(R)-2-(tert-butoxycarbonyl)-7-(methylsulfonamido)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid | 1016163-01-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: (R)-2-(tert-butoxycarbonyl)-7-(methylsulfonamido)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
• CAS: 1016163-01-1
• 化学式: C₁₆H₂₂N₂O₆S
• 分子量: 370.426
• InChiKey: XLTJXZSRKGVGBR-CYBMUJFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  25.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  113.01
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (R)-2-(tert-butoxycarbonyl)-7-(methylsulfonamido)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid 、 3-[1-(2S-amino-3-methylbutyl)-3R,4R-dimethyl-4-piperidinyl]phenol 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 tert-butyl (3R)-3-{[(1S)-1-{[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethylpiperidin-1-yl]methyl}-2-methylpropyl]carbamoyl}-7-[(methylsulfonyl)-amino]-3,4-dihydroisoquinoline-2(1H)carboxylate
  参考文献：
  名称：

  Synthesis and In Vitro Opioid Receptor Functional Antagonism of Analogues of the Selective Kappa Opioid Receptor Antagonist (3R)-7-Hydroxy-N-((1S)-1-{[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl}-2-methylpropyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxamide (JDTic)

  摘要：

  In previous structure-activity relationship (SAR) studies, we identified (3R)-7-hydroxy-N-((1S)-1-{[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl}-2-methylpropyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxamide (JDTic, 1) as the first potent and selective K opioid receptor antagonist from the trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine class of opioid antagonist. In the present study, we report the synthesis and in vitro opioid receptor functional antagonism of a number of analogues of 1 using a [S-35]GTP gamma S binding assay. The results from the studies better define the pharmacophore for this class of K opioid receptor antagonist and has identified new potent and selective kappa antagonist. (3R)-7-Hydroxy-N-[(1 S, 2S)-1-{[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethylpiperidin-1-yl]methyl}-2-methylbutyl]-1,2,3,4tetrahydroisoquinoline-3-carboxamide (3) with a K-e value of 0.03 nM at the kappa receptor and 100- and 793-fold selectivity relative to the mu and delta receptors was the most potent and selective kappa opioid receptor antagonist identified.

  DOI：

  10.1021/jm701344b