4-cyclopropyl-thiazole-2-carboxamidine | 1578155-76-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-cyclopropyl-thiazole-2-carboxamidine
• 英文别名: 4-cyclopropyl-thiazole-2-carboxamidine hydrochloride；4-cyclopropylthiazole-2-carboximidamide hydrochloride；4-Cyclopropyl-1,3-thiazole-2-carboximidamide;hydrochloride
• CAS: 1578155-76-6
• 化学式: C₇H₉N₃S*ClH
• 分子量: 203.696
• InChiKey: HYXBIJYALHVFMG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.73
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  91
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-cyclopropyl-thiazole-2-carboxamidine 在 N-溴代丁二酰亚胺(NBS) 、 potassium acetate 、 N,N-二异丙基乙胺 作用下， 以 四氯化碳 、 二氯甲烷 、 2,2,2-三氟乙醇 为溶剂， 反应 18.0h， 生成 (3S)-4-[[(4R)-4-(2-chloro-4-fluoro-phenyl)-2-(4-cyclopropylthiazol-2-yl)-5-methoxycarbonyl-1,4-dihydropyrimidin-6-yl]methyl]-morpholine-3-carboxylic acid
  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：

  2-溴-4-环丙基噻唑 在 sodium methylate 作用下， 以 甲醇 、 N,N-二甲基乙酰胺 为溶剂， 反应 6.0h， 生成 4-cyclopropyl-thiazole-2-carboxamidine
  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

• Potassium channel modulators
  申请人：Cadent Therapeutics, Inc.

  公开号：US10774064B2

  公开（公告）日：2020-09-15

  Provided are novel compounds of Formula (I): and pharmaceutically acceptable salts thereof, which are useful for treating a variety of diseases, disorders or conditions which can be affected by potassium channel modulation. Also provided are pharmaceutical compositions comprising the novel compounds of Formula (I), pharmaceutically acceptable salts thereof, and methods for their use in treating one or more diseases, disorders or conditions, associated with potassium channels.

  本发明提供了式 (I) 的新型化合物：及其药学上可接受的盐类，它们可用于治疗各种可受钾通道调节影响的疾病、失调或病症。还提供了包含式（I）新型化合物及其药学上可接受的盐的药物组合物，以及将其用于治疗一种或多种与钾通道相关的疾病、失调或病症的方法。
• POTASSIUM CHANNEL MODULATORS
  申请人：Cadent Therapeutics, Inc.

  公开号：US20190218200A1

  公开（公告）日：2019-07-18

  Provided are novel compounds of Formula (I): and pharmaceutically acceptable salts thereof, which are useful for treating a variety of diseases, disorders or conditions which can be affected by potassium channel modulation. Also provided are pharmaceutical compositions comprising the novel compounds of Formula (I), pharmaceutically acceptable salts thereof, and methods for their use in treating one or more diseases, disorders or conditions, associated with potassium channels.