N¹,N⁸-bis(tert-butoxycarbonyl)-N^!,N⁸-dihydroxy-3,6-dioxa-1,8-octanediamine | 241147-38-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N¹,N⁸-bis(tert-butoxycarbonyl)-N^!,N⁸-dihydroxy-3,6-dioxa-1,8-octanediamine
• 英文别名: tert-butyl N-hydroxy-N-[2-[2-[2-[hydroxy-[(2-methylpropan-2-yl)oxycarbonyl]amino]ethoxy]ethoxy]ethyl]carbamate
• CAS: 241147-38-6
• 化学式: C₁₆H₃₂N₂O₈
• 分子量: 380.439
• InChiKey: JZXNUMLGRVXJQV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  26
• 可旋转键数：
  13
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  118
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N¹,N⁸-bis(tert-butoxycarbonyl)-N^!,N⁸-dihydroxy-3,6-dioxa-1,8-octanediamine 在 盐酸 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 (4S)-N-hydroxy-N-[2-[2-[2-[hydroxy-[(4S)-2-(3-hydroxypyridin-2-yl)-4,5-dihydro-1,3-thiazole-4-carbonyl]amino]ethoxy]ethoxy]ethyl]-2-(3-hydroxypyridin-2-yl)-4,5-dihydro-1,3-thiazole-4-carboxamide
  参考文献：
  名称：

  Evaluation of the Desferrithiocin Pharmacophore as a Vector for Hydroxamates

  摘要：

  A series of (S)-desmethyldesferrithiocin (DMDFT, 1) hydroxamates and a bis-salicyl polyether hydroxamate are evaluated for their iron-clearing properties in rodents; some of these are further assessed in primates. These hydroxamates include (S)-desmethyldesferrithiocin, N-methylhydroxamate (2); (S)-desmethyldesferrithiocin, N-[5-(acetylhydroxyamino)pentyl]hydroxamate (3); desmethyldesferrithiocin, N-benzylhydroxamate (4); (S,S)-N-1, N-8-bis[4,5-dihydro-2-(3-hydroxy-2-pyridinyl)-4-thiazoyl]-N-1,N-8-dihydroxy-3,6-dioxa-1,8-octanediamine (5); and N-1,N-8-bis(2-hydroxybenzoyl)-N-1,N-8-dihydroxy-3,6-dioxa-1,8-octanediamine (6). The ligands are evaluated when given both orally (po) and subcutaneously (sc) in the bile-duct-cannulated rodent model. In iron-overloaded primates, ligands 1-4 are assessed when administered po and sc. The efficiencies of the hydroxamates are shown to vary considerably; giving the compounds sc consistently resulted in greater chelating efficiency in vivo. After oral administration in the primate, compound 3, a pentacoordinate unsymmetrical dihydroxamate, produces iron excretion sufficient to warrant further preclinical evaluation both as a potential orally active iron-chelating agent and as a parenteral iron chelator. The increased iron clearance of several of these ligands when administered sc versus po also underscores the idea that parenteral administration is a reasonable alternative to a less efficient, orally active device which would require large and frequent doses.

  DOI：

  10.1021/jm980611q
• 作为产物：
  描述：

  N-(苄氧基)氨基甲酸叔丁酯 在 palladium on activated charcoal 氢气 、 sodium hydride 作用下， 以 甲醇 为溶剂， 25.0~53.0 ℃ 、101.33 kPa 条件下， 反应 29.17h， 生成 N¹,N⁸-bis(tert-butoxycarbonyl)-N^!,N⁸-dihydroxy-3,6-dioxa-1,8-octanediamine
  参考文献：
  名称：

  Evaluation of the Desferrithiocin Pharmacophore as a Vector for Hydroxamates

  摘要：

  A series of (S)-desmethyldesferrithiocin (DMDFT, 1) hydroxamates and a bis-salicyl polyether hydroxamate are evaluated for their iron-clearing properties in rodents; some of these are further assessed in primates. These hydroxamates include (S)-desmethyldesferrithiocin, N-methylhydroxamate (2); (S)-desmethyldesferrithiocin, N-[5-(acetylhydroxyamino)pentyl]hydroxamate (3); desmethyldesferrithiocin, N-benzylhydroxamate (4); (S,S)-N-1, N-8-bis[4,5-dihydro-2-(3-hydroxy-2-pyridinyl)-4-thiazoyl]-N-1,N-8-dihydroxy-3,6-dioxa-1,8-octanediamine (5); and N-1,N-8-bis(2-hydroxybenzoyl)-N-1,N-8-dihydroxy-3,6-dioxa-1,8-octanediamine (6). The ligands are evaluated when given both orally (po) and subcutaneously (sc) in the bile-duct-cannulated rodent model. In iron-overloaded primates, ligands 1-4 are assessed when administered po and sc. The efficiencies of the hydroxamates are shown to vary considerably; giving the compounds sc consistently resulted in greater chelating efficiency in vivo. After oral administration in the primate, compound 3, a pentacoordinate unsymmetrical dihydroxamate, produces iron excretion sufficient to warrant further preclinical evaluation both as a potential orally active iron-chelating agent and as a parenteral iron chelator. The increased iron clearance of several of these ligands when administered sc versus po also underscores the idea that parenteral administration is a reasonable alternative to a less efficient, orally active device which would require large and frequent doses.

  DOI：

  10.1021/jm980611q