7-(2-chloro-6-fluorophenyl)-5-(3,4-dichlorophenyl)-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidine | 1320361-46-3

• 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: 7-(2-chloro-6-fluorophenyl)-5-(3,4-dichlorophenyl)-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidine
• 英文别名: 7-(2-Chloro-6-fluoro-phenyl)-5-(3,4-dichlorophenyl)-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidine
• CAS: 1320361-46-3
• 化学式: C₁₇H₁₀Cl₃FN₄
• 分子量: 395.651
• InChiKey: FMCZWJJJBDRXAY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  25
• 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：
  4

反应信息

• 作为反应物：
  描述：

  7-(2-chloro-6-fluorophenyl)-5-(3,4-dichlorophenyl)-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77%的产率得到cis-7-(2-chloro-6-fluorophenyl)-5-(3,4-dichlorophenyl)-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-氯-6-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 7-(2-chloro-6-fluorophenyl)-5-(3,4-dichlorophenyl)-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。
• US8921381B2
  申请人：——

  公开号：US8921381B2

  公开（公告）日：2014-12-30
• US9533990B2
  申请人：——

  公开号：US9533990B2

  公开（公告）日：2017-01-03
• [EN] NOVEL INHIBITORS OF SECRETION OF HEPATITIS B VIRUS ANTIGENS<br/>[FR] NOUVEAUX INHIBITEURS DE LA SÉCRÉTION D'ANTIGÈNES DU VIRUS DE L'HÉPATITE B
  申请人：INST HEPATITIS & VIRUS RES

  公开号：WO2012047856A2

  公开（公告）日：2012-04-12

  Pharmaceutical compositions of the invention comprise triazolopyrimidines useful for the treatment of hepatitis virus in a patient.
• Design, Synthesis, and Biological Evaluation of Triazolo-pyrimidine Derivatives as Novel Inhibitors of Hepatitis B Virus Surface Antigen (HBsAg) Secretion
  作者：Wenquan Yu、Cally Goddard、Elizabeth Clearfield、Courtney Mills、Tong Xiao、Haitao Guo、John D. Morrey、Neil E. Motter、Kang Zhao、Timothy M. Block、Andrea Cuconati、Xiaodong Xu

  DOI：10.1021/jm200696v

  日期：2011.8.25

  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.