spiro-<5-hydroxy-tetralin-1'-methyl-1,4'-piperidine> | 139157-95-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: spiro-<5-hydroxy-tetralin-1'-methyl-1,4'-piperidine>
• 英文别名: spiro-(5-hydroxy-tetralin-1'-methyl-1,4'-piperidine)；1'-methylspiro[7,8-dihydro-6H-naphthalene-5,4'-piperidine]-1-ol
• CAS: 139157-95-2
• 化学式: C₁₅H₂₁NO
• 分子量: 231.338
• InChiKey: XNGPBBXYIIXOQZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  聚合甲醛 、 spiro-<5-hydroxy-tetralin-1,4'-piperidine> 在 sodium cyanoborohydride 作用下， 以 水 为溶剂， 以84%的产率得到spiro-<5-hydroxy-tetralin-1'-methyl-1,4'-piperidine>
  参考文献：
  名称：

  Structure-activity studies of morphine fragments. III. Synthesis, opiate receptor binding, analgetic activity and conformational studies of spiro-[tetralin-1,4′-piperidines]

  摘要：

  A series of 5 spiro compounds, a new class of conformationally restricted analogs of 4-alkyl-4-(m-OH-phenyl) piperidines, have been synthesized and their affinities for mu, delta and kappa-opioid receptor sites and in vivo analgetic activities determined. All compounds show rather low affinities for the 3 receptors, with some modulation by the N-substituent and by the position of the phenolic group. To help understand the origin of this poor affinity compared to the unrestricted 4-alkyl-4-phenyl piperidines, energy conformation calculations were performed which indicated that all the analogs favor a phenyl equatorial over a phenyl axial conformer. Significant differences in the lowest energy conformation were found between these spiro analogs and both morphine and 4-n-propyl-4-(m-OH-phenyl) piperidines, 18 and 19 which are conformationally unrestricted, closely related analogs with high mu-affinity. These differences could account for their lower affinities. To continue the search for more active members of the family, structure variations which favor a phenyl-axial conformation have been identified and proposed for further study.

  DOI：

  10.1016/0223-5234(91)90003-6

文献信息

• Structure-activity studies of morphine fragments. III. Synthesis, opiate receptor binding, analgetic activity and conformational studies of spiro-[tetralin-1,4′-piperidines]
  作者：JA Lawson、L Toll、W Polgar、ET Uyeno、GH Loew

  DOI：10.1016/0223-5234(91)90003-6

  日期：1991.11

  A series of 5 spiro compounds, a new class of conformationally restricted analogs of 4-alkyl-4-(m-OH-phenyl) piperidines, have been synthesized and their affinities for mu, delta and kappa-opioid receptor sites and in vivo analgetic activities determined. All compounds show rather low affinities for the 3 receptors, with some modulation by the N-substituent and by the position of the phenolic group. To help understand the origin of this poor affinity compared to the unrestricted 4-alkyl-4-phenyl piperidines, energy conformation calculations were performed which indicated that all the analogs favor a phenyl equatorial over a phenyl axial conformer. Significant differences in the lowest energy conformation were found between these spiro analogs and both morphine and 4-n-propyl-4-(m-OH-phenyl) piperidines, 18 and 19 which are conformationally unrestricted, closely related analogs with high mu-affinity. These differences could account for their lower affinities. To continue the search for more active members of the family, structure variations which favor a phenyl-axial conformation have been identified and proposed for further study.