4-hydroxy-7-methoxy-8-methyl-quinoline | 872497-14-8

• 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: 4-hydroxy-7-methoxy-8-methyl-quinoline
• 英文别名: 4-Quinolinol, 7-methoxy-8-methyl-；7-methoxy-8-methyl-1H-quinolin-4-one
• CAS: 872497-14-8
• 化学式: C₁₁H₁₁NO₂
• 分子量: 189.214
• InChiKey: AQGGIDFODMQYMY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-hydroxy-7-methoxy-8-methyl-quinoline 在 三氯氧磷 作用下， 生成 4-chloro-7-methoxy-8-methylquinoline
  参考文献：
  名称：

  Structure–activity relationship study on a novel series of cyclopentane-containing macrocyclic inhibitors of the hepatitis C virus NS3/4A protease leading to the discovery of TMC435350

  摘要：

  SAR analysis performed with a limited set of cyclopentane-containing macrocycles led to the identification of N-[17-[2-(4-isopropylthiazole-2-yl)-7-methoxy-8-methylquinolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diazatricyclo [13.3.0.0(4,6)]octadec-7-ene-4-carbonyl](cyclopropyl) sulfonamide (TMC435350, 32c) as a potent inhibitor of HCV NS3/4A protease (K-i = 0.36 nM) and viral replication (replicon EC50 = 7.8 nM). TMC435350 also displayed low in vitro clearance and high permeability, which were confirmed by in vivo pharmacokinetic studies. TMC435350 is currently being evaluated in the clinics. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.07.088
• 作为产物：
  描述：

  7-甲氧基-8-甲基-4-氧代-1H-喹啉-3-羧酸乙酯 在 sodium hydroxide 、 水 、 盐酸 作用下， 以 二苯醚 为溶剂， 反应 2.5h， 以96%的产率得到4-hydroxy-7-methoxy-8-methyl-quinoline
  参考文献：
  名称：

  WO2007/14926

  摘要：

  公开号：

文献信息

• [EN] HEPATITIS C INHIBITOR PEPTIDE ANALOGS<br/>[FR] ANALOGUES PEPTIDIQUES D'INHIBITEURS DE L'HEPATITE C
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2006000085A1

  公开（公告）日：2006-01-05

  The invention relates to compounds of formula (I) wherein R', R2, R3, R4, R5, R6, Y, n and m are as defined herein. The compounds are useful for the treatment and prevention of hepatitis C viral infections in mammals by inhibiting HCV NS3 protease. The invention further relates to azalactone compounds of the formula (III) which can be reacted with an amide anion to produce the compounds of formula (I).

  本发明涉及式(I)的化合物，其中R'，R2，R3，R4，R5，R6，Y，n和m如本文所述定义。这些化合物通过抑制HCV NS3蛋白酶，用于治疗和预防哺乳动物中的丙型肝炎病毒感染。本发明进一步涉及可以与酰胺阴离子反应以产生式(I)化合物的azalactone化合物（III）。
• [EN] HEPATITIS C INHIBITOR DIPEPTIDE ANALOGS<br/>[FR] ANALOGUES DIPEPTIDIQUES D'INHIBITEURS DE L'HEPATITE C
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2006007700A1

  公开（公告）日：2006-01-26

  The present invention relates to compounds of formula (I): wherein R1, R2, R4, n and m are as defined herein and R3 is selected from: (i) -C(O)OR31 wherein R31 is (C1-6)alkyl or aryl, wherein the (C1-6)alkyl is optionally substituted with one to three halogen substituents; (ii) -C(O)NR32R33, wherein R32 and R33 are each independently selected form H, (C1-6)alkyl, and Het; (iii) -SOvR34, wherein v is 1 or 2 and R34 is selected from: (C1-6)alkyl, aryl, Het, and NR32R33 wherein R32 and R33 are as defined above; and (iv) -CO(O)-R35, wherein R35 is selected from (C1-8)alkyl, (C3-7)cycloalkyl-(C1-4)alkyl, aryl, aryl-(C1-6)alkyl, Het and Het-(C1-6)alkyl, each of which are optionally substituted with one or more substituents each independently selected from halo, (C1-6)alkyl, (C3-7)cycloalkyl, aryl, Het, hydroxyl, -O-(C1-6)alkyl, -S-(C1-6)alkyl, -SO-(C1-6)alkyl, -SO2-(C1-6)alkyl, -O-aryl, -S-aryl, -SO-aryl and -SO2-aryl, wherein the aryl portion of the -O-aryl, -S-aryl, -SO-aryl and -SO2-aryl are each optionally substituted with one to five halo substituents. The present invention further relates to pharmaceutical compositions containing the compounds of formula (I) and methods for using these analogs in the treatment of HCV infection.

  本发明涉及以下式(I)的化合物：其中R1、R2、R4、n和m如本文所定义，R3选自：(i)-C(O)OR31，其中R31为(C1-6)烷基或芳基，其中(C1-6)烷基可选择地用一到三个卤素取代基取代；(ii)-C(O)NR32R33，其中R32和R33各自独立地选自H、(C1-6)烷基和Het；(iii)-SOvR34，其中v为1或2，R34选自：(C1-6)烷基、芳基、Het和NR32R33，其中R32和R33如上所定义；和(iv)-CO(O)-R35，其中R35选自(C1-8)烷基、(C3-7)环烷基-(C1-4)烷基、芳基、芳基-(C1-6)烷基、Het和Het-(C1-6)烷基，每种均可选择地用一种或多种取代基取代，每种取代基各自独立地选自卤素、(C1-6)烷基、(C3-7)环烷基、芳基、Het、羟基、-O-(C1-6)烷基、-S-(C1-6)烷基、-SO-(C1-6)烷基、-SO2-(C1-6)烷基、-O-芳基、-S-芳基、-SO-芳基和-SO2-芳基，其中-O-芳基、-S-芳基、-SO-芳基和-SO2-芳基的芳基部分可选择地用一到五个卤素取代基取代。本发明还涉及含有式(I)化合物的药物组合物以及在治疗HCV感染中使用这些类似物的方法。
• Hepatitis C inhibitor peptide analogs
  申请人：Bailey D. Murray

  公开号：US20060019905A1

  公开（公告）日：2006-01-26

  Compounds of formula (I): wherein R 1 , R 2 , R 3 , R 4 , R 5 , Y, n and m are as defined herein. The compounds are useful as inhibitors of HCV NS3 protease.

  式（I）的化合物：其中R1、R2、R3、R4、R5、Y、n和m的定义如本文所述。这些化合物可用作HCV NS3蛋白酶的抑制剂。
• Hepatitis C inhibitor dipeptide analogs
  申请人：Bailey D. Murray

  公开号：US20060046965A1

  公开（公告）日：2006-03-02

  Compounds of formula (I): wherein R 1 , R 2 , R 3 , R 4 , n and m are as defined herein. The compounds are useful as inhibitors of HCV NS3 protease.

  式(I)的化合物：其中R1、R2、R3、R4、n和m的定义如本文所述。这些化合物可用作HCV NS3蛋白酶的抑制剂。
• Hepatitis c inhibitor peptide analogs
  申请人：Bailey D. Murray

  公开号：US20060258868A1

  公开（公告）日：2006-11-16

  The invention relates to compounds of formula (I) wherein R′, R 2 , R 3 , R 4 , R 5 , R 6 , Y, n and m are as defined (herein. The compounds are useful for the treatment and prevention of hepatitis C viral infections in mammals by inhibiting HCV NS3 protease. The invention further relates to azalactone compounds of the formula (III) which can be reacted with an amide anion to produce the compounds of formula (I).

  本发明涉及到式(I)的化合物，其中R′、R2、R3、R4、R5、R6、Y、n和m的定义如本文中所述。这些化合物通过抑制HCV NS3蛋白酶对哺乳动物中的丙型肝炎病毒感染的治疗和预防具有用处。本发明还涉及到式(III)的氮杂内酰亚胺化合物，可以与酰胺阴离子反应，从而产生式(I)的化合物。