5-methyloxazole-4-carboxamidine | 1514661-23-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-methyloxazole-4-carboxamidine
• 英文别名: 5-Methyl-oxazole-4-carboxamidine；5-methyl-1,3-oxazole-4-carboximidamide
• CAS: 1514661-23-4
• 化学式: C₅H₇N₃O
• 分子量: 125.13
• InChiKey: OHDZSHZBOJRRAJ-UHFFFAOYSA-N

物化性质

• 沸点：
  234.7±42.0 °C(Predicted)
• 密度：
  1.41±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  75.9
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-methyloxazole-4-carboxamidine 在 N-溴代丁二酰亚胺(NBS) 、 potassium acetate 作用下， 以 四氯化碳 、 2,2,2-三氟乙醇 为溶剂， 反应 17.0h， 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：

  5-甲基噁唑-4-羧酸乙酯 在 三聚氯氰 、 氨 、 sodium methylate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 55.0h， 生成 5-methyloxazole-4-carboxamidine
  参考文献：
  名称：

  [EN] 6-AMINO ACID HETEROARYLDIHYDROPYRIMIDINES FOR THE TREATMENT AND PROPHYLAXIS OF HEPATITIS B VIRUS INFECTION
  [FR] HÉTÉROARYLDIHYDROPYRIMIDINES D'ACIDE 6-AMINÉ POUR LE TRAITEMENT ET LA PROPHYLAXIE D'UNE INFECTION PAR LE VIRUS DE L'HÉPATITE B

  摘要：

  这项发明提供了具有一般式的新化合物：其中R1、R2、R3、R4和A如本文所述，包括这些化合物的组合物以及使用这些化合物的方法。

  公开号：

  WO2014037480A1

文献信息

• Novel 6-amino acid heteroaryldihydropyrimidines for the treatment and prophylaxis of hepatitis B virus infection
  申请人：HOFFMANN-LA ROCHE INC.

  公开号：US20150031687A1

  公开（公告）日：2015-01-29

  The invention provides novel compounds having the general formula: wherein R 1 , R 2 , R 3 , R 4 and A are as described herein, compositions including the compounds and methods of using the compounds.

  这项发明提供了具有一般式的新化合物：其中R1、R2、R3、R4和A如本文所述，包括该化合物的组合物和使用该化合物的方法。
• [EN] 6-AMINO ACID HETEROARYLDIHYDROPYRIMIDINES FOR THE TREATMENT AND PROPHYLAXIS OF HEPATITIS B VIRUS INFECTION<br/>[FR] HÉTÉROARYLDIHYDROPYRIMIDINES D'ACIDE 6-AMINÉ POUR LE TRAITEMENT ET LA PROPHYLAXIE D'UNE INFECTION PAR LE VIRUS DE L'HÉPATITE B
  申请人：HOFFMANN LA ROCHE

  公开号：WO2014037480A1

  公开（公告）日：2014-03-13

  The invention provides novel compounds having the general formula:, wherein R1, R2, R3, R4 and A are as described herein, compositions including the compounds and methods of using the compounds.

  这项发明提供了具有一般式的新化合物：其中R1、R2、R3、R4和A如本文所述，包括这些化合物的组合物以及使用这些化合物的方法。
• NOVEL 6-AMINO ACID HETEROARYLDIHYDROPYRIMIDINES FOR THE TREATMENT AND PROPHYLAXIS OF HEPATITIS B VIRUS INFECTION
  申请人：HOFFMANN-LA ROCHE INC.

  公开号：US20160237078A9

  公开（公告）日：2016-08-18

  The invention provides novel compounds having the general formula: wherein R 1 , R 2 , R 3 , R 4 and A are as described herein, compositions including the compounds and methods of using the compounds.

  本发明提供了具有以下一般式的新化合物：其中R1，R2，R3，R4和A如本文所述，包括该化合物的组合物以及使用该化合物的方法。
• 6-amino acid heteroaryldihydropyrimidines for the treatment and prophylaxis of hepatitis B virus infection
  申请人：HOFFMANN-LA ROCHE INC.

  公开号：US09447086B2

  公开（公告）日：2016-09-20

  The invention provides novel compounds having the general formula: wherein R1, R2, R3, R4 and A are as described herein, compositions including the compounds and methods of using the compounds.

  该发明提供了具有以下一般式的新化合物：其中R1、R2、R3、R4和A如本文所述，包括该化合物的组合物和使用该化合物的方法。
• 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.