 2-acetyl-3-(piperidine-1-carbonyl)-N-(3,3,3-trifluoropropyl)-3,4-dihydro-1H-isoquinoline-7-sulfonamide
• CAS: 833457-79-7
• 化学式: C₂₀H₂₆F₃N₃O₄S
• 分子量: 461.505
• InChiKey: FUWSZTQASSBYSF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  95.2
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (+/-)-2-acetyl-3-(1-piperidinocarbonyl)-7-(N-3,3,3-trifluoropropylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline 在 盐酸 作用下， 反应 36.0h， 生成 (+/-)-7-(N-3,3,3-trifluoropropylaminosulfonyl)-1,2,3,4-tetrahydroisoquinolinecarboxylic acid methyl ester
  参考文献：
  名称：

  3-Hydroxymethyl-7-(N-substituted aminosulfonyl)-1,2,3,4-tetrahydroisoquinoline Inhibitors of Phenylethanolamine N-Methyltransferase that Display Remarkable Potency and Selectivity

  摘要：

  Six 3-hydroxymethyl-7-(N-substituted aminosulfonyl)-1,2,3,4-tetrahydroisoquinolines (16-21) were synthesized and evaluated for their phenylethanolamine N-methyltransferase (PNMT) inhibitory potency and affinity for the alpha(2)-adrenoceptor. The addition of nonpolar substituents to the sulfonamide nitrogen of 9 (3-CH2OH-7-SO2NH2-THIQ) led to inhibitors (16-21) that have high PNMT inhibitory potency and high selectivity, and most of these (16-21) are predicted, on the basis of their calculated log P values, to be able to penetrate the blood-brain barrier. Compounds N-trifluoroethyl sulfonamide 20 (PNMT K-i = 23 nM) and N-trifluoropropyl sulfonamide 21 (PNMT Ki = 28 nM) are twice as potent at inhibiting PNMT compared to 9 and display excellent selectivity (alpha(2) K-i/PNMT K-i greater than or equal to 15 000).

  DOI：

  10.1021/jm049368n
• 作为产物：
  描述：

  1,2,3,4-四氢-3-异喹啉羧酸 盐酸盐 在 N-甲基吗啉 、 吡啶 、 氯磺酸 、 sodium hydroxide 、 碳酸氢钠 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 1-羟基苯并三唑 作用下， 以 二氯甲烷 、 乙酸乙酯 、 丙酮 为溶剂， 反应 13.0h， 生成 (+/-)-2-acetyl-3-(1-piperidinocarbonyl)-7-(N-3,3,3-trifluoropropylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  3-Hydroxymethyl-7-(N-substituted aminosulfonyl)-1,2,3,4-tetrahydroisoquinoline Inhibitors of Phenylethanolamine N-Methyltransferase that Display Remarkable Potency and Selectivity

  摘要：

  Six 3-hydroxymethyl-7-(N-substituted aminosulfonyl)-1,2,3,4-tetrahydroisoquinolines (16-21) were synthesized and evaluated for their phenylethanolamine N-methyltransferase (PNMT) inhibitory potency and affinity for the alpha(2)-adrenoceptor. The addition of nonpolar substituents to the sulfonamide nitrogen of 9 (3-CH2OH-7-SO2NH2-THIQ) led to inhibitors (16-21) that have high PNMT inhibitory potency and high selectivity, and most of these (16-21) are predicted, on the basis of their calculated log P values, to be able to penetrate the blood-brain barrier. Compounds N-trifluoroethyl sulfonamide 20 (PNMT K-i = 23 nM) and N-trifluoropropyl sulfonamide 21 (PNMT Ki = 28 nM) are twice as potent at inhibiting PNMT compared to 9 and display excellent selectivity (alpha(2) K-i/PNMT K-i greater than or equal to 15 000).

  DOI：

  10.1021/jm049368n

文献信息

• 3-Hydroxymethyl-7-(<i>N</i>-substituted aminosulfonyl)-1,2,3,4-tetrahydroisoquinoline Inhibitors of Phenylethanolamine <i>N</i>-Methyltransferase that Display Remarkable Potency and Selectivity
  作者：Gary L. Grunewald、F. Anthony Romero、Kevin R. Criscione

  DOI：10.1021/jm049368n

  日期：2005.1.1

  Six 3-hydroxymethyl-7-(N-substituted aminosulfonyl)-1,2,3,4-tetrahydroisoquinolines (16-21) were synthesized and evaluated for their phenylethanolamine N-methyltransferase (PNMT) inhibitory potency and affinity for the alpha(2)-adrenoceptor. The addition of nonpolar substituents to the sulfonamide nitrogen of 9 (3-CH2OH-7-SO2NH2-THIQ) led to inhibitors (16-21) that have high PNMT inhibitory potency and high selectivity, and most of these (16-21) are predicted, on the basis of their calculated log P values, to be able to penetrate the blood-brain barrier. Compounds N-trifluoroethyl sulfonamide 20 (PNMT K-i = 23 nM) and N-trifluoropropyl sulfonamide 21 (PNMT Ki = 28 nM) are twice as potent at inhibiting PNMT compared to 9 and display excellent selectivity (alpha(2) K-i/PNMT K-i greater than or equal to 15 000).