1-tert-butoxycarbonyl-(3R,4R)-dimethyl-4-(3-benzyloxyphenyl)piperidine | 205999-75-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-tert-butoxycarbonyl-(3R,4R)-dimethyl-4-(3-benzyloxyphenyl)piperidine
• 英文别名: tert-butyl (3R,4R)-3,4-dimethyl-4-(3-phenylmethoxyphenyl)piperidine-1-carboxylate
• CAS: 205999-75-3
• 化学式: C₂₅H₃₃NO₃
• 分子量: 395.542
• InChiKey: RSKXCKVMSXVPEA-UQBPGWFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-tert-butoxycarbonyl-(3R,4R)-dimethyl-4-(3-benzyloxyphenyl)piperidine 在 盐酸 、 碳酸氢钠 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 反应 22.0h， 以96%的产率得到(+)-4(R)-(3-benzyloxyphenyl)-3(R),4-dimethylpiperidine
  参考文献：
  名称：

  NOVEL OPIOID ANTAGONISTS

  摘要：

  某些喹诺里西啶和八氢吡啶吡嗪化合物、药物组合物及其使用方法被披露，例如作为阿片受体拮抗剂。

  公开号：

  US20070105863A1
• 作为产物：
  描述：

  (3R,4R)-3,4-二甲基-4-(3-羟基苯基)哌啶 在 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 1-tert-butoxycarbonyl-(3R,4R)-dimethyl-4-(3-benzyloxyphenyl)piperidine
  参考文献：
  名称：

  Investigation of the N-Substituent Conformation Governing Potency and μ Receptor Subtype-Selectivity in (+)-(3R,4R)-Dimethyl-4-(3-hydroxyphenyl)- piperidine Opioid Antagonists

  摘要：

  A study of the binding site requirements associated with the N-substituent of (+)-(3R,4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (4) derivatives was undertaken using a set of rigid vs flexible N-substituents. The study showed that compounds 7-9 bearing the trans-cinnamyl N-substituent most closely reproduced the potency at the opioid receptor of the flexible N-propylphenyl or N-propylcyclohexyl analogues previously reported. Neither the N-substituted cis-cinnamyl nor the cis-phenylcyclopropylmethyl compounds 10 and 11, respectively, showed high affinity for the opioid receptor. However, the N-trans-phenylcyclopropylmethyl compound 12 closely approximated the affinity of compounds 7-9. Additionally, we found that free rotation of the phenyl ring is necessary for high affinity binding and mu receptor subtype selectivity as the planar N-substituted thianaphthylmethyl and benzofuranylmethyl compounds 13 and 14 had significantly lower binding affinities. Altogether, these findings suggest that the high binding affinity, selectivity, and antagonist potency of N-propylphenyl or N-propylcyclohexyl analogues of (+)-(3R,4R)-dimethyl-4-(3-hydroxyphenyl) (4) are achieved via a conformation wherein the connecting chain of the N-substituents is extended away from piperidine nitrogen with the appended ring system rotated out-of-plane relative to the connecting chain atoms. This conformation is quite similar to that observed in the solid state for 5, as determined by single crystal X-ray analysis. Additionally, it was found that, unlike naltrexone, N-substituents bearing secondary carbons attached directly to the piperidine nitrogen of 4 suffer dramatic losses of potency vs analogues not substituted in this manner. Using a functional assay which measured stimulation or inhibition of [S-35]GTP-gamma-S binding, we show that the trans-cinnamyl analogues of (+)-(3R,4R)-dimethyl-4-(3-hydroxyphenyl)piperidine (4) retain opioid pure antagonist activity and possess picomolar antagonist potency at the mu receptor.

  DOI：

  10.1021/jm980063g

文献信息

• NOVEL OPIOID ANTAGONISTS
  申请人：Dolle E. Roland

  公开号：US20070105863A1

  公开（公告）日：2007-05-10

  Certain quinolizidine and octahydropyridopyrazine compounds, pharmaceutical compositions, and methods of their use, inter alia, as opioid receptor antagonists are disclosed.

  某些喹诺里西啶和八氢吡啶吡嗪化合物、药物组合物及其使用方法被披露，例如作为阿片受体拮抗剂。
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  公开号：US7538110B2

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  公开（公告）日：2014-11-25