1-(3-氯苯基)-3-(5-巯基-[1,3,4]噻二唑-2-基)脲 | 294851-80-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 1-(3-氯苯基)-3-(5-巯基-[1,3,4]噻二唑-2-基)脲
• 英文名称: 1-(3-chlorophenyl)-3-(5-mercapto-[1,3,4]thiadiazol-2-yl)urea
• 英文别名: 1-(3-Chlorophenyl)-3-(5-mercapto-1,3,4-thiadiazol-2-yl)urea；1-(3-chlorophenyl)-3-(2-sulfanylidene-3H-1,3,4-thiadiazol-5-yl)urea
• CAS: 294851-80-2
• 化学式: C₉H₇ClN₄OS₂
• 分子量: 286.766
• InChiKey: ZLGQHKIKYOECDX-UHFFFAOYSA-N

物化性质

• 密度：
  1.69±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  123
• 氢给体数：
  3
• 氢受体数：
  4

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  1-(3-氯苯基)-3-(5-巯基-[1,3,4]噻二唑-2-基)脲 、 4-氯-6,7-二(2-甲氧基乙氧基)喹唑啉 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以60%的产率得到1-{5-[6,7-bis(2-methoxyethoxy)quinazolin-4-ylthio][1,3,4]thiadiazol-2-yl}-3-(3-chlorophenyl)urea
  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
• 作为产物：
  描述：

  2-氨基-5-巯基-1,3,4-噻二唑 、 间氯苯异氰酸酯 以 二氯甲烷 为溶剂， 生成 1-(3-氯苯基)-3-(5-巯基-[1,3,4]噻二唑-2-基)脲
  参考文献：
  名称：

  含有噻二唑脲的喹唑啉-4(3H)-1 类药物：抗增殖和抗血管生成活性的合成和评价

  摘要：

  设计、合成和生物学评估了一系列含有噻二唑脲的喹唑啉-4(3H)-one 试剂。化合物9f适度降低PC3细胞的增殖率（IC 50 = 17.7μ米)与索拉非尼相当（IC 50 = 17.3μ米）。当 HUVEC 细胞暴露于化合物9y (IC 50 = 6.1μ米). 为了测试化合物诱导细胞凋亡的潜力，使用膜联蛋白 V-FITC/碘化丙啶双染色测定。用9f处理 HUVEC 细胞后，它们经历了凋亡作用。大量的努力致力于收集跨 CAM 分析的综合数据。这些数据表明，9f适度抑制相应血管的生长。最后，蛋白质印迹的结果提出了一种作用机制，即化合物9f和9y抑制了 VEGFR-2 的磷酸化。

  DOI：

  10.1016/j.bioorg.2020.104553

文献信息

• Quinazolin-4(3H)-one based agents bearing thiadiazole-urea: Synthesis and evaluation of anti-proliferative and antiangiogenic activity
  作者：Aram Faraji、Rasoul Motahari、Zaman Hasanvand、Tayebeh Oghabi Bakhshaiesh、Mahsa Toolabi、Setareh Moghimi、Loghman Firoozpour、Mohammad Amin Boshagh、Roya Rahmani、Shima H.M.E. Ketabforoosh、Hamid Reza Bijanzadeh、Rezvan Esmaeili、Alireza Foroumadi

  DOI：10.1016/j.bioorg.2020.104553

  日期：2021.3

  A series of quinazolin-4(3H)-one based agents containing thiadiazole-urea were designed, synthesized, and biologically evaluated. The proliferation rate of PC3 cells was moderately reduced by compound 9f (IC50 = 17.7 μM)which was comparable with sorafenib (IC50 = 17.3 μM). There was also a significant reduction in the number of HUVEC cells, when they were exposed to compound 9y (IC50 = 6.1 μM). To

  设计、合成和生物学评估了一系列含有噻二唑脲的喹唑啉-4(3H)-one 试剂。化合物9f适度降低PC3细胞的增殖率（IC 50 = 17.7μ米)与索拉非尼相当（IC 50 = 17.3μ米）。当 HUVEC 细胞暴露于化合物9y (IC 50 = 6.1μ米). 为了测试化合物诱导细胞凋亡的潜力，使用膜联蛋白 V-FITC/碘化丙啶双染色测定。用9f处理 HUVEC 细胞后，它们经历了凋亡作用。大量的努力致力于收集跨 CAM 分析的综合数据。这些数据表明，9f适度抑制相应血管的生长。最后，蛋白质印迹的结果提出了一种作用机制，即化合物9f和9y抑制了 VEGFR-2 的磷酸化。
• Design, synthesis and evaluation of novel thienopyrimidine-based agents bearing diaryl urea functionality as potential inhibitors of angiogenesis
  作者：Aram Faraji、Tayebeh Oghabi Bakhshaiesh、Zaman Hasanvand、Rasoul Motahari、Elahe Nazeri、Mohammad Amin Boshagh、Loghman Firoozpour、Hossein Mehrabi、Ali Khalaj、Rezvan Esmaeili、Alireza Foroumadi

  DOI：10.1016/j.ejmech.2020.112942

  日期：2021.1
• 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.