1-(4-(2,6-diaminopyrimidin-4-yl)piperazin-1-yl)ethanone | 850071-11-3

• 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-(2,6-diaminopyrimidin-4-yl)piperazin-1-yl)ethanone
• 英文别名: 1-[4-(2,6-Diaminopyrimidin-4-yl)piperazin-1-yl]ethanone
• CAS: 850071-11-3
• 化学式: C₁₀H₁₆N₆O
• mdl: MFCD22742481
• 分子量: 236.277
• InChiKey: VXWNDGGVTGJLDL-UHFFFAOYSA-N

物化性质

• 熔点：
  274 °C
• 沸点：
  613.7±65.0 °C(Predicted)
• 密度：
  1.349±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  1-乙酰哌嗪 、 2,4-二氨基-6-氯嘧啶 以 水 为溶剂， 反应 21.0h， 以67%的产率得到1-(4-(2,6-diaminopyrimidin-4-yl)piperazin-1-yl)ethanone
  参考文献：
  名称：

  新型5-氨基噻唑并[4,5- d ]嘧啶类的合成，作为大肠杆菌和金黄色葡萄球菌SecA抑制剂

  摘要：

  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。

  DOI：

  10.1016/j.bmc.2010.10.027

文献信息

• Pteridine derivatives useful for making pharmaceutical compositions
  申请人：Waer Jozef Albert Mark

  公开号：US20070032477A1

  公开（公告）日：2007-02-08

  This invention relates to a group of substituted pteridine derivatives, their pharmaceutically acceptable salts, N-oxides, solvates, dihydro- and tetrahydro-derivatives, and enantiomers, possessing unexpectedly desirable pharmaceutical properties, in particular which are highly active immunosuppressive agents, and as such are useful in the treatment in transplant rejection and/or in the treatment of certain inflammatory diseases. These derivatives are also useful in preventing or treating cardiovascular disorders, allergic conditions, disorders of the central nervous system, TNF-α related disorders, viral diseases, inflammatory bowel diseases and cell proliferative disorders.

  本发明涉及一类取代的喹噁啉衍生物，其药学上可接受的盐、N-氧化物、溶剂合物、二氢和四氢衍生物以及对映体，具有出乎意料的理想药理特性，尤其是高活性的免疫抑制剂，因此在移植排斥和/或某些炎症性疾病的治疗中非常有用。这些衍生物还可用于预防或治疗心血管疾病、过敏性疾病、中枢神经系统疾病、TNF-α相关疾病、病毒性疾病、炎症性肠病和细胞增殖性疾病。
• HETEROCYCLE-SUBSTITUTED PTERIDINE DERIVATIVES AND THEIR USE IN THERAPY
  申请人：4 AZA IP NV

  公开号：EP1673092B1

  公开（公告）日：2007-08-15
• Discovery of 7-<i>N</i>-Piperazinylthiazolo[5,4-<i>d</i>]pyrimidine Analogues as a Novel Class of Immunosuppressive Agents with in Vivo Biological Activity
  作者：Mi-Yeon Jang、Yuan Lin、Steven De Jonghe、Ling-Jie Gao、Bart Vanderhoydonck、Mathy Froeyen、Jef Rozenski、Jean Herman、Thierry Louat、Kristien Van Belle、Mark Waer、Piet Herdewijn

  DOI：10.1021/jm101254z

  日期：2011.1.27

  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.
• 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。