trifluoroethyl (R)-4-(2-chloro-4-fluorophenyl)-6-methyl-2-(2-thiazolyl)-1,4-dihydropyrimidin-5-carboxylate | 1005459-75-5

• 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: trifluoroethyl (R)-4-(2-chloro-4-fluorophenyl)-6-methyl-2-(2-thiazolyl)-1,4-dihydropyrimidin-5-carboxylate
• 英文别名: 2,2,2-trifluoroethyl (4R)-4-(2-chloro-4-fluorophenyl)-6-methyl-2-(1,3-thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate
• CAS: 1005459-75-5
• 化学式: C₁₇H₁₂ClF₄N₃O₂S
• 分子量: 433.814
• InChiKey: SQBWMXYRYPHMQB-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  91.8
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  trifluoroethyl (R)-4-(2-chloro-4-fluorophenyl)-6-methyl-2-(2-thiazolyl)-1,4-dihydropyrimidin-5-carboxylate 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 四氯化碳 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  Discovery and Pre-Clinical Characterization of Third-Generation 4-H Heteroaryldihydropyrimidine (HAP) Analogues as Hepatitis B Virus (HBV) Capsid Inhibitors

  摘要：

  Described herein are the discovery and structure activity relationship (SAR) studies of the third-generation 4-H heteroaryldihydropyrimidines (4-H HAPs) featuring the introduction of a C6 carboxyl group as novel HBV capsid inhibitors. This new series of 4-H HAPs showed improved anti-HBV activity and better drug-like properties compared to the first- and second-generation 4-H HAPs. X-ray crystallographic study of.analogue 12 (HAP_iR01) with Cp149 Y132A mutant hexamer clearly elucidated the role of C6 carboxyl group played for the increased binding affinity, which formed strong hydrogen' onding interactions with capsid protein and coordinated waters. The representative analogue 10 (HAP_R10) was extensively characterized in vitro (ADMET) and in vivo (mouse PK and PD) and subsequently selected for further devehipffientas oral anti-HBV infection agent.

  DOI：

  10.1021/acs.jmedchem.7b00083
• 作为产物：
  描述：

  3(R)-4-(2-chloro-4-fluorophenyl)-6-methyl-2-(2-thiazolyl)-1,4-dihydropyrimidine-5-carboxylic acid trifluoroethyl ester 在 Daicel Chiralpak IC, 30 mm × 250 mm, 5 μm 作用下， 生成 trifluoroethyl (R)-4-(2-chloro-4-fluorophenyl)-6-methyl-2-(2-thiazolyl)-1,4-dihydropyrimidin-5-carboxylate 、
  参考文献：
  名称：

  Discovery and Pre-Clinical Characterization of Third-Generation 4-H Heteroaryldihydropyrimidine (HAP) Analogues as Hepatitis B Virus (HBV) Capsid Inhibitors

  摘要：

  Described herein are the discovery and structure activity relationship (SAR) studies of the third-generation 4-H heteroaryldihydropyrimidines (4-H HAPs) featuring the introduction of a C6 carboxyl group as novel HBV capsid inhibitors. This new series of 4-H HAPs showed improved anti-HBV activity and better drug-like properties compared to the first- and second-generation 4-H HAPs. X-ray crystallographic study of.analogue 12 (HAP_iR01) with Cp149 Y132A mutant hexamer clearly elucidated the role of C6 carboxyl group played for the increased binding affinity, which formed strong hydrogen' onding interactions with capsid protein and coordinated waters. The representative analogue 10 (HAP_R10) was extensively characterized in vitro (ADMET) and in vivo (mouse PK and PD) and subsequently selected for further devehipffientas oral anti-HBV infection agent.

  DOI：

  10.1021/acs.jmedchem.7b00083

文献信息

• OPTICALLY PURE DIHYDROPYRIMIDINE COMPOUNDS AND THEIR USES FOR THE PREPARATION OF A MEDICAMENT FOR TREATMENT AND PREVENTION OF VIRAL DISEASES.
  申请人：Beijing Molecule Science and Technology Co., Ltd.

  公开号：EP2048141B1

  公开（公告）日：2017-06-14
• US8329902B2
  申请人：——

  公开号：US8329902B2

  公开（公告）日：2012-12-11
• Discovery and Pre-Clinical Characterization of Third-Generation 4-H Heteroaryldihydropyrimidine (HAP) Analogues as Hepatitis B Virus (HBV) Capsid Inhibitors
  作者：Zongxing Qiu、Xianfeng Lin、Weixing Zhang、Mingwei Zhou、Lei Guo、Buelent Kocer、Guolong Wu、Zhisen Zhang、Haixia Liu、Houguang Shi、Buyu Kou、Taishan Hu、Yimin Hu、Mengwei Huang、S. Frank Yan、Zhiheng Xu、Zheng Zhou、Ning Qin、Yue Fen Wang、Shuang Ren、Hongxia Qiu、Yuxia Zhang、Yi Zhang、Xiaoyue Wu、Kai Sun、Sheng Zhong、Jianxun Xie、Giorgio Ottaviani、Yuan Zhou、Lina Zhu、Xiaojun Tian、Liping Shi、Fang Shen、Yi Mao、Xue Zhou、Lu Gao、John A. T. Young、Jim Zhen Wu、Guang Yang、Alexander V. Mayweg、Hong C. Shen、Guozhi Tang、Wei Zhu

  DOI：10.1021/acs.jmedchem.7b00083

  日期：2017.4.27

  Described herein are the discovery and structure activity relationship (SAR) studies of the third-generation 4-H heteroaryldihydropyrimidines (4-H HAPs) featuring the introduction of a C6 carboxyl group as novel HBV capsid inhibitors. This new series of 4-H HAPs showed improved anti-HBV activity and better drug-like properties compared to the first- and second-generation 4-H HAPs. X-ray crystallographic study of.analogue 12 (HAP_iR01) with Cp149 Y132A mutant hexamer clearly elucidated the role of C6 carboxyl group played for the increased binding affinity, which formed strong hydrogen' onding interactions with capsid protein and coordinated waters. The representative analogue 10 (HAP_R10) was extensively characterized in vitro (ADMET) and in vivo (mouse PK and PD) and subsequently selected for further devehipffientas oral anti-HBV infection agent.