4-amino-6-chloro-N-methyl-5-nitro-N-propylpyrimidine-2-carboxamide | 1228588-65-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 4-amino-6-chloro-N-methyl-5-nitro-N-propylpyrimidine-2-carboxamide
• CAS: 1228588-65-5
• 化学式: C₉H₁₂ClN₅O₃
• 分子量: 273.679
• InChiKey: UOXMUGDAIRIQEE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  118
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-amino-6-chloro-N-methyl-5-nitro-N-propylpyrimidine-2-carboxamide 在 manganese(IV) oxide 、 溶剂黄146 、 三乙胺 、 锌 作用下， 以 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.75h， 生成 4-amino-N-methyl-6,7-dioxo-N-propyl-8-[[4-(pyrrolidin-1-ylmethyl)phenyl]methyl]-5H-pteridine-2-carboxamide
  参考文献：
  名称：

  Identification and Optimization of Pteridinone Toll-like Receptor 7 (TLR7) Agonists for the Oral Treatment of Viral Hepatitis

  摘要：

  Pteridinone-based Toll-like receptor 7 (TLR7) agonists were identified as potent and selective alternatives to the previously reported adenine-based agonists, leading to the discovery of GS-9620. Analogues were optimized for the immunomodulatory activity and selectivity versus other TLRs, based on differential induction of key cytokines including interferon a (IFN-alpha) and tumor necrosis factor a (TNF-alpha). In addition, physicochemical properties were adjusted to achieve desirable in vivo pharmacokinetic and pharmacodynamic properties. GS-9620 is currently in clinical evaluation for the treatment of chronic hepatitis B (HBV) infection.

  DOI：

  10.1021/jm400815m
• 作为产物：
  描述：

  4,6-二氯-2-嘧啶羧酸 在 N-甲基吗啉 、 ammonium hydroxide 、 硫酸 、 硝酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N-甲基吡咯烷酮 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 49.0h， 生成 4-amino-6-chloro-N-methyl-5-nitro-N-propylpyrimidine-2-carboxamide
  参考文献：
  名称：

  Identification and Optimization of Pteridinone Toll-like Receptor 7 (TLR7) Agonists for the Oral Treatment of Viral Hepatitis

  摘要：

  Pteridinone-based Toll-like receptor 7 (TLR7) agonists were identified as potent and selective alternatives to the previously reported adenine-based agonists, leading to the discovery of GS-9620. Analogues were optimized for the immunomodulatory activity and selectivity versus other TLRs, based on differential induction of key cytokines including interferon a (IFN-alpha) and tumor necrosis factor a (TNF-alpha). In addition, physicochemical properties were adjusted to achieve desirable in vivo pharmacokinetic and pharmacodynamic properties. GS-9620 is currently in clinical evaluation for the treatment of chronic hepatitis B (HBV) infection.

  DOI：

  10.1021/jm400815m

文献信息

• MODULATORS OF TOLL-LIKE RECEPTORS
  申请人：Desai Manoj C.

  公开号：US20100143301A1

  公开（公告）日：2010-06-10

  Provided are modulators of TLRs of Formula II: pharmaceutically acceptable salts thereof, compositions containing such compounds, and therapeutic methods that include the administration of such compounds.

  提供了公式II的TLR调节剂：其药用盐，含有这类化合物的组合物，以及包括给予这类化合物的治疗方法。
• Modulators of toll-like receptors
  申请人：Gilead Sciences, Inc.

  公开号：US10172860B2

  公开（公告）日：2019-01-08

  Provided are modulators of TLRs of Formula II: pharmaceutically acceptable salts thereof, compositions containing such compounds, and therapeutic methods that include the administration of such compounds.

  所提供的是式 II 的 TLR 调节剂： 其药学上可接受的盐、含有此类化合物的组合物以及包括施用此类化合物的治疗方法。
• Intermediates for the preparation of modulators of toll-like receptors
  申请人：GILEAD SCIENCES, INC.

  公开号：EP2818469B1

  公开（公告）日：2017-02-15
• US8367670B2
  申请人：——

  公开号：US8367670B2

  公开（公告）日：2013-02-05
• US8629142B2
  申请人：——

  公开号：US8629142B2

  公开（公告）日：2014-01-14