2-amino-6-benzoyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide | 62821-67-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并吡啶类
• 英文名称: 2-amino-6-benzoyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide
• 英文别名: ZW-1072；2-amino-6-benzoyl-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid amide；2-amino-6-benzoyl-5,7-dihydro-4H-thieno[2,3-c]pyridine-3-carboxamide
• CAS: 62821-67-4
• 化学式: C₁₅H₁₅N₃O₂S
• 分子量: 301.369
• InChiKey: FILBDBALBCFWTA-UHFFFAOYSA-N

物化性质

• 熔点：
  239 °C
• 沸点：
  508.9±50.0 °C(Predicted)
• 密度：
  1.402±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  118
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-amino-6-benzoyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide 、 N,N-二甲基甲酰胺 在 盐酸 作用下， 以 乙醇 为溶剂， 生成 7-benzoyl-5,6,7,8-tetrahydro-3H-pyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4-one
  参考文献：
  名称：

  Manhas,M.S.; Amin,S.G., Journal of Heterocyclic Chemistry, 1977, vol. 14, p. 161 - 164

  摘要：

  DOI：
• 作为产物：
  描述：

  1-苯酰基-4-哌啶酮 、 氰乙酰胺 在 吗啉 、 1,2,3,4,5,6,7,8-八硫杂环辛烷 作用下， 以 乙醇 为溶剂， 反应 4.0h， 以77%的产率得到2-amino-6-benzoyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide
  参考文献：
  名称：

  5-Aminothiophene-2,4-dicarboxamide analogues as hepatitis B virus capsid assembly effectors

  摘要：

  Chronic hepatitis B virus (HBV) infection represents a major health threat. Current FDA-approved drugs do not cure HBV. Targeting HBV core protein (Cp) provides an attractive approach toward HBV inhibition and possibly infection cure. We have previously identified and characterized a 5-amino-3-methylthiophene-2,4-dicarboxamide (ATDC) compound as a structurally novel hit for capsid assembly effectors (CAEs). We report herein hit validation through studies on absorption, distribution, metabolism and excretion (ADME) properties and pharmacokinetics (PK), and hit optimization via analogue synthesis aiming to probe the structure-activity relationship (SAR) and structure-property relationship (SPR). In the end, these medicinal chemistry efforts led to the identification of multiple analogues strongly binding to Cp, potently inhibiting HBV replication in nanomolar range without cytotoxicity, and exhibiting good oral bioavailability (F). Two of our analogues, 19o (EC50 = 0.11 mu M, CC50 > 100 mu M = 25%) and 19k (EC50 = 0.31 mu M, CC50 > 100 mu M, F = 46%), displayed overall lead profiles superior to reported CAEs 7-10 used in our studies. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.12.047

文献信息

• INHIBITORS OF HEPATITIS B VIRUS TARGETING CAPSID ASSEMBLY
  申请人：Sarafianos Stefan G.

  公开号：US20190092742A1

  公开（公告）日：2019-03-28

  The present invention provides novel compounds and methods for treating, preventing or inhibiting hepatitis B virus (HBV).

  本发明提供了用于治疗、预防或抑制乙型肝炎病毒（HBV）的新型化合物和方法。
• Inhibitors of hepatitis B virus targeting capsid assembly
  申请人：THE CURATORS OF THE UNIVERSITY OF MISSOURI

  公开号：US10759774B2

  公开（公告）日：2020-09-01

  The present invention provides novel compounds and methods for treating, preventing or inhibiting hepatitis B virus (HBV).

  本发明提供了用于治疗、预防或抑制乙型肝炎病毒（HBV）的新型化合物和方法。
• MANHAS M. S.; AMIN S. G., J. HETEROCYCL. CHEM. <JHTC-AD>, 1977, 14, NO 1, 161-164
  作者：MANHAS M. S.、 AMIN S. G.

  DOI：——

  日期：——
• Manhas,M.S.; Amin,S.G., Journal of Heterocyclic Chemistry, 1977, vol. 14, p. 161 - 164
  作者：Manhas,M.S.、Amin,S.G.

  DOI：——

  日期：——
• 5-Aminothiophene-2,4-dicarboxamide analogues as hepatitis B virus capsid assembly effectors
  作者：Jing Tang、Andrew D. Huber、Dallas L. Pineda、Kelsey N. Boschert、Jennifer J. Wolf、Jayakanth Kankanala、Jiashu Xie、Stefan G. Sarafianos、Zhengqiang Wang

  DOI：10.1016/j.ejmech.2018.12.047

  日期：2019.2

  Chronic hepatitis B virus (HBV) infection represents a major health threat. Current FDA-approved drugs do not cure HBV. Targeting HBV core protein (Cp) provides an attractive approach toward HBV inhibition and possibly infection cure. We have previously identified and characterized a 5-amino-3-methylthiophene-2,4-dicarboxamide (ATDC) compound as a structurally novel hit for capsid assembly effectors (CAEs). We report herein hit validation through studies on absorption, distribution, metabolism and excretion (ADME) properties and pharmacokinetics (PK), and hit optimization via analogue synthesis aiming to probe the structure-activity relationship (SAR) and structure-property relationship (SPR). In the end, these medicinal chemistry efforts led to the identification of multiple analogues strongly binding to Cp, potently inhibiting HBV replication in nanomolar range without cytotoxicity, and exhibiting good oral bioavailability (F). Two of our analogues, 19o (EC50 = 0.11 mu M, CC50 > 100 mu M = 25%) and 19k (EC50 = 0.31 mu M, CC50 > 100 mu M, F = 46%), displayed overall lead profiles superior to reported CAEs 7-10 used in our studies. (C) 2018 Elsevier Masson SAS. All rights reserved.