oxazole-2-carboximidamide hydrochloride | 1571216-65-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: oxazole-2-carboximidamide hydrochloride
• 英文别名: 2-Oxazolecarboximidamide, hydrochloride；1,3-oxazole-2-carboximidamide;hydrochloride
• CAS: 1571216-65-3
• 化学式: C₄H₅N₃O*ClH
• 分子量: 147.564
• InChiKey: ZBHFWFPCUUZWPF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.38
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  75.9
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-甲氧基(全氟基-2-甲基-1-丙烯) 、 oxazole-2-carboximidamide hydrochloride 在 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 以50.5 %的产率得到6-fluoro-4-methoxy-2-(2-oxazolyl)-5-(trifluoromethyl)pyrimidine
  参考文献：
  名称：

  WO2022/202537

  摘要：

  公开号：
• 作为产物：
  描述：

  2-噁唑甲腈 在 sodium methylate 、 氯化铵 作用下， 以 甲醇 为溶剂， 反应 3.0h， 生成 oxazole-2-carboximidamide hydrochloride
  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

• Design, Synthesis, and Evaluation of Tetrahydropyrrolo[1,2-<i>c</i>]pyrimidines as Capsid Assembly Inhibitors for HBV Treatment
  作者：Xiaolin Li、Kai Zhou、Haiying He、Qiong Zhou、Ya Sun、Lijuan Hou、Liang Shen、Xiaofei Wang、Yuedong Zhou、Zhen Gong、Shibo He、Huangtao Jin、Zhengxian Gu、Shuyong Zhao、Long Zhang、Chunyan Sun、Shansong Zheng、Zhe Cheng、Yidong Zhu、Minghui Zhang、Jian Li、Shuhui Chen

  DOI：10.1021/acsmedchemlett.7b00288

  日期：2017.9.14

  The discovery of novel tetrahydropyrrolo[1,2-c]pyrimidines derivatives from Bay41_4109 as hepatitis B virus (HBV) inhibitors is herein reported. The structure–activity relationship optimization led to one highly efficacious compound 28a (IC50 = 10 nM) with good PK profiles and the favorite L/P ratio. The hydrodynamic injection model in mice clearly demonstrated the efficacy of 28a against HBV replication

  本文报道了来自Bay41_4109的新型四氢吡咯并[1,2- c ]嘧啶衍生物作为乙型肝炎病毒(HBV)抑制剂的发现。构效关系优化产生了一种高效化合物28a (IC 50 = 10 nM)，具有良好的 PK 特性和最受欢迎的 L/P 比。小鼠的水动力注射模型清楚地证明了28a对抗 HBV 复制的功效。
• DIHYDROPYRIMIDINE COMPOUNDS AND THEIR APPLICATION IN PHARMACEUTICALS
  申请人：SUNSHINE LAKE PHARMA CO., LTD.

  公开号：US20150152096A1

  公开（公告）日：2015-06-04

  Provided herein are dihydropyrimidine compounds and their pharmaceutical applications, especially for use in treating and preventing HBV diseases. Specifically, provided herein are compounds having Formula (I) or (Ia), or an enantiomer, a diastereoisomer, a tautomer, a hydrate, a solvate, or a pharmaceutically acceptable salt thereof, wherein the variables of the formulas are as defined in the specification. Also provided herein is the use of the compounds having Formula (I) or (Ia), or an enantiomer, a diastereoisomer, a tautomer, a hydrate, a solvate, or a pharmaceutically acceptable salt thereof for treating and preventing HBV diseases.

  本文提供了二氢嘧啶化合物及其药物应用，特别是用于治疗和预防乙型肝炎疾病。具体而言，本文提供了具有公式（I）或（Ia）的化合物，或其对映体、非对映异构体、互变异构体、水合物、溶剂物或其药学上可接受的盐，其中公式的变量如规范中所定义。本文还提供了使用具有公式（I）或（Ia）的化合物，或其对映体、非对映异构体、互变异构体、水合物、溶剂物或其药学上可接受的盐治疗和预防乙型肝炎疾病的方法。
• Dihydropyrimidine compounds and their application in pharmaceuticals
  申请人：SUNSHINE LAKE PHARMA CO., LTD.

  公开号：US09340538B2

  公开（公告）日：2016-05-17

  Provided herein are dihydropyrimidine compounds and their pharmaceutical applications, especially for use in treating and preventing HBV diseases. Specifically, provided herein are compounds having Formula (I) or (Ia), or an enantiomer, a diastereoisomer, a tautomer, a hydrate, a solvate, or a pharmaceutically acceptable salt thereof, wherein the variables of the formulas are as defined in the specification. Also provided herein is the use of the compounds having Formula (I) or (Ia), or an enantiomer, a diastereoisomer, a tautomer, a hydrate, a solvate, or a pharmaceutically acceptable salt thereof for treating and preventing HBV diseases.

  本文提供了二氢嘧啶化合物及其药物应用，特别是用于治疗和预防乙型肝炎疾病。具体而言，本文提供了具有式（I）或（Ia）的化合物，或其对映体、非对映异构体、互变异构体、水合物、溶剂化物或其药学上可接受的盐，其中式中的变量如规范中所定义。本文还提供了使用具有式（I）或（Ia）的化合物，或其对映体、非对映异构体、互变异构体、水合物、溶剂化物或其药学上可接受的盐来治疗和预防乙型肝炎疾病。
• 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.
• WO2022/202537
  申请人：——

  公开号：——

  公开（公告）日：——