3-(2-amino-6-methyl-pyridin-3-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-2-(benzo[d][1,3]dioxol-5-yl)-thiazol-3-ium chloride hydrochloride | 1026039-09-7

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 3-(2-amino-6-methyl-pyridin-3-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-2-(benzo[d][1,3]dioxol-5-yl)-thiazol-3-ium chloride hydrochloride
• CAS: 1026039-09-7
• 化学式: C₂₀H₂₂N₃O₃S*ClH*Cl
• 分子量: 456.393
• InChiKey: NOENEDWVJWHFAS-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  0.03
• 重原子数：
  29.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  81.48
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  2-(2-(benzo[d][1,3]dioxol-5-yl)-4-methylthiazol-5-yl)ethanol 、 3-(chloromethyl)-6-methylpyridin-2-ylamine hydrochloride 以 正丁醇 为溶剂， 反应 1.0h， 以15%的产率得到3-(2-amino-6-methyl-pyridin-3-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-2-(benzo[d][1,3]dioxol-5-yl)-thiazol-3-ium 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