ethyl 4-hydroxy-2-oxo-1-{[(1E)-phenylmethylidene]amino}-1,2-dihydro-3-quinolinecarboxylate | 931402-02-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: ethyl 4-hydroxy-2-oxo-1-{[(1E)-phenylmethylidene]amino}-1,2-dihydro-3-quinolinecarboxylate
• 英文别名: ethyl 4-hydroxy-2-oxo-1-{[phenylmethylene]amino}-1,2-dihydroquinoline-3-carboxylate；ethyl 1-[(E)-benzylideneamino]-4-hydroxy-2-oxoquinoline-3-carboxylate
• CAS: 931402-02-7
• 化学式: C₁₉H₁₆N₂O₄
• 分子量: 336.347
• InChiKey: JMXXCAFAVQCQMW-UDWIEESQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  79.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 4-hydroxy-2-oxo-1-{[(1E)-phenylmethylidene]amino}-1,2-dihydro-3-quinolinecarboxylate 在 氢氧化钾 作用下， 以 甲苯 为溶剂， 反应 21.5h， 生成 1-(benzylideneamino)-3-(1,1-dioxo-4H-1lambda6,2,4-benzothiadiazin-3-yl)-4-hydroxyquinolin-2-one
  参考文献：
  名称：

  Inhibitors of HCV NS5B polymerase: synthesis and structure–activity relationships of N-1-heteroalkyl-4-hydroxyquinolon-3-yl-benzothiadiazines

  摘要：

  N-1-Alkylamino and N-1-alkyloxy-4-hydroxyquinolon-3-yl benzothiadiazines were synthesized and evaluated as inhibitors of genotype 1 HCV polymerase. The N-1-alkyloxy derivatives were not potent inhibitors, however N-1-alkylamino derivatives displayed comparable potency to carbon analogs. Analogs with aliphatic substituents were significantly more potent than those with benzylic substituents against genotype la polymerase. The most potent inhibitors contained small alkyl or carbocyclic substituents and exhibited IC50's of 50-100 and 200-400 nM against genotype 1 b and 1 a HCV polymerase, respectively. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.01.071
• 作为产物：
  描述：

  2-肼基苯甲酸盐酸盐 在 sodium ethanolate 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 甲苯 为溶剂， 反应 20.0h， 生成 ethyl 4-hydroxy-2-oxo-1-{[(1E)-phenylmethylidene]amino}-1,2-dihydro-3-quinolinecarboxylate
  参考文献：
  名称：

  Inhibitors of HCV NS5B polymerase: synthesis and structure–activity relationships of N-1-heteroalkyl-4-hydroxyquinolon-3-yl-benzothiadiazines

  摘要：

  N-1-Alkylamino and N-1-alkyloxy-4-hydroxyquinolon-3-yl benzothiadiazines were synthesized and evaluated as inhibitors of genotype 1 HCV polymerase. The N-1-alkyloxy derivatives were not potent inhibitors, however N-1-alkylamino derivatives displayed comparable potency to carbon analogs. Analogs with aliphatic substituents were significantly more potent than those with benzylic substituents against genotype la polymerase. The most potent inhibitors contained small alkyl or carbocyclic substituents and exhibited IC50's of 50-100 and 200-400 nM against genotype 1 b and 1 a HCV polymerase, respectively. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.01.071

文献信息

• Anti-infective agents
  申请人：——

  公开号：US20040087577A1

  公开（公告）日：2004-05-06

  Compounds having the formula 1 are hepatitis C (HCV) polymerase inhibitors. Also disclosed are a composition and method for inhibiting hepatitis C (HCV) polymerase, processes for making the compounds, and synthetic intermediates employed in the processes.

  具有公式1的化合物是丙型肝炎（HCV）聚合酶抑制剂。还公开了一种用于抑制丙型肝炎（HCV）聚合酶的组成和方法，用于制造这些化合物的过程，以及在这些过程中使用的合成中间体。
• ANTI-INFECTIVE AGENTS
  申请人：Wagner Rolf

  公开号：US20080214528A1

  公开（公告）日：2008-09-04

  The present invention provides HCV polymerase inhibiting compounds having the formula (I): where R 1 is cyclobutyl—N(R a )-, n is 1, 2, 3 or 4, and at least one R 5 is R a SO 2 N(R j )alkyl-, In a non-limiting example, a compound of the present invention is N-[(3-1-[(cyclobutyl)amino])-4-hydroxy -2-oxo-1,2-dihydro-quinolin-3-yl}-1,1-dioxo-1,4-dihydro-1λ 6 -thieno[2,3-e][1,2,4]thiadiazin-7-yl)methyl]methane-sulfonamide. The present invention also features compositions comprising the compounds of the present invention or pharmaceutically acceptable salts, stereoisomers or tautomers thereof, and methods of using the same to treat or prevent HCV infection.

  本发明提供了具有以下式子（I）的HCV聚合酶抑制化合物：其中R1是环丁基-N（Ra）-，n为1、2、3或4，至少一个R5是RaSO2N（Rj）烷基-。在非限制性的例子中，本发明的化合物是N-[(3-1-[(环丁基)氨基])-4-羟基-2-氧代-1,2-二氢-喹啉-3-基}-1,1-二氧代-1,4-二氢-1λ6-噻吩[2,3-e][1,2,4]噻二嗪-7-基)甲基]甲磺酰胺。本发明还涉及包含本发明的化合物或其药学上可接受的盐、立体异构体或互变异构体的组合物，以及使用它们治疗或预防HCV感染的方法。
• Anti-Infective Agents
  申请人：Wagner Rolf

  公开号：US20100120753A1

  公开（公告）日：2010-05-13

  The present invention provides HCV polymerase inhibiting compounds having the formula (I): where R 1 is cyclobutyl-N(R a )—, n is 1, 2, 3 or 4, and at least one R 5 is R a SO 2 N(R j )alkyl-. In a non-limiting example, a compound of the present invention is N-[(3-1-[(cyclobutyl)amino]-4-hydroxy-2-oxo-1,2-dihydro-quinolin-3-yl}-1,1-dioxo-1,4-dihydro-1λ 6 -thieno[2,3-e][1,2,4]thiadiazin-7-yl)methyl]methane-sulfonamide. The present invention also features compositions comprising the compounds of the present invention or pharmaceutically acceptable salts, stereoisomers or tautomers thereof, and methods of using the same to treat or prevent HCV infection.

  本发明提供了具有以下式子(I)的HCV聚合酶抑制剂化合物：其中R1为环丁基-N(Ra)-，n为1、2、3或4，至少一个R5为RaSO2N(Rj)烷基-。在一个非限定性的例子中，本发明的一种化合物是N-[(3-1-[(环丁基)氨基]-4-羟基-2-氧代-1,2-二氢喹啉-3-基}-1,1-二氧代-1,4-二氢-1λ6-噻吩[2,3-e][1,2,4]噻二嗪-7-基)甲基]甲磺酰胺。本发明还涉及包含本发明化合物或其药学上可接受的盐、立体异构体或互变异构体的组合物，以及使用它们来治疗或预防HCV感染的方法。
• WO2007/38571
  申请人：——

  公开号：——

  公开（公告）日：——
• US7662958B2
  申请人：——

  公开号：US7662958B2

  公开（公告）日：2010-02-16