| 1257843-96-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• CAS: 1257843-96-1
• 化学式: C₂₄H₂₃NO₃
• 分子量: 373.452
• InChiKey: UOAYPHDWLJZGAM-QHCPKHFHSA-N

反应信息

• 作为反应物：
  描述：

  反-1-甲氧基-3-(三甲基硅氧基)-1,3-丁二烯 、 在 ytterbium(III) triflate 作用下， 以 四氢呋喃 为溶剂， 生成 (2S)-1-(4-methoxybenzyl)-2-[(4S)-2,2-diphenyl-1,3-dioxolan-4-yl]-2,3-dihydropyridin-4(1H)-one 、 (2R)-1-(4-methoxybenzyl)-2-[(4S)-2,2-diphenyl-1,3-dioxolan-4-yl]-2,3-dihydropyridin-4(1H)-one
  参考文献：
  名称：

  Synthesis and SAR studies of chiral non-racemic dexoxadrol analogues as uncompetitive NMDA receptor antagonists

  摘要：

  A series of chiral non-racemic dexoxadrol analogues with various substituents in position 4 of the piperidine ring was synthesized and pharmacologically evaluated. Only the enantiomers having (S)-configuration at the 2-position of the piperidine ring and 4-position of the dioxolane ring were considered. Key steps in the synthesis were an imino-Diels-Alder reaction of enantiomerically pure imine (S)-13, which had been obtained from D-mannitol, with Danishefsky's Diene 14 and the replacement of the p-methoxybenzyl protective group with a Cbz-group. It was shown that (S,S)-configuration of the ring junction (position 2 of the piperidine ring and position 4 of the dioxolane ring) and axial orientation of the C-4-substituent ((4S)-configuration) are crucial for high NMDA receptor affinity. 2-(2,2-Diphenyl-1,3-dioxolan-4-yl)piperidines with a hydroxy moiety ((S,S,S)-5, K-i = 28 nM), a fluorine atom ((S,S,S)-6, WMS-2539, K-i = 7 nM) and two fluorine atoms ((S,S)-7, K-i = 48 nM) in position 4 represent the most potent NMDA antagonists with high selectivity against sigma(1) and sigma(2) receptors and the polyamine binding site of the NMDA receptor. The NMDA receptor affinities of the new ligands were correlated with their electrostatic potentials, calculated gas phase proton affinities (negative enthalpies of deprotonation) and dipole moments. According to these calculations decreasing proton affinity and increasing dipole moment are correlated with decreasing NMDA receptor affinity. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.09.047
• 作为产物：
  描述：

  2,2-diphenyl-1,3-dioxolane-4-carbaldehyde 、 4-甲氧基苄胺 在 原甲酸三甲酯 作用下， 反应 14.0h， 生成
  参考文献：
  名称：

  Synthesis and SAR studies of chiral non-racemic dexoxadrol analogues as uncompetitive NMDA receptor antagonists

  摘要：

  A series of chiral non-racemic dexoxadrol analogues with various substituents in position 4 of the piperidine ring was synthesized and pharmacologically evaluated. Only the enantiomers having (S)-configuration at the 2-position of the piperidine ring and 4-position of the dioxolane ring were considered. Key steps in the synthesis were an imino-Diels-Alder reaction of enantiomerically pure imine (S)-13, which had been obtained from D-mannitol, with Danishefsky's Diene 14 and the replacement of the p-methoxybenzyl protective group with a Cbz-group. It was shown that (S,S)-configuration of the ring junction (position 2 of the piperidine ring and position 4 of the dioxolane ring) and axial orientation of the C-4-substituent ((4S)-configuration) are crucial for high NMDA receptor affinity. 2-(2,2-Diphenyl-1,3-dioxolan-4-yl)piperidines with a hydroxy moiety ((S,S,S)-5, K-i = 28 nM), a fluorine atom ((S,S,S)-6, WMS-2539, K-i = 7 nM) and two fluorine atoms ((S,S)-7, K-i = 48 nM) in position 4 represent the most potent NMDA antagonists with high selectivity against sigma(1) and sigma(2) receptors and the polyamine binding site of the NMDA receptor. The NMDA receptor affinities of the new ligands were correlated with their electrostatic potentials, calculated gas phase proton affinities (negative enthalpies of deprotonation) and dipole moments. According to these calculations decreasing proton affinity and increasing dipole moment are correlated with decreasing NMDA receptor affinity. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.09.047