(S)-4-benzhydryl-9-hydroxy-2-(2-methoxyethyl)-1,8-dioxo-1,3,4,8-tetrahydro-2H-pyrido[1,2-a]pyrazine-7-carboxylic acid | 1370237-33-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-4-benzhydryl-9-hydroxy-2-(2-methoxyethyl)-1,8-dioxo-1,3,4,8-tetrahydro-2H-pyrido[1,2-a]pyrazine-7-carboxylic acid
• 英文别名: (4S)-4-benzhydryl-9-hydroxy-2-(2-methoxyethyl)-1,8-dioxo-3,4-dihydropyrido[1,2-a]pyrazine-7-carboxylic acid
• CAS: 1370237-33-4
• 化学式: C₂₅H₂₄N₂O₆
• 分子量: 448.475
• InChiKey: UUYKVUDGRPBNTO-LJQANCHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (S)-4-benzhydryl-9-(benzyloxy)-2-(2-methoxyethyl)-1,8-dioxo-1,3,4,8-tetrahydro-2H-pyrido[1,2-a]pyrazine-7-carboxylic acid 在 三氟乙酸 作用下， 反应 1.0h， 以92%的产率得到(S)-4-benzhydryl-9-hydroxy-2-(2-methoxyethyl)-1,8-dioxo-1,3,4,8-tetrahydro-2H-pyrido[1,2-a]pyrazine-7-carboxylic acid
  参考文献：
  名称：

  氨基甲酰基吡啶酮自行车衍生物作为流行性感冒帽依赖性核酸内切酶的强抑制剂的合成及SAR研究。

  摘要：

  公开了作为氨基甲酸酯帽依赖性核酸内切酶（CEN）抑制剂的一系列新的氨基甲酰基吡啶酮自行车（CAB）化合物的药物化学和结构-活性关系（SAR）。使用对接研究在CAB环系统的C（N）-1，N-3和C-7位置评估了取代基的作用。使用C-7未取代的CAB在细胞分析中获得亚微摩尔EC50值，该CAB在C-1或N-1位置均具有苯甲基。发现N-3取代基对于体外血浆蛋白结合作用至关重要，并且CAB-N类似物2v表现出合理的总清除率（CLtot）。更重要的是，化合物2v在感染流感病毒的小鼠模型中显示出显着的功效。

  DOI：

  10.1021/acs.jmedchem.9b00861

文献信息

• SUBSTITUTED POLYCYCLIC CARBAMOYL PYRIDONE DERIVATIVE PRODRUG
  申请人：Takahashi Chika

  公开号：US20130197219A1

  公开（公告）日：2013-08-01

  The present invention provides a compound having antiviral effects, particularly having growth inhibitory activity on influenza viruses, a preferred example of the compound being a substituted 3-hydroxy-4-pyridone derivative prodrug having cap-dependent endonuclease inhibitory activity.

  本发明提供了一种具有抗病毒效果的化合物，特别是对流感病毒具有生长抑制活性，该化合物的首选例子是一种具有依赖帽端核酸酶抑制活性的取代3-羟基-4-吡啶酮衍生物前药。
• Substituted polycyclic carbamoyl pyridone derivative prodrug
  申请人：Shionogi & Co., Ltd.

  公开号：US10202379B2

  公开（公告）日：2019-02-12

  The present invention provides a compound having antiviral effects, particularly having growth inhibitory activity on influenza viruses, a preferred example of the compound being a substituted 3-hydroxy-4-pyridone derivative prodrug having cap-dependent endonuclease inhibitory activity.

  本发明提供了一种具有抗病毒作用，特别是对流感病毒具有生长抑制活性的化合物，该化合物的一个优选实例是具有帽依赖性内切酶抑制活性的取代 3-羟基-4-吡啶酮衍生物原药。
• Arenavirus growth inhibitor comprising polycyclic carbamoylpyridone derivative
  申请人：NATIONAL UNIVERSITY CORPORATION HOKKAIDO UNIVERSITY

  公开号：US11492352B2

  公开（公告）日：2022-11-08

  The present invention provides a compound having antiviral activity, especially having arenavirus proliferation inhibitory activity, and/or a medicament comprising the compound. More preferably, the present invention provides a compound having proliferation inhibitory activity on the Old World arenaviruses such as Luna virus, Lassa virus, and lymphocytic choriomeningitis virus and/or the New World arenaviruses such as Junin virus, and/or a medicament comprising the compound. An arenavirus proliferation inhibitor comprising a compound represented by Formula (I) or a prodrug thereof or a pharmaceutically acceptable salt thereof: (wherein R1 is carboxy, or the like; A3 is CR2 or N; R2 is a hydrogen atom, halogen, hydroxy, or the like; R3 is a hydrogen atom, hydroxy, carboxy, cyano, formyl, alkyl optionally substituted with Substituent group F, or the like; either A1 or A2 is CR6R6, and the other is NR7, or A1 is CR8R9, and A2 is CR10R11; and R5, R6, R7, R8, R9, R10, and R11 are each independently a hydrogen atom, carboxy, cyano, alkyl optionally substituted with Substituent group F, or the like).

  本发明提供了一种具有抗病毒活性的化合物，尤其是具有抑制禽流感病毒增殖活性的化合物，和/或包含该化合物的药物。更优选地，本发明提供了一种化合物，该化合物对旧大陆病毒（如卢纳病毒、拉萨病毒和淋巴细胞色素膜炎病毒）和/或新大陆病毒（如朱宁病毒）具有增殖抑制活性，和/或包含该化合物的药物。 一种由式（I）代表的化合物或其原药或其药学上可接受的盐组成的腺病毒增殖抑制剂： (其中 R1 是羧基或类似物；A3 是 CR2 或 N；R2 是氢原子、卤素、羟基或类似物；R3 是氢原子、羟基、羧基、氰基、甲酰基、任选被取代基 F 取代的烷基或类似物；A1 或 A2 是 CR6R6，另一个是 NR7，或 A1 是 CR8R9，A2 是 CR10R11；以及 R5、R6、R7、R8、R9、R10 和 R11 各自独立地是氢原子、羧基、氰基、任选被取代基 F 取代的烷基或类似基团）。
• PRODRUG SUBSTITUTED POLYCYCLIC CARBAMOYL PYRIDONE DERIVATIVE
  申请人：Shionogi & Co., Ltd.

  公开号：US20200339565A1

  公开（公告）日：2020-10-29

  The present invention provides a compound having antiviral effects, particularly having growth inhibitory activity on influenza viruses, a preferred example of the compound being a substituted 3-hydroxy-4-pyridone derivative prodrug having cap-dependent endonuclease inhibitory activity.
• ARENAVIRUS GROWTH INHIBITOR COMPRISING POLYCYCLIC CARBAMOYL PYRIDONE DERIVATIVE
  申请人：NATIONAL UNIVERSITY CORPORATION HOKKAIDO UNIVERSITY

  公开号：US20210292321A1

  公开（公告）日：2021-09-23

  The present invention provides a compound having antiviral activity, especially having arenavirus proliferation inhibitory activity, and/or a medicament comprising the compound. More preferably, the present invention provides a compound having proliferation inhibitory activity on the Old World arenaviruses such as Luna virus, Lassa virus, and lymphocytic choriomeningitis virus and/or the New World arenaviruses such as Junin virus, and/or a medicament comprising the compound. An arenavirus proliferation inhibitor comprising a compound represented by Formula (I) or a prodrug thereof or a pharmaceutically acceptable salt thereof: (wherein R 1 is carboxy, or the like; A 3 is CR 2 or N; R 2 is a hydrogen atom, halogen, hydroxy, or the like; R 3 is a hydrogen atom, hydroxy, carboxy, cyano, formyl, alkyl optionally substituted with Substituent group F, or the like; either A 1 or A 2 is CR 6 R 6 , and the other is NR 7 , or A 1 is CR 8 R 9 , and A 2 is CR 10 R 11 ; and R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are each independently a hydrogen atom, carboxy, cyano, alkyl optionally substituted with Substituent group F, or the like).