N6,N10-dibenzyl-N16-benzyloxycarboyl-N1-(L-phenylalanine)-6,10-diaza-1,16-diaminohexadecane | 204689-76-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N6,N10-dibenzyl-N16-benzyloxycarboyl-N1-(L-phenylalanine)-6,10-diaza-1,16-diaminohexadecane
• 英文别名: N⁶,N¹⁰-dibenzyl-N¹⁶-benzyloxycarboyl-N¹-(L-phenylalanine)-6,10-diaza-1,16-diaminohexadecane
• CAS: 204689-76-9
• 化学式: C₄₅H₆₁N₅O₃
• 分子量: 720.011
• InChiKey: MGIOAXNAMBMVRK-QLKFWGTOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.72
• 重原子数：
  53.0
• 可旋转键数：
  26.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  99.93
• 氢给体数：
  3.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  N6,N10-dibenzyl-N16-benzyloxycarboyl-N1-(L-phenylalanine)-6,10-diaza-1,16-diaminohexadecane 在 palladium dihydroxide 氢气 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 25.0 ℃ 、413.68 kPa 条件下， 反应 20.0h， 生成 N¹-[N-(2-methoxyphenylacetamido)-L-phenylalanine]-6,10-diaza-1,16-diaminohexadecane
  参考文献：
  名称：

  摘要：

  Purpose. Twelve synthetic spider toxin analogs were prepared in an effort to better understand the structure-activity relationships of the polyamine portion of argiotoxin-636 (Arg-636), a noncompetitive NMDA receptor (NMDAR) antagonist.Methods. The 1,13-diamino-4,8-diazatridecane portion of the side chain of Arg-636 was systematically modified in an effort to further our knowledge of the structural requirements for the alkyl linker spacing between the amine nitrogens. Systematic isosteric replacement of each of the amine nitrogens in the polyamine moiety with either oxygen or carbon provided a series of compounds which were evaluated in vitro for NMDAR antagonist activity.Results. One-half of the heteroatoms found in Arg-636 were removed to provide analogs which maintained in vitro potency below 1 mu M. However, these simplified analogs produced similar or more pronounced effects on the cardiovascular system than Arg-636 in vivo.Conclusions. In this set of analogs, a minimum of three basic nitrogens in the side chain was required for maximum potency as NMDAR antagonists. Isosteric nitrogen substitutions in the polyamine chain reduced the in vitro potency of these analogs. An analog binding-conformation model was proposed to rationalize the inactivity of these isosterically substituted analogs.

  DOI：

  10.1023/a:1011988317683
• 作为产物：
  描述：

  N¹-benzyl-N⁵-(tert-butoxycarbonyl)-1,5-diaminopentane 在 potassium fluoride 、 sodium tetrahydroborate 、 Celite 、 magnesium sulfate 、 三乙胺 、 三氟乙酸 、 肼 作用下， 以 甲醇 、 二氯甲烷 、 氯仿 、 乙腈 为溶剂， 反应 123.0h， 生成 N6,N10-dibenzyl-N16-benzyloxycarboyl-N1-(L-phenylalanine)-6,10-diaza-1,16-diaminohexadecane
  参考文献：
  名称：

  摘要：

  Purpose. Twelve synthetic spider toxin analogs were prepared in an effort to better understand the structure-activity relationships of the polyamine portion of argiotoxin-636 (Arg-636), a noncompetitive NMDA receptor (NMDAR) antagonist.Methods. The 1,13-diamino-4,8-diazatridecane portion of the side chain of Arg-636 was systematically modified in an effort to further our knowledge of the structural requirements for the alkyl linker spacing between the amine nitrogens. Systematic isosteric replacement of each of the amine nitrogens in the polyamine moiety with either oxygen or carbon provided a series of compounds which were evaluated in vitro for NMDAR antagonist activity.Results. One-half of the heteroatoms found in Arg-636 were removed to provide analogs which maintained in vitro potency below 1 mu M. However, these simplified analogs produced similar or more pronounced effects on the cardiovascular system than Arg-636 in vivo.Conclusions. In this set of analogs, a minimum of three basic nitrogens in the side chain was required for maximum potency as NMDAR antagonists. Isosteric nitrogen substitutions in the polyamine chain reduced the in vitro potency of these analogs. An analog binding-conformation model was proposed to rationalize the inactivity of these isosterically substituted analogs.

  DOI：

  10.1023/a:1011988317683