1-(4-(5-amino-2-(4-fluorophenyl)thiazolo[4,5-d]pyrimidin-7-yl)-piperazin-1-yl)-2-(4-chlorophenoxy)ethanone | 1262121-00-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1-(4-(5-amino-2-(4-fluorophenyl)thiazolo[4,5-d]pyrimidin-7-yl)-piperazin-1-yl)-2-(4-chlorophenoxy)ethanone
• 英文别名: 1-[4-[5-Amino-2-(4-fluorophenyl)-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]piperazin-1-yl]-2-(4-chlorophenoxy)ethanone
• CAS: 1262121-00-5
• 化学式: C₂₃H₂₀ClFN₆O₂S
• 分子量: 498.968
• InChiKey: YZBJNFUEGGXJFR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  126
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  1-(4-(2,6-diaminopyrimidin-4-yl)piperazin-1-yl)ethanone 在 吡啶 、 盐酸 、 四(三苯基膦)钯 、 硫酸 、 potassium carbonate 、 溶剂黄146 、 sodium nitrite 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 生成 1-(4-(5-amino-2-(4-fluorophenyl)thiazolo[4,5-d]pyrimidin-7-yl)-piperazin-1-yl)-2-(4-chlorophenoxy)ethanone
  参考文献：
  名称：

  Discovery of 7-N-Piperazinylthiazolo[5,4-d]pyrimidine Analogues as a Novel Class of Immunosuppressive Agents with in Vivo Biological Activity

  摘要：

  Herein we describe the synthesis and in vitro and in vivo activity of thiazolo[5,4-d]pyrimidines as a novel class of immunosuppressive agents, useful for preventing graft rejection after organ transplantation. This research resulted in the discovery of a series of compounds with potent activity in the mixed lymphocyte reaction (MLR) assay, which is well-known as the in vitro model for in vivo rejection after organ transplantation. The most potent congeners displayed IC50 values of less than 50 nM in this MLR assay and hence are equipotent to cyclosporin A, a clinically used immunosuppressive drug. One representative of this series was further evaluated in a preclinical animal model of organ transplantation and showed excellent in vivo efficacy. It validates these compounds as new promising immunosuppressive drugs.

  DOI：

  10.1021/jm101254z

文献信息

• Synthesis of novel 5-amino-thiazolo[4,5-d]pyrimidines as E. coli and S. aureus SecA inhibitors
  作者：Mi-Yeon Jang、Steven De Jonghe、Kenneth Segers、Jozef Anné、Piet Herdewijn

  DOI：10.1016/j.bmc.2010.10.027

  日期：2011.1

  An efficient synthesis of a library of 5-amino-thiazolo[4,5-d]pyrimidines is reported. Regioselective displacements of chlorines, as well as regioselective diazotation reactions are described, which allow the introduction of structural diversity on the scaffold by consecutive reactions. Screening of this focused library led to the discovery of SecA inhibitors from Escherichia coli and Staphylococcus

  报道了5-氨基噻唑并[4，5- d ]嘧啶的文库的有效合成。描述了氯的区域选择性置换以及区域选择性重氮化反应，其允许通过连续反应在支架上引入结构多样性。该聚焦文库的筛选导致发现了来自大肠杆菌和金黄色葡萄球菌的SecA抑制剂。