4-([1,3,4]thiadiazol-2-ylthio)-6,7-dimethoxyquinazoline | 1234579-13-5

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 4-([1,3,4]thiadiazol-2-ylthio)-6,7-dimethoxyquinazoline
• 英文别名: 2-(6,7-Dimethoxyquinazolin-4-yl)sulfanyl-1,3,4-thiadiazole
• CAS: 1234579-13-5
• 化学式: C₁₂H₁₀N₄O₂S₂
• 分子量: 306.369
• InChiKey: LSZSIKHVAVGOPE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  124
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-巯基-1,3,4-噻二唑 、 4-氯-6,7-二甲氧基喹唑啉 在 potassium carbonate 作用下， 以 丁酮 为溶剂， 反应 3.0h， 以86%的产率得到4-([1,3,4]thiadiazol-2-ylthio)-6,7-dimethoxyquinazoline
  参考文献：
  名称：

  Discovery of the Novel Potent and Selective FLT3 Inhibitor 1-{5-[7-(3- Morpholinopropoxy)quinazolin-4-ylthio]-[1,3,4]thiadiazol-2-yl}-3-p-tolylurea and Its Anti-Acute Myeloid Leukemia (AML) Activitiesin Vitroandin Vivo

  摘要：

  Structure-activity relationship (SAR) studies of 2-(quinazolin-4-ylthio)thiazole derivatives, which are for optimizing the in vitro and in vivo antiacute myeloid leukemia (AML) activity of a previously identified FLT3 inhibitor 2-(6,7-dimethoxyquinazolin-4-ylthio)thiazole (1), are described. SAR studies centering around the head (thiazole) and tails (6- and 7-positions) of the quinazoline moiety of 1 led to the discovery of a series of compounds that exhibited significantly dincreased potency against FLT3-driven AML MV4-11 cells. Preliminary in vivo assays were carried out on three highly active compounds, whose results showed that 1-{5-[7-(3-morpholinopropoxy)quinazolin-4-ylthio]-[1,3,4]thiadiazol-2-yl}-3-p-tolylurea (20c) had the highest in vivo activity. Further in vitro and in vivo anti-AML studies were then performed on 20c; in an MV4-11 xenograft mouse model, a once-daily dose of 20c at 100 mg/kg for 18 days led to complete tumor regression without obvious toxicity. Western blot and immunohistochemical analysis were carried out to illustrate the mechanism of action of 20c.

  DOI：

  10.1021/jm300042x

文献信息

• Discovery of the Novel Potent and Selective FLT3 Inhibitor 1-{5-[7-(3- Morpholinopropoxy)quinazolin-4-ylthio]-[1,3,4]thiadiazol-2-yl}-3-<i>p</i>-tolylurea and Its Anti-Acute Myeloid Leukemia (AML) Activities<i>in Vitro</i>and<i>in Vivo</i>
  作者：Wei-Wei Li、Xiao-Yan Wang、Ren-Lin Zheng、Heng-Xiu Yan、Zhi-Xing Cao、Lei Zhong、Ze-Rong Wang、Pan Ji、Ling-Ling Yang、Li-Jiao Wang、Yong Xu、Jing-Jing Liu、Jiao Yang、Chun-Hui Zhang、Shuang Ma、Shan Feng、Qi-Zheng Sun、Yu-Quan Wei、Sheng-Yong Yang

  DOI：10.1021/jm300042x

  日期：2012.4.26

  Structure-activity relationship (SAR) studies of 2-(quinazolin-4-ylthio)thiazole derivatives, which are for optimizing the in vitro and in vivo antiacute myeloid leukemia (AML) activity of a previously identified FLT3 inhibitor 2-(6,7-dimethoxyquinazolin-4-ylthio)thiazole (1), are described. SAR studies centering around the head (thiazole) and tails (6- and 7-positions) of the quinazoline moiety of 1 led to the discovery of a series of compounds that exhibited significantly dincreased potency against FLT3-driven AML MV4-11 cells. Preliminary in vivo assays were carried out on three highly active compounds, whose results showed that 1-5-[7-(3-morpholinopropoxy)quinazolin-4-ylthio]-[1,3,4]thiadiazol-2-yl}-3-p-tolylurea (20c) had the highest in vivo activity. Further in vitro and in vivo anti-AML studies were then performed on 20c; in an MV4-11 xenograft mouse model, a once-daily dose of 20c at 100 mg/kg for 18 days led to complete tumor regression without obvious toxicity. Western blot and immunohistochemical analysis were carried out to illustrate the mechanism of action of 20c.