5-(4-chlorophenyl)-7-(2,6-difluorophenyl)-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidine | 1320361-30-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并嘧啶类
• 英文名称: 5-(4-chlorophenyl)-7-(2,6-difluorophenyl)-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidine
• 英文别名: 5-(4-Chlorophenyl)-7-(2,6-difluorophenyl)-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidine
• CAS: 1320361-30-5
• 化学式: C₁₇H₁₁ClF₂N₄
• 分子量: 344.751
• InChiKey: VBMNVDDALBDOGF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  42.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(4-chlorophenyl)-7-(2,6-difluorophenyl)-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidine 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以84%的产率得到cis-5-(4-chlorophenyl)-7-(2,6-difluorophenyl)-4,5,6,7-tetrahydro[1,2,4]triazolo[1,5-a]pyrimidine
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Triazolo-pyrimidine Derivatives as Novel Inhibitors of Hepatitis B Virus Surface Antigen (HBsAg) Secretion

  摘要：

  The high levels of hepatitis B virus (HBV) surface antigen (HBsAg)-bearing subviral particles in the serum of chronically infected individuals play an important role in suppressing HBV-specific immune response and are only mildly affected by the current small molecule therapies. Thus, a therapy that specifically reduces HBsAg serum levels could be used in combination therapy with nucleos(t)ide drugs or permit therapeutic vaccination for the treatment of HBV infection. Herein, we report the design, synthesis, and evaluation of novel triazolo-pyrimidine inhibitors (1, 3, and 4) of HBsAg cellular secretion, with activity against drug-resistant HBV variants. Extensive SAR led to substantial improvements in the EC50 of the parent compound, 5 (HBF-0259), with the best being 3c, with EC50 = 1.4 +/- 0.4 mu M, SI >= 36. The lead candidates, both la (PBHBV-001) and 3c (PBHBV-2-15), were well-tolerated in both normal and HBV-transgenic mice and exhibited acceptable pharmacokinetics and bioavailability in Sprague-Dawley rats.

  DOI：

  10.1021/jm200696v
• 作为产物：
  描述：

  2,6-二氟苯甲醛 在 sodium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 5-(4-chlorophenyl)-7-(2,6-difluorophenyl)-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidine
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Triazolo-pyrimidine Derivatives as Novel Inhibitors of Hepatitis B Virus Surface Antigen (HBsAg) Secretion

  摘要：

  The high levels of hepatitis B virus (HBV) surface antigen (HBsAg)-bearing subviral particles in the serum of chronically infected individuals play an important role in suppressing HBV-specific immune response and are only mildly affected by the current small molecule therapies. Thus, a therapy that specifically reduces HBsAg serum levels could be used in combination therapy with nucleos(t)ide drugs or permit therapeutic vaccination for the treatment of HBV infection. Herein, we report the design, synthesis, and evaluation of novel triazolo-pyrimidine inhibitors (1, 3, and 4) of HBsAg cellular secretion, with activity against drug-resistant HBV variants. Extensive SAR led to substantial improvements in the EC50 of the parent compound, 5 (HBF-0259), with the best being 3c, with EC50 = 1.4 +/- 0.4 mu M, SI >= 36. The lead candidates, both la (PBHBV-001) and 3c (PBHBV-2-15), were well-tolerated in both normal and HBV-transgenic mice and exhibited acceptable pharmacokinetics and bioavailability in Sprague-Dawley rats.

  DOI：

  10.1021/jm200696v

文献信息

• NOVEL INHIBITORS OF SECRETION OF HEPATITIS B VIRUS ANTIGENS
  申请人：Xu Xiaodong

  公开号：US20130303552A1

  公开（公告）日：2013-11-14

  Pharmaceutical compositions of the invention comprise triazolopyrimidines useful for the treatment of hepatitis virus in a patient.

  本发明的制药组合物包括三唑嘧啶，可用于治疗患者的肝炎病毒。
• Hepatitis B core protein allosteric modulators
  申请人：Indiana University Research and Technology Corporation

  公开号：US10183936B2

  公开（公告）日：2019-01-22

  The present disclosure provides, in part, compounds having allosteric effector properties against Hepatitis B virus Cp. Also provided herein are methods of treating viral infections, such as hepatitis B, comprising administering to a patient in need thereof a disclosed compound.

  本公开内容部分提供了对乙型肝炎病毒 Cp 具有异生效应特性的化合物。本文还提供了治疗病毒感染（如乙型肝炎）的方法，包括向有需要的患者施用所公开的化合物。
• Hepatitis B core protein modulators
  申请人：Assembly Biosciences, Inc.

  公开号：US10377748B2

  公开（公告）日：2019-08-13

  The present disclosure provides, in part, compounds having allosteric effector properties against Hepatitis B virus Cp. Also provided herein are methods of treating viral infections, such as hepatitis B, comprising administering to a patient in need thereof a disclosed compound.

  本公开内容部分提供了对乙型肝炎病毒 Cp 具有异生效应特性的化合物。本文还提供了治疗病毒感染（如乙型肝炎）的方法，包括向有需要的患者施用所公开的化合物。
• Cyclic sulfamide compounds and methods of using same
  申请人：Assembly Biosciences, Inc.

  公开号：US11078170B2

  公开（公告）日：2021-08-03

  The present disclosure provides, in part, cyclic sulfamide compounds, and pharmaceutical compositions thereof, useful as modulators of Hepatitis B (HBV) core protein, and methods of treating Hepatitis B (HBV) infection.

  本公开部分提供了可用作乙型肝炎（HBV）核心蛋白调节剂的环状硫酰胺化合物及其药物组合物，以及治疗乙型肝炎（HBV）感染的方法。
• Methods for ameliorating infusion reactions
  申请人：ARBUTUS BIOPHARMA CORPORATION

  公开号：US11351118B2

  公开（公告）日：2022-06-07

  Certain embodiments of the invention provide methods of ameliorating an infusion reaction in a mammal in need thereof.

  本发明的某些实施方案提供了改善哺乳动物输液反应的方法。