2-carbomethoxy-8-fluoro-4-hydroxy-7-methoxyquinoline | 801282-88-2

• 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: 2-carbomethoxy-8-fluoro-4-hydroxy-7-methoxyquinoline
• 英文别名: methyl 8-fluoro-7-methoxy-4-oxo-1H-quinoline-2-carboxylate
• CAS: 801282-88-2
• 化学式: C₁₂H₁₀FNO₄
• 分子量: 251.214
• InChiKey: ZTDHRVTUFPCAHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-carbomethoxy-8-fluoro-4-hydroxy-7-methoxyquinoline 、 N-[(cyclopentyloxy)carbonyl]-3-methyl-L-valyl-(4S)-N-[(1R,2S)-2-ethenyl-1-(methoxycarbonyl)cyclopropyl]-4-hydroxy-L-prolinamide 在 caesium carbonate 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 7.0h， 生成 methyl 4-[(3R,5S)-1-[(2S)-2-(cyclopentyloxycarbonylamino)-3,3-dimethylbutanoyl]-5-[[(1R,2S)-2-ethenyl-1-methoxycarbonylcyclopropyl]carbamoyl]pyrrolidin-3-yl]oxy-8-fluoro-7-methoxyquinoline-2-carboxylate
  参考文献：
  名称：

  Discovery of a Potent and Selective Noncovalent Linear Inhibitor of the Hepatitis C Virus NS3 Protease (BI 201335)

  摘要：

  C-Terminal carboxylic acid containing inhibitors of the NS3 protease are reported. A novel series of linear tripeptide inhibitors that are very potent and selective against the NS3 protease are described. A substantial contribution to the potency of these linear inhibitors arises from the introduction of a C8 substituent on the B-ring of the quinoline moiety found on the P2 of these inhibitors. The introduction of a CS methyl group results not only in a modest increase in the cell-based potency of these inhibitors but more importantly in a much better pharmacokinetic profile in rats as well. Exploration of C8-substitutions led to the identification of the bromo derivative as the best group at this position, resulting in a significant increase in the cell-based potency of this class of inhibitors. Structure activity studies on the C8-bromo derivatives ultimately led to the discovery of clinical candidate 29 (BI 201335), a very potent and selective inhibitor of genotypel NS3 protease with a promising PK profile in rats.

  DOI：

  10.1021/jm100690x
• 作为产物：
  描述：

  dimethyl 2-(2-fluoro-3-methoxyanilino)but-2-enedioate 以 二苯醚 为溶剂， 生成 2-carbomethoxy-8-fluoro-4-hydroxy-7-methoxyquinoline
  参考文献：
  名称：

  Discovery of a Potent and Selective Noncovalent Linear Inhibitor of the Hepatitis C Virus NS3 Protease (BI 201335)

  摘要：

  C-Terminal carboxylic acid containing inhibitors of the NS3 protease are reported. A novel series of linear tripeptide inhibitors that are very potent and selective against the NS3 protease are described. A substantial contribution to the potency of these linear inhibitors arises from the introduction of a C8 substituent on the B-ring of the quinoline moiety found on the P2 of these inhibitors. The introduction of a CS methyl group results not only in a modest increase in the cell-based potency of these inhibitors but more importantly in a much better pharmacokinetic profile in rats as well. Exploration of C8-substitutions led to the identification of the bromo derivative as the best group at this position, resulting in a significant increase in the cell-based potency of this class of inhibitors. Structure activity studies on the C8-bromo derivatives ultimately led to the discovery of clinical candidate 29 (BI 201335), a very potent and selective inhibitor of genotypel NS3 protease with a promising PK profile in rats.

  DOI：

  10.1021/jm100690x

文献信息

• [EN] HEPATITIS C INHIBITOR COMPOUNDS<br/>[FR] COMPOSES INHIBITEURS DE L'HEPATITE C
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2004103996A1

  公开（公告）日：2004-12-02

  Compounds of formula (I): wherein B, X, R3, L0, L1, L2, R2, R1 and RC are defined herein. The compounds are useful as inhibitors of HCV NS3 protease for the treatment of hepatitis C viral infection.

  公式（I）的化合物：其中B、X、R3、L0、L1、L2、R2、R1和RC的定义如本文所述。这些化合物可用作丙型肝炎病毒NS3蛋白酶的抑制剂，用于治疗丙型肝炎病毒感染。
• Hepatitis C inhibitor compounds
  申请人：Llinas-Brunet Montse

  公开号：US20050020503A1

  公开（公告）日：2005-01-27

  Compounds of formula (I): wherein B, X, R 3 , L 0 , L 1 , L 2 , R 2 , R 1 and R C are defined herein. The compounds are useful as inhibitors of HCV NS3 protease for the treatment of hepatitis C viral infection.

  式（I）的化合物：其中B、X、R3、L0、L1、L2、R2、R1和RC的定义如下。这些化合物可用作HCV NS3蛋白酶的抑制剂，用于治疗丙型肝炎病毒感染。
• Hepatitis C Inhibitor Compounds
  申请人：LLINAS-BRUNET Montse

  公开号：US20070243166A1

  公开（公告）日：2007-10-18

  Compounds of formula (I): wherein B, X, R 3 , L 0 , L 1 , L 2 , R 2 , R 1 and R C are defined herein. The compounds are useful as inhibitors of HCV NS3 protease for the treatment of hepatitis C viral infection.

  式(I)的化合物：其中B、X、R3、L0、L1、L2、R2、R1和RC的定义如下。该化合物可用作HCV NS3蛋白酶的抑制剂，用于治疗丙型肝炎病毒感染。
• MACROCYCLIC PEPTIDES ACTIVE AGAINST THE HEPATITIS C VIRUS
  申请人：LLINAS-BRUNET Montse

  公开号：US20100028300A1

  公开（公告）日：2010-02-04

  Compounds of formula I: wherein D, R 4 , R 3 , L 0 , L 1 , L 2 , R 2 and R C are defined herein; or a pharmaceutically acceptable salt thereof, useful as inhibitors of the HCV NS3 protease.

  式子I的化合物：其中D，R4，R3，L0，L1，L2，R2和RC在此定义；或其药学上可接受的盐，用作HCV NS3蛋白酶的抑制剂。
• HEPATITIS C INHIBITOR COMPOUNDS
  申请人：Boehringer Ingelheim International GmbH

  公开号：EP1654261B1

  公开（公告）日：2007-11-14