(+/-)-trans,trans-N,N'-bis<4-oxo-4-<<5,6,7,8-tetrahydro-6-hydroxy-7-(4-phenylpiperidino)-1-naphthalenyl>amino>butanoyl>hydrazine

• 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,trans-N,N'-bis<4-oxo-4-<<5,6,7,8-tetrahydro-6-hydroxy-7-(4-phenylpiperidino)-1-naphthalenyl>amino>butanoyl>hydrazine
• 英文别名: N-[6-hydroxy-7-(4-phenylpiperidin-1-yl)-5,6,7,8-tetrahydronaphthalen-1-yl]-4-[2-[4-[[6-hydroxy-7-(4-phenylpiperidin-1-yl)-5,6,7,8-tetrahydronaphthalen-1-yl]amino]-4-oxobutanoyl]hydrazinyl]-4-oxobutanamide
• 化学式: C₅₀H₆₀N₆O₆
• 分子量: 841.063
• InChiKey: RPKDUSNTVQLLLU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  62
• 可旋转键数：
  12
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  163
• 氢给体数：
  6
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  5,8-二氢-1-萘胺 在 间氯过氧苯甲酸 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醚 、 乙醇 、 氯仿 、 苯 为溶剂， 反应 33.0h， 生成 (+/-)-trans,trans-N,N'-bis<4-oxo-4-<<5,6,7,8-tetrahydro-6-hydroxy-7-(4-phenylpiperidino)-1-naphthalenyl>amino>butanoyl>hydrazine
  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.