(S)-desmethyldesferrithiocin, N-methylhydroxamate | 155879-99-5

• 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: (S)-desmethyldesferrithiocin, N-methylhydroxamate
• 英文别名: (4S)-4,5-Dihydro-N-hydroxy-2-(3-hydroxy-2-pyridinyl)-N-methyl-4-thiazolecarboxamide；(4S)-N-hydroxy-2-(3-hydroxypyridin-2-yl)-N-methyl-4,5-dihydro-1,3-thiazole-4-carboxamide
• CAS: 155879-99-5
• 化学式: C₁₀H₁₁N₃O₃S
• 分子量: 253.282
• InChiKey: PSNFTAXBPPSFKP-ZCFIWIBFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  111
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-甲基羟胺盐酸盐 、 (S)-desmethyldesferrithiocin 在 (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， 以47%的产率得到(S)-desmethyldesferrithiocin, N-methylhydroxamate
  参考文献：
  名称：

  The Desferrithiocin Pharmacophore

  摘要：

  The (S)-desferrithiocin (DFT) skeleton is shown to be a useful pharmacophore on which to design orally effective iron chelators. While the study clearly indicates that formal reduction of the desazadesmethyldesferrithiocin thiazoline to a thiazolidine (6), expansion of the desmethyldesferrithiocin thiazoline to a thiazine (7), or substitution of the thiazoline sulfur of desazadesmethyldesferrithiocin by an oxygen (8 and 9) lead to a substantial loss of activity, conversion of (S)-desmethyldesferrithiocin (1) to an N-methylhydroxamate (4) or to the hexacoordinate dihydroxamate ligand (5) results in active compounds. This investigation thus demonstrates which structural components of the siderophore are required for iron clearance after oral administration and suggests the use of the desferrithiocin platform as a vector for other chelators.

  DOI：

  10.1021/jm00036a005

文献信息

• [EN] USE OF METAL CHELATORS IN MANAGING INFECTIOUS DISEASES<br/>[FR] UTILISATION DE CHÉLATEURS DE MÉTAUX DANS LA GESTION DE MALADIES INFECTIEUSES
  申请人：UNIV FLORIDA

  公开号：WO2016154547A1

  公开（公告）日：2016-09-29

  The present invention provides methods using a compound capable of chelating a metal (e.g., iron) for treating and/or preventing infectious diseases. In particular, the metal chelators are desferrithiocin analogs, desazadesfemthiocin analogs, and HBED analogs of Formula (I-A)-(III-A). The invention further provides methods useful in inhibiting biofilm formation. The provided methods also include combination therapies comprising a metal chelator with another therapeutic agent (e.g., antibiotic). The infectious diseases and/or biofilm formation may occur in a subject diagnosed with cystic fibrosis.
• The Desferrithiocin Pharmacophore
  作者：Raymond J. Bergeron、Charles Z. Liu、James S. McManis、Michael X. B. Xia、Samuel E. Algee、Jan Wiegand

  DOI：10.1021/jm00036a005

  日期：1994.5

  The (S)-desferrithiocin (DFT) skeleton is shown to be a useful pharmacophore on which to design orally effective iron chelators. While the study clearly indicates that formal reduction of the desazadesmethyldesferrithiocin thiazoline to a thiazolidine (6), expansion of the desmethyldesferrithiocin thiazoline to a thiazine (7), or substitution of the thiazoline sulfur of desazadesmethyldesferrithiocin by an oxygen (8 and 9) lead to a substantial loss of activity, conversion of (S)-desmethyldesferrithiocin (1) to an N-methylhydroxamate (4) or to the hexacoordinate dihydroxamate ligand (5) results in active compounds. This investigation thus demonstrates which structural components of the siderophore are required for iron clearance after oral administration and suggests the use of the desferrithiocin platform as a vector for other chelators.