2,4,6-trimethyl-N-[1-(2,4,6-trimethylphenyl)sulfonylpiperidin-4-yl]benzenesulfonamide | 185532-45-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2,4,6-trimethyl-N-[1-(2,4,6-trimethylphenyl)sulfonylpiperidin-4-yl]benzenesulfonamide
• CAS: 185532-45-0
• 化学式: C₂₃H₃₂N₂O₄S₂
• 分子量: 464.65
• InChiKey: JKQPLBVDUHUNGL-UHFFFAOYSA-N

物化性质

• 沸点：
  622.4±65.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,4,6-trimethyl-N-[1-(2,4,6-trimethylphenyl)sulfonylpiperidin-4-yl]benzenesulfonamide 在 氢溴酸 、 sodium hydride 、 苯酚 作用下， 以 二氯甲烷 为溶剂， 生成 N,N'-Bis(4-piperidinyl)-1,3-propanediamine
  参考文献：
  名称：

  Polyamine Analogue Regulation of NMDA MK-801 Binding:  A Structure−Activity Study

  摘要：

  A series of analogues and homologues of spermine were synthesized, and their impact on MK-801 binding to the N-methyl-D-aspartate (NMDA) receptor was evaluated. These tetraamines encompass both linear and cyclic compounds. The linear molecules include norspermine, N-1,N-11-diethylnorspermine, N-1,N-13-bis(2,2,2-trifluoroethyl)spermine, homospermine, and N-1,N-14-diethylhomospermine. The cyclic tetraamines consist of the piperidine analogues N-1-N-3-bis(4-piperidinyl)-1,3-diaminopropane, N-1,N-4-bis(4-piperidinyl)-1,4-diaminobutane, N-1,N-4-bis(4-piperidinylmethyl)-1,4-diaminobutane, and N-1,N-4-bis[2-(4-piperidinyl)ethyl]-1,4-diaminobutane and the pyridine analogues N-1-N-3-bis(4-pyridyl)-1,3-diaminopropane, N-1,N-4-bis(4-pyridyl)-1,4-diaminobutane, N-1,N-4-bis(4-pyridylmethyl)-1,4-diaminobutane, and N-1,N-4-bis[2-(4-pyridyl)-ethyl]-1,4-diaminobutane. This structure-activity set makes it possible to establish the importance of charge, intercharge distance, and terminal nitrogen substitution on polyamine-regulated MK-801 binding in the NMDA channel. Four families of tetraamines are included in this set: norspermines, spermines, homospermines, and tetraazaoctadecanes. Calculations employing a SYBYL modeling program revealed that the distance between terminal nitrogens ranges between 12.62 and 19.61 Angstrom. The tetraamines are constructed such that within families cyclics and acyclics have similar lengths but different nitrogen pK(a)'s and thus different protonation, or charge, states at physiological pH. The pK(a) values-for all nitrogens of each molecule and its protonation state at physiological pH are described. The modifications at the' terminal nitrogens include introduction of ethyl and beta,beta,beta-trifluoroethyl groups and incorporation into piperidinyl or pyridyl systems. The studies clearly indicate that polyamine length, charge, and terminal nitrogen substitution have a significant effect on how the tetraamine regulates MK-801 binding to the NMDA receptor. Thus a structure-activity basis set on which future design of MK-801 agonists and antagonists can be based is now available.

  DOI：

  10.1021/jm960545x
• 作为产物：
  描述：

  2,4,6-三甲基苯磺酰氯 、 4-aminopiperidine dihydrochloride 在 sodium hydroxide 作用下， 以 二氯甲烷 为溶剂， 以73%的产率得到2,4,6-trimethyl-N-[1-(2,4,6-trimethylphenyl)sulfonylpiperidin-4-yl]benzenesulfonamide
  参考文献：
  名称：

  Polyamine Analogue Regulation of NMDA MK-801 Binding:  A Structure−Activity Study

  摘要：

  A series of analogues and homologues of spermine were synthesized, and their impact on MK-801 binding to the N-methyl-D-aspartate (NMDA) receptor was evaluated. These tetraamines encompass both linear and cyclic compounds. The linear molecules include norspermine, N-1,N-11-diethylnorspermine, N-1,N-13-bis(2,2,2-trifluoroethyl)spermine, homospermine, and N-1,N-14-diethylhomospermine. The cyclic tetraamines consist of the piperidine analogues N-1-N-3-bis(4-piperidinyl)-1,3-diaminopropane, N-1,N-4-bis(4-piperidinyl)-1,4-diaminobutane, N-1,N-4-bis(4-piperidinylmethyl)-1,4-diaminobutane, and N-1,N-4-bis[2-(4-piperidinyl)ethyl]-1,4-diaminobutane and the pyridine analogues N-1-N-3-bis(4-pyridyl)-1,3-diaminopropane, N-1,N-4-bis(4-pyridyl)-1,4-diaminobutane, N-1,N-4-bis(4-pyridylmethyl)-1,4-diaminobutane, and N-1,N-4-bis[2-(4-pyridyl)-ethyl]-1,4-diaminobutane. This structure-activity set makes it possible to establish the importance of charge, intercharge distance, and terminal nitrogen substitution on polyamine-regulated MK-801 binding in the NMDA channel. Four families of tetraamines are included in this set: norspermines, spermines, homospermines, and tetraazaoctadecanes. Calculations employing a SYBYL modeling program revealed that the distance between terminal nitrogens ranges between 12.62 and 19.61 Angstrom. The tetraamines are constructed such that within families cyclics and acyclics have similar lengths but different nitrogen pK(a)'s and thus different protonation, or charge, states at physiological pH. The pK(a) values-for all nitrogens of each molecule and its protonation state at physiological pH are described. The modifications at the' terminal nitrogens include introduction of ethyl and beta,beta,beta-trifluoroethyl groups and incorporation into piperidinyl or pyridyl systems. The studies clearly indicate that polyamine length, charge, and terminal nitrogen substitution have a significant effect on how the tetraamine regulates MK-801 binding to the NMDA receptor. Thus a structure-activity basis set on which future design of MK-801 agonists and antagonists can be based is now available.

  DOI：

  10.1021/jm960545x

文献信息

• Polyamine Analogue Regulation of NMDA MK-801 Binding:  A Structure−Activity Study
  作者：Raymond J. Bergeron、William R. Weimar、Qianhong Wu、Yang Feng、James S. McManis

  DOI：10.1021/jm960545x

  日期：1996.1.1

  A series of analogues and homologues of spermine were synthesized, and their impact on MK-801 binding to the N-methyl-D-aspartate (NMDA) receptor was evaluated. These tetraamines encompass both linear and cyclic compounds. The linear molecules include norspermine, N-1,N-11-diethylnorspermine, N-1,N-13-bis(2,2,2-trifluoroethyl)spermine, homospermine, and N-1,N-14-diethylhomospermine. The cyclic tetraamines consist of the piperidine analogues N-1-N-3-bis(4-piperidinyl)-1,3-diaminopropane, N-1,N-4-bis(4-piperidinyl)-1,4-diaminobutane, N-1,N-4-bis(4-piperidinylmethyl)-1,4-diaminobutane, and N-1,N-4-bis[2-(4-piperidinyl)ethyl]-1,4-diaminobutane and the pyridine analogues N-1-N-3-bis(4-pyridyl)-1,3-diaminopropane, N-1,N-4-bis(4-pyridyl)-1,4-diaminobutane, N-1,N-4-bis(4-pyridylmethyl)-1,4-diaminobutane, and N-1,N-4-bis[2-(4-pyridyl)-ethyl]-1,4-diaminobutane. This structure-activity set makes it possible to establish the importance of charge, intercharge distance, and terminal nitrogen substitution on polyamine-regulated MK-801 binding in the NMDA channel. Four families of tetraamines are included in this set: norspermines, spermines, homospermines, and tetraazaoctadecanes. Calculations employing a SYBYL modeling program revealed that the distance between terminal nitrogens ranges between 12.62 and 19.61 Angstrom. The tetraamines are constructed such that within families cyclics and acyclics have similar lengths but different nitrogen pK(a)'s and thus different protonation, or charge, states at physiological pH. The pK(a) values-for all nitrogens of each molecule and its protonation state at physiological pH are described. The modifications at the' terminal nitrogens include introduction of ethyl and beta,beta,beta-trifluoroethyl groups and incorporation into piperidinyl or pyridyl systems. The studies clearly indicate that polyamine length, charge, and terminal nitrogen substitution have a significant effect on how the tetraamine regulates MK-801 binding to the NMDA receptor. Thus a structure-activity basis set on which future design of MK-801 agonists and antagonists can be based is now available.