(+/-)-trans-5-acetamido-2-hydroxy-3-(4-phenylpiperidino)tetralin | 120447-37-2

• 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: (+/-)-trans-5-acetamido-2-hydroxy-3-(4-phenylpiperidino)tetralin
• 英文别名: Acetamide, N-(5,6,7,8-tetrahydro-6-hydroxy-7-(4-phenyl-1-piperidinyl)-1-naphthalenyl)-trans-(+-)-；N-[(6S,7S)-6-hydroxy-7-(4-phenylpiperidin-1-yl)-5,6,7,8-tetrahydronaphthalen-1-yl]acetamide
• CAS: 120447-37-2
• 化学式: C₂₃H₂₈N₂O₂
• 分子量: 364.488
• InChiKey: RUVNANCEFYIYHW-GOTSBHOMSA-N

物化性质

• 熔点：
  201-205 °C(Solv: ethanol (64-17-5); water (7732-18-5))
• 沸点：
  588.3±50.0 °C(Predicted)
• 密度：
  1.208±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  52.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (+/-)-trans-5-acetamido-2-hydroxy-3-(4-phenylpiperidino)tetralin 在 palladium on activated charcoal 盐酸 、 氢气 、 硝酸 、 亚膦酸 、 对甲苯磺酸 、 溶剂黄146 、 sodium nitrite 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 5.0~25.0 ℃ 、275.79 kPa 条件下， 反应 6.5h， 生成 (2R,3R)-6-amino-3-(4-phenylpiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-ol
  参考文献：
  名称：

  脑胆碱能神经元的Vesamicol受体图与放射性碘标记的苯并呋喃唑位置异构体的关系图。

  摘要：

  阿尔茨海默氏病的特征在于进行性脑胆碱能神经元变性。与位于乙酰胆碱储存小泡的摄取转运蛋白上的维他命胺高亲和力结合的苯并维他命的放射性示踪剂类似物可提供胆碱能神经元完整性的体内标志物。合成了五个外消旋碘苯并呋喃唑醇的位置异构体（4'-，5-，6-，7-和8-IBVM），用碘125交换标记，并评估了中枢胆碱能神经元的体内标记物。只有两种异构体，即5-IBVM（5）和6-IBVM（10），在小鼠脑中的分布模式与胆碱能神经支配相一致：纹状体>>海马>或=皮质>下丘脑>>小脑。5-IBVM（5）的24小时组织与小脑浓度之比，纹状体高3至4倍，皮层和海马的比例要比6-IBVM高（10）。8-IBVM（16）和4'-IBVM（17）在所检查的任何大脑区域均未表现出选择性保留。在心脏中，只有5-IBVM（5）的心房/心室浓度比与高外周胆碱能神经元选择性一致。7-IBVM（14）异构体表现出异常的大脑分布模式

  DOI：

  10.1021/jm9507486
• 作为产物：
  描述：

  5,8-二氢-1-萘胺 在 间氯过氧苯甲酸 作用下， 以 乙醚 、 乙醇 、 苯 为溶剂， 反应 33.0h， 生成 (+/-)-trans-5-acetamido-2-hydroxy-3-(4-phenylpiperidino)tetralin
  参考文献：
  名称：

  Synthesis, in vitro acetylcholine-storage-blocking activities, and biological properties of derivatives and analogs of trans-2-(4-phenylpiperidino)cyclohexanol (vesamicol)

  摘要：

  Eighty-four analogues and derivatives of the acetylcholine-storage-blocking drug trans-2-(4-phenylpiperidino)-cyclohexanol (vesamicol) were synthesized, and their potencies were evaluated with the acetylcholine active-transport assay utilizing purified synaptic vesicles from Torpedo electric organ. The parent drug exhibits enantioselectivity, with (-)-vesamicol being 25-fold more potent than (+)-vesamicol. The atomic structure and absolute configuration of (+)-vesamicol were determined by X-ray crystallography. The absolute configuration of (-)-vesamicol is 1R,2R. Structure-activity evidence indicates that (-)-vesamicol does not act as an acetylcholine analogue. Alterations to all three rings can have large effects on potency. Unexpectedly, analogues locking the alcohol and ammonium groups trans-diequatorial or trans-diaxial both exhibit good potency. A potent benzovesamicol family has been discovered that is suitable for facile elaboration of the sort useful in affinity labeling and affinity chromatography applications. A good correlation was found between potencies as assessed by the acetylcholine transport assay and LD50 values in mouse.

  DOI：

  10.1021/jm00126a013

文献信息

• Synthesis, in vitro acetylcholine-storage-blocking activities, and biological properties of derivatives and analogs of trans-2-(4-phenylpiperidino)cyclohexanol (vesamicol)
  作者：Gary A. Rogers、Stanley M. Parsons、D. C. Anderson、Lena M. Nilsson、Ben A. Bahr、Wayne D. Kornreich、Rose Kaufman、Robert S. Jacobs、Bernard Kirtman

  DOI：10.1021/jm00126a013

  日期：1989.6

  Eighty-four analogues and derivatives of the acetylcholine-storage-blocking drug trans-2-(4-phenylpiperidino)-cyclohexanol (vesamicol) were synthesized, and their potencies were evaluated with the acetylcholine active-transport assay utilizing purified synaptic vesicles from Torpedo electric organ. The parent drug exhibits enantioselectivity, with (-)-vesamicol being 25-fold more potent than (+)-vesamicol. The atomic structure and absolute configuration of (+)-vesamicol were determined by X-ray crystallography. The absolute configuration of (-)-vesamicol is 1R,2R. Structure-activity evidence indicates that (-)-vesamicol does not act as an acetylcholine analogue. Alterations to all three rings can have large effects on potency. Unexpectedly, analogues locking the alcohol and ammonium groups trans-diequatorial or trans-diaxial both exhibit good potency. A potent benzovesamicol family has been discovered that is suitable for facile elaboration of the sort useful in affinity labeling and affinity chromatography applications. A good correlation was found between potencies as assessed by the acetylcholine transport assay and LD50 values in mouse.
• Vesamicol Receptor Mapping of Brain Cholinergic Neurons with Radioiodine- Labeled Positional Isomers of Benzovesamicol
  作者：Yong-Woon Jung、Kirk A. Frey、G. Keith Mulholland、Renato del Rosario、Phillip S. Sherman、David M. Raffel、Marcian E. Van Dort、David E. Kuhl、David L. Gildersleeve、Donald M. Wieland

  DOI：10.1021/jm9507486

  日期：1996.1.1

  facial nuclei. Except for cortex, regional brain levels of (-)-5-[123I]IBVM ((-)-[123I]5) at 4 h exhibited a linear correlation (r2 = 0.99) with endogenous levels of choline acetyltransferase. CONCLUSION: Vesamicol receptor mapping of cholinergic nerve terminals in murine brain can be achieved with 5-IBVM (5) and less robustly with 6-IBVM (10), whereas the brain localization of 7-IBVM (14) reflects high-affinity

  阿尔茨海默氏病的特征在于进行性脑胆碱能神经元变性。与位于乙酰胆碱储存小泡的摄取转运蛋白上的维他命胺高亲和力结合的苯并维他命的放射性示踪剂类似物可提供胆碱能神经元完整性的体内标志物。合成了五个外消旋碘苯并呋喃唑醇的位置异构体（4'-，5-，6-，7-和8-IBVM），用碘125交换标记，并评估了中枢胆碱能神经元的体内标记物。只有两种异构体，即5-IBVM（5）和6-IBVM（10），在小鼠脑中的分布模式与胆碱能神经支配相一致：纹状体>>海马>或=皮质>下丘脑>>小脑。5-IBVM（5）的24小时组织与小脑浓度之比，纹状体高3至4倍，皮层和海马的比例要比6-IBVM高（10）。8-IBVM（16）和4'-IBVM（17）在所检查的任何大脑区域均未表现出选择性保留。在心脏中，只有5-IBVM（5）的心房/心室浓度比与高外周胆碱能神经元选择性一致。7-IBVM（14）异构体表现出异常的大脑分布模式