2-[3-(2-amino-6-chloro-pyridin-3-ylmethyl)-4-methyl-thiazol-5-yl]-ethanol chloride hydrochloride | 1026038-80-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-[3-(2-amino-6-chloro-pyridin-3-ylmethyl)-4-methyl-thiazol-5-yl]-ethanol chloride hydrochloride
• CAS: 1026038-80-1
• 化学式: C₁₂H₁₅ClN₃OS*ClH*Cl
• 分子量: 356.704
• InChiKey: SOEPUBZRSGUAAI-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -1.02
• 重原子数：
  20.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  63.02
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2-[3-(2-amino-6-chloro-pyridin-3-ylmethyl)-4-methyl-thiazol-5-yl]-ethanol chloride hydrochloride 在 sodium hydroxide 、 potassium hexacyanoferrate(III) 作用下， 反应 0.17h， 生成 N-(2-amino-6-chloro-pyridin-3-ylmethyl)-N-{2-[2-[(2-amino-6-chloro-pyridin-3-ylmethyl)-formyl-amino]-1-(2-hydroxy-ethyl)-propenyldisulfanyl]-4-hydroxy-1-methyl-but-1-enyl}-formamide
  参考文献：
  名称：

  Prodrug thiamine analogs as inhibitors of the enzyme transketolase

  摘要：

  Transketolase, a key enzyme in the pentose phosphate pathway, has been suggested as a target for inhibition in the treatment of cancer. Compound 5a ('N3'-pyridyl thiamine'; 3-(6-methyl-2-amino-pyridin-3-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-thiazol-3-ium chloride hydrochloride), an analog of the transketolase cofactor thiamine, is a potent transketolase inhibitor but suffers from poor pharmacokinetics due to high clearance and C-max linked toxicity. An efficient way of improving the pharmacokinetic profile of 5a is to prepare oxidized prodrugs which are slowly reduced in vivo yielding longer, sustained blood levels of the drug. The synthesis of such prodrugs and their evaluation in rodent models is reported. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.11.100
• 作为产物：
  描述：

  4-甲基-5-(beta-羟乙基)噻唑 、 6-chloro-3-chloromethyl-pyridin-2-ylamine hydrochloride 反应 0.5h， 以40%的产率得到2-[3-(2-amino-6-chloro-pyridin-3-ylmethyl)-4-methyl-thiazol-5-yl]-ethanol chloride hydrochloride
  参考文献：
  名称：

  Synthesis, in vitro and in vivo activity of thiamine antagonist transketolase inhibitors

  摘要：

  Tumor cells extensively utilize the pentose phosphate pathway for the synthesis of ribose. Transketolase is a key enzyme in this pathway and has been suggested as a target for inhibition in the treatment of cancer. In a pharmacodynamic study, nude mice with xenografted HCT-116 tumors were dosed with 1 ('N3'-pyridyl thiamine'; 3-(6-methyl-2-amino-pyridin-3-ylmethyl)-5-(2-hydroxyethyl)-4-methyl-thiazol-3-ium chloride hydrochloride), an analog of thiamine, the co-factor of transketolase. Transketolase activity was almost completely suppressed in blood, spleen, and tumor cells, but there was little effect on the activity of the other thiamine-utilizing enzymes alpha-ketoglutarate dehydrogenase or glucose-6-phosphate dehydrogenase. Synthesis and SAR of transketolase inhibitors is described. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.11.101