methyl 4,5-dihydro-2-(3-hydroxypyridin-2-yl)thiazole-4(R)-carboxylate | 133817-88-6

• 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: methyl 4,5-dihydro-2-(3-hydroxypyridin-2-yl)thiazole-4(R)-carboxylate
• 英文别名: methyl (4R)-2-(3-hydroxypyridin-2-yl)-4,5-dihydro-1,3-thiazole-4-carboxylate
• CAS: 133817-88-6
• 化学式: C₁₀H₁₀N₂O₃S
• 分子量: 238.267
• InChiKey: MXNMKXDOWGYTSV-LURJTMIESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  97.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 4,5-dihydro-2-(3-hydroxypyridin-2-yl)thiazole-4(R)-carboxylate 在 manganese(IV) oxide 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 29.0h， 生成 2-(3-hydroxypyridin-2-yl)thiazole-4-carboxylic acid
  参考文献：
  名称：

  Desazadesmethyldesferrithiocin Analogues as Orally Effective Iron Chelators

  摘要：

  Further structure-activity studies of desferrithiocin analogues are carried out. (S)-desazadesmethyldesferrithiocin, 2-(2-hydroxyphenyl)-Delta(2)-thiazoline-4(S)-carboxylic acid, serves as the principal framework in the current paper. Desazadesmethyldesferrithiocin can be structurally altered with facility, and data are already available on its iron-clearing properties and toxicity parameters. Four different kinds of structural modifications of this framework are undertaken: introduction of hydroxy, carboxy, or methoxy groups on the aromatic ring; alteration of the thiazoline ring; increasing the distance between the ligand donor atoms; and benz-fusion of the aromatic rings. The structural modifications described are shown to have a tremendous imp act on both the iron clearance and toxicity profiles of the desazadesmethyldesferrithiocin molecule. All of the compounds are assessed in a bile-duct-cannulated rodent model to determine iron clearance efficiency. Ligands which demonstrate an efficiency of greater than 2% are carried forward to the iron-overloaded primate for iron-clearing measurements. Ligands with efficiencies greater than 3% in the primate are then evaluated in a formal toxicity study in rodents. On the basis of the results of the present work, 2-(2,4-dihydroxyphenyl)-Delta(2)-thiazoline-4(S)-carboxylic acid is a promising candidate for clinical evaluation.

  DOI：

  10.1021/jm980340j
• 作为产物：
  描述：

  desmethyldesferrithiocin sodium salt 、 2,2-二甲氧基丙烷 在 对甲苯磺酸 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 以88%的产率得到methyl 4,5-dihydro-2-(3-hydroxypyridin-2-yl)thiazole-4(R)-carboxylate
  参考文献：
  名称：

  Evaluation of desferrithiocin and its synthetic analogs as orally effective iron chelators

  摘要：

  Desferrithiocin, a novel microbial siderophore isolated from cultures of Streptomyces antibioticus DSM 1865, and a number of its derivatives and analogues are evaluated for their ability to promote iron clearance. The compounds have been designed with the objective of identifying the structural features of desferrithiocin which render this ligand an orally effective iron chelator. The desferrithiocin aromatic hydroxyl and the thiazoline ring carboxyl group are shown to be central to desferrithiocin's activity. The ligand's methyl and the aromatic nitrogen play little role in the compound's efficacy. The animal model chosen for this study, the bile duct cannulated rat, provides information regarding both the chelator-induced total iron output and the kinetics of both biliary and urinary iron excretion.

  DOI：

  10.1021/jm00111a023

文献信息

• BERGERON, RAYMOND J.;WIEGAND, JAN;DIONIS, JOHN B.;EGLI-KARMAKKA, MAJIA;FR+, J. MED. CHEM., 34,(1991) N, C. 2072-2078
  作者：BERGERON, RAYMOND J.、WIEGAND, JAN、DIONIS, JOHN B.、EGLI-KARMAKKA, MAJIA、FR+

  DOI：——

  日期：——
• Desazadesmethyldesferrithiocin Analogues as Orally Effective Iron Chelators
  作者：Raymond J. Bergeron、Jan Wiegand、William R. Weimar、J. R. Timothy Vinson、Jörg Bussenius、Guo Wei Yao、James S. McManis

  DOI：10.1021/jm980340j

  日期：1999.1.1

  Further structure-activity studies of desferrithiocin analogues are carried out. (S)-desazadesmethyldesferrithiocin, 2-(2-hydroxyphenyl)-Delta(2)-thiazoline-4(S)-carboxylic acid, serves as the principal framework in the current paper. Desazadesmethyldesferrithiocin can be structurally altered with facility, and data are already available on its iron-clearing properties and toxicity parameters. Four different kinds of structural modifications of this framework are undertaken: introduction of hydroxy, carboxy, or methoxy groups on the aromatic ring; alteration of the thiazoline ring; increasing the distance between the ligand donor atoms; and benz-fusion of the aromatic rings. The structural modifications described are shown to have a tremendous imp act on both the iron clearance and toxicity profiles of the desazadesmethyldesferrithiocin molecule. All of the compounds are assessed in a bile-duct-cannulated rodent model to determine iron clearance efficiency. Ligands which demonstrate an efficiency of greater than 2% are carried forward to the iron-overloaded primate for iron-clearing measurements. Ligands with efficiencies greater than 3% in the primate are then evaluated in a formal toxicity study in rodents. On the basis of the results of the present work, 2-(2,4-dihydroxyphenyl)-Delta(2)-thiazoline-4(S)-carboxylic acid is a promising candidate for clinical evaluation.
• Evaluation of desferrithiocin and its synthetic analogs as orally effective iron chelators
  作者：Raymond J. Bergeron、Jan Wiegand、John B. Dionis、Majia Egli-Karmakka、Joerg Frei、Alica Huxley-Tencer、Heinrich H. Peter

  DOI：10.1021/jm00111a023

  日期：1991.7

  Desferrithiocin, a novel microbial siderophore isolated from cultures of Streptomyces antibioticus DSM 1865, and a number of its derivatives and analogues are evaluated for their ability to promote iron clearance. The compounds have been designed with the objective of identifying the structural features of desferrithiocin which render this ligand an orally effective iron chelator. The desferrithiocin aromatic hydroxyl and the thiazoline ring carboxyl group are shown to be central to desferrithiocin's activity. The ligand's methyl and the aromatic nitrogen play little role in the compound's efficacy. The animal model chosen for this study, the bile duct cannulated rat, provides information regarding both the chelator-induced total iron output and the kinetics of both biliary and urinary iron excretion.