4,6-dichloro-2-(benzylthio)-5-pyrimidinamine | 1440512-67-3

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 4,6-dichloro-2-(benzylthio)-5-pyrimidinamine
• 英文别名: 4,6-Dichloro-2-(benzylthio)-5-pyrimidineamine；2-benzylsulfanyl-4,6-dichloropyrimidin-5-amine
• CAS: 1440512-67-3
• 化学式: C₁₁H₉Cl₂N₃S
• 分子量: 286.185
• InChiKey: SVNIYLGANBOUOG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  77.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4,6-dichloro-2-(benzylthio)-5-pyrimidinamine 在 hydrazine hydrate 、 溶剂黄146 、 N,N-二异丙基乙胺 、 sodium nitrite 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成
  参考文献：
  名称：

  Design, synthesis and in vitro biological evaluation of novel [1,2,3]triazolo[4,5-d]pyrimidine derivatives containing a thiosemicarbazide moiety

  摘要：

  A series of hybrid molecules containing [1,2,3]triazolo[4,5-d]pyrimidine and thiosemicarbazide moieties were designed, synthesized and evaluated for their antiproliferative activities against MGC-803, NCI-H1650 and PC-3 human cancer cells. Some of the synthesized compounds showed moderate to good activity against three selected cancer cell lines. Among these compounds, compound 29 displayed the most potent antiproliferative activity as well as good selectivity between cancer cells and normal cells. Further mechanism studies revealed that compound 29 could obviously inhibit the colony formation and migration of MGC-803 as well as induced apoptosis. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.01.031
• 作为产物：
  描述：

  4,6-Dichloro-5-nitro-2-[(phenylmethyl)thio]-pyrimidine 在 铁粉 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 生成 4,6-dichloro-2-(benzylthio)-5-pyrimidinamine
  参考文献：
  名称：

  噻唑并[5,4- d ]嘧啶衍生物的设计，合成及抗增殖活性

  摘要：

  通过基于生物学验证的支架的原子替换策略，设计了一系列噻唑并[5,4- d ]嘧啶衍生物，然后评估其在癌细胞系中的抗增殖活性。进行了结构活性关系研究，从而鉴定出了化合物22，该化合物对HGC-27表现出良好的抗增殖活性，IC 50值为1.22μM，对GES-1细胞的毒性低。机理研究表明，化合物22抑制HGC-27的菌落形成和迁移以及诱导细胞凋亡。免疫印迹实验证明化合物22上调Bax的表达，下调Bcl-2的表达水平并切割caspased-3 / 9。这些发现表明，化合物22可以用作设计用于治疗人胃癌的新药物的模板。原子替代策略可能是设计新的抗癌药物的可行策略，并且可能会在药物设计中找到其应用。

  DOI：

  10.1016/j.ejmech.2017.07.039

文献信息

• Design, synthesis and antiproliferative activity of thiazolo[5,4-d]pyrimidine derivatives through the atom replacement strategy
  作者：Zhong-Hua Li、Xue-Qi Liu、Peng-Fei Geng、Ji Zhang、Jin-Lian Ma、Bo Wang、Tao-Qian Zhao、Bing Zhao、Xin-Hui Zhang、Bin Yu、Hong-Min Liu

  DOI：10.1016/j.ejmech.2017.07.039

  日期：2017.9

  A series of thiazolo[5,4-d]pyrimidine derivatives were designed through the atom replacement strategy based on biologically validated scaffolds and then evaluated for their antiproliferative activities on cancer cell lines. The structure-activity relationship studies were conducted, leading to the identification of compound 22, which exhibited good antiproliferative activity against HGC-27 with an

  通过基于生物学验证的支架的原子替换策略，设计了一系列噻唑并[5,4- d ]嘧啶衍生物，然后评估其在癌细胞系中的抗增殖活性。进行了结构活性关系研究，从而鉴定出了化合物22，该化合物对HGC-27表现出良好的抗增殖活性，IC 50值为1.22μM，对GES-1细胞的毒性低。机理研究表明，化合物22抑制HGC-27的菌落形成和迁移以及诱导细胞凋亡。免疫印迹实验证明化合物22上调Bax的表达，下调Bcl-2的表达水平并切割caspased-3 / 9。这些发现表明，化合物22可以用作设计用于治疗人胃癌的新药物的模板。原子替代策略可能是设计新的抗癌药物的可行策略，并且可能会在药物设计中找到其应用。
• Design, synthesis, and biological evaluation of new thiazolo[5,4-d]pyrimidine derivatives as potent antiproliferative agents
  作者：Zhong-Hua Li、Xue-Qi Liu、Peng-Fei Geng、Jin-Lian Ma、Tao-Qian Zhao、Hao-Ming Wei、Bin Yu、Hong-Min Liu

  DOI：10.1039/c7md00165g

  日期：——

  A series of thiazolo[5,4-d]pyrimidine derivatives were synthesized and evaluated for their antiproliferative activities against several human cancer cell lines. Structure–activity relationship studies were carried out, showing that most of the target compounds had good inhibition against the tested cell lines. Among them, compound 7i exhibited potent inhibition against human gastric cancer cells MGC-803

  合成了一系列噻唑并[5,4- d ]嘧啶衍生物，并评估了其对几种人类癌细胞系的抗增殖活性。进行了结构-活性关系研究，结果表明大多数目标化合物对受试细胞系均具有良好的抑制作用。其中，化合物7i对人胃癌细胞MGC-803和HGC-27表现出强抑制作用，IC 50值分别为4.64和5.07μM，在MGC-803和GES-1之间的选择性约为12倍，表明相对较低对正常细胞有毒性。化合物7i的效力和低毒性使噻唑洛[5,4- d]嘧啶是一种有吸引力的支架，用于设计选择性靶向MGC-803细胞的新衍生物。
• 一种手性嘧啶并三唑类替格瑞洛的制备方法
  申请人：南通常佑药业科技有限公司

  公开号：CN115160320A

  公开（公告）日：2022-10-11

  本发明公开了一种手性嘧啶并三唑类替格瑞洛的制备方法，包括六个步骤：1）中间体Ⅰ和中间体Ⅱ缩合反应后完成中间体Ⅲ的制备；2）中间体Ⅲ经过环合反应实现中间体Ⅳ的制备；3）中间体Ⅳ和中间体Ⅴ亲核取代增长碳链得到中间体Ⅵ；4）中间体Ⅵ在酸作用下脱去保护得到中间体Ⅶ；5）中间体Ⅶ经过丙烷基化反应实现中间体Ⅷ的制备；6）中间体Ⅷ经过胺化反应实现替格瑞洛的制备。本发明采用上述六步合成工艺，大大缩短了合成替格瑞洛的线路，简化了替格瑞洛的合成工序，采用价格低廉且易获得的起始原料，降低了制备替格瑞洛的成本，利用低温合成反应，使反应条件更加温和，减少了反应副产物的产生，避免了能源的损耗，从而保证了替格瑞洛的纯化。
• Design, synthesis and in vitro biological evaluation of novel [1,2,3]triazolo[4,5-d]pyrimidine derivatives containing a thiosemicarbazide moiety
  作者：Peng-Fei Geng、Xue-Qi Liu、Tao-Qian Zhao、Cong-Cong Wang、Zhong-Hua Li、Ji Zhang、Hao-Ming Wei、Biao Hu、Li-Ying Ma、Hong-Min Liu

  DOI：10.1016/j.ejmech.2018.01.031

  日期：2018.2

  A series of hybrid molecules containing [1,2,3]triazolo[4,5-d]pyrimidine and thiosemicarbazide moieties were designed, synthesized and evaluated for their antiproliferative activities against MGC-803, NCI-H1650 and PC-3 human cancer cells. Some of the synthesized compounds showed moderate to good activity against three selected cancer cell lines. Among these compounds, compound 29 displayed the most potent antiproliferative activity as well as good selectivity between cancer cells and normal cells. Further mechanism studies revealed that compound 29 could obviously inhibit the colony formation and migration of MGC-803 as well as induced apoptosis. (C) 2018 Elsevier Masson SAS. All rights reserved.