ethyl 4-oxo-1-(4-(trifluoromethoxy)benzyl)-1,4-dihydroquinoline-3-carboxylate | 1207748-62-6

• 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-oxo-1-(4-(trifluoromethoxy)benzyl)-1,4-dihydroquinoline-3-carboxylate
• 英文别名: Ethyl 4-oxo-1-[[4-(trifluoromethoxy)phenyl]methyl]quinoline-3-carboxylate
• CAS: 1207748-62-6
• 化学式: C₂₀H₁₆F₃NO₄
• 分子量: 391.347
• InChiKey: DHYJGPONFILKOQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  ethyl 4-oxo-1-(4-(trifluoromethoxy)benzyl)-1,4-dihydroquinoline-3-carboxylate 在 水 、 sodium hydroxide 作用下， 反应 2.0h， 以61%的产率得到4-oxo-1-(4-(trifluoromethoxy)benzyl)-1,4-dihydroquinoline-3-carboxylic acid
  参考文献：
  名称：

  [EN] AGENTS FOR USE IN THE TREATMENT OF CARDIOVASCULAR AND INFLAMMATORY DISEASES STRUCTURALLY BASED ON 4(1 H)-QUINOLONE
  [FR] AGENTS DESTINÉS À ÊTRE UTILISÉS DANS LE TRAITEMENT DE MALADIES CARDIOVASCULAIRES ET INFLAMMATOIRES AYANT UNE STRUCTURE BASÉE SUR LA 4(1H)-QUINOLONE

  摘要：

  本发明提供了一种式I的化合物，其互变异构体，或其药用可接受的盐或N-氧化物，用于治疗或预防心血管疾病或炎症性疾病或症状。

  公开号：

  WO2015189560A1
• 作为产物：
  描述：

  苯胺 在 potassium carbonate 作用下， 以 二苯醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 38.5h， 生成 ethyl 4-oxo-1-(4-(trifluoromethoxy)benzyl)-1,4-dihydroquinoline-3-carboxylate
  参考文献：
  名称：

  [EN] AGENTS FOR USE IN THE TREATMENT OF CARDIOVASCULAR AND INFLAMMATORY DISEASES STRUCTURALLY BASED ON 4(1 H)-QUINOLONE
  [FR] AGENTS DESTINÉS À ÊTRE UTILISÉS DANS LE TRAITEMENT DE MALADIES CARDIOVASCULAIRES ET INFLAMMATOIRES AYANT UNE STRUCTURE BASÉE SUR LA 4(1H)-QUINOLONE

  摘要：

  本发明提供了一种式I的化合物，其互变异构体，或其药用可接受的盐或N-氧化物，用于治疗或预防心血管疾病或炎症性疾病或症状。

  公开号：

  WO2015189560A1

文献信息

• Agents for use in the treatment of cardiovascular and inflammatory diseases structurally based on 4(1 H)-quinolone
  申请人：UCL Business PLC

  公开号：US10087144B2

  公开（公告）日：2018-10-02

  The present invention provides a compound of formula I, a tautomer thereof, or a pharmaceutically acceptable salt or N-oxide thereof for use in the treatment or prevention of cardiovascular disease or of an inflammatory disease or condition: wherein: V is N or CR3; X is N or CR4; Y is N or CR5; Z is N or CR6; B is —(C═O)R1, a 5- to 10-membered heteroaryl group, or a group L′″-NRR′, wherein R and R′ are the same or different and each represents a hydrogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group; R1 is a 5- to 10-membered heterocyclyl group, or —OR′, wherein R′ is a hydrogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group, or R1 is a proteinogenic α amino acid, which is linked to the carbonyl moiety in the compound of formula (I) via the α amino group, which amino acid is optionally esterified at the α carboxylic acid group with a C1-C6 alkyl group or a C6-C10 aryl group, or R1 is —NR″R′″, —NRIV-L′″-CONR″R′″, or —NRIV-L′″-COOR, wherein R, R″, R′″ and RIV are the same or different and each represents a hydrogen atom, a C1-C6 alkyl group or a C1-C6 haloalkyl group; either (a) W is N and R9 and R2 together form a bond, or (b) W is CR8, R8 and R9 together form a bond and R2 is a hydrogen atom, or a C1-C6 alkyl, C1-C6 haloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocyclyl, -L′-A2, C3-C10 cycloalkyl, or —COOR′ group, wherein R′ is a hydrogen atom or C1-C6 alkyl group, or, when Z is a moiety CR6, R2 may form, together with R6 and the carbon and nitrogen atoms which connect R2 and R6 in the formula (I), a 5- to 6-membered heterocyclic ring; R3 is a hydrogen atom, a halogen atom, or a hydroxy, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, nitro, or —NR′R″ group, wherein R′ and R″ are the same or different and each represent a hydrogen atom or C1-C6 alkyl group; R4 and R5 are the same or different and each represent a hydrogen atom, a halogen atom, or a hydroxyl, C1-C8 alkyl, C1-C8 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, nitro, —NR′R″, —CO2R′″, C6-C10 aryl, 5- to 10-membered heteroaryl, 5 to 10-membered heterocyclyl, or —CO—(C1-C6 alkyl) group, wherein R′, R″ and R′″ are the same or different and each represent a hydrogen atom or C1-C6 alkyl group, or R4 and R5 and the carbon atoms bonded to R4 and R5 together form a 5- to 6-membered heterocyclic ring; R6 is a hydrogen atom, a halogen atom, or a C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy or —CO2R′ group, wherein R′ is hydrogen or C1-C6 alkyl, or, when W is a moiety CR8, R6 may form, together with R2 and the carbon and nitrogen atoms which connect R6 and R2 in the formula (I), a 5- to 6-membered heterocyclic ring; R7 is a hydrogen atom, a halogen atom, or a C1-C6 alkyl, or C1-C6 haloalkyl group, A2 represents a C6-C10 aryl or 5- to 10-membered heteroaryl group; L′, and L′″ are the same or different and each represent a C1-C6 alkylene, C2-C6 alkenylene, or C2-C6 alkynylene group; said aryl, heteroaryl, cycloalkyl and heterocyclyl groups being unsubstituted or substituted with one or more substituents selected from halogen, hydroxy, C1-C4 alkyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, —SOR, —SO2R, —NR′R″, —NR′(C═O)R″, —COOR, nitro and cyano substituents, wherein R, R′ and R″ are the same or different and each represents a hydrogen atom or C1-C4 alkyl group.

  本发明提供了一种式 I 的化合物、其同系物或其药学上可接受的盐或 N-氧化物，用于治疗或预防心血管疾病或炎症性疾病或病症： 其中： V 是 N 或 CR3 X 是 N 或 CR4 Y 是 N 或 CR5 Z 是 N 或 CR6； B 是-(C═O)R1、5 至 10 元杂芳基或一个基团 L′″-NRR′，其中R和R′相同或不同，各自代表氢原子、C1-C6烷基或C1-C6卤代烷基； R1 是 5 至 10 元杂环基，或 -OR′，其中 R′是氢原子、C1-C6 烷基或 C1-C6 卤代烷基，或 R1 是蛋白源 α 氨基酸，它通过 α 氨基与式（I）化合物中的羰基相连、R1是-NR″R′″、-NRIV-L′″-CONR″R′″或-NRIV-L′″-COOR，其中R、R″、R′″和RIV相同或不同，各自代表氢原子、C1-C6烷基或C1-C6卤代烷基； 或者 (a) W 是 N，R9 和 R2 一起形成键，或者 (b) W 是 CR8，R8 和 R9 一起形成键，R2 是氢原子，或者是 C1-C6 烷基、C1-C6 卤代烷基、C6-C10 芳基、5-至 10 元杂芳基、5-至 10 元杂环烷基、-L′-A2、C3-C10 环烷基、或-COOR′基团，其中 R′为氢原子或 C1-C6 烷基，或者当 Z 为 CR6 子团时，R2 可与 R6 以及连接式（I）中 R2 和 R6 的碳原子和氮原子一起形成 5 至 6 元杂环； R3 是氢原子、卤素原子或羟基、C1-C6 烷基、C1-C6 烷氧基、C1-C6 卤代烷基、C1-C6 卤代烷氧基、硝基或 -NR′R″ 基团，其中 R′ 和 R″ 相同或不同，且各自代表氢原子或 C1-C6 烷基； R4 和 R5 相同或不同，各自代表氢原子、卤素原子或羟基、C1-C8 烷基、C1-C8 卤代烷基、C1-C6 烷氧基、C1-C6 卤代烷氧基、硝基、-NR′R″、-CO2R′″、C6-C10 芳基、5-至 10 元杂芳基、5-至 10 元杂环基、或-CO-(C1-C6 烷基)基团，其中 R′、R″ 和 R′″ 相同或不同，且各自代表氢原子或 C1-C6 烷基，或 R4 和 R5 以及与 R4 和 R5 键合的碳原子共同形成 5 至 6 元杂环； R6 是氢原子、卤素原子或 C1-C6 烷基、C1-C6 卤代烷基、C1-C6 烷氧基、C1-C6 卤代烷氧基或 -CO2R′ 基团，其中 R′ 是氢或 C1-C6 烷基，或者当 W 是分子 CR8 时，R6 可与式 (I) 中的 R2 以及连接 R6 和 R2 的碳原子和氮原子一起形成 5 至 6 元杂环； R7 是氢原子、卤素原子或 C1-C6 烷基或 C1-C6 卤代烷基、 A2 代表 C6-C10 芳基或 5 至 10 元杂芳基； L′和 L′″相同或不同，各自代表 C1-C6 烯基、C2-C6 烯基或 C2-C6 炔基； C1-C4卤代烷基、C1-C4卤代烷氧基、-SOR、-SO2R、-NR′R″、-NR′(C═O)R″、-COOR、硝基和氰基取代基，其中 R、R′和 R″ 相同或不同，各自代表氢原子或 C1-C4 烷基。
• Parallel synthesis of N-biaryl quinolone carboxylic acids as selective M1 positive allosteric modulators
  作者：Feng V. Yang、William D. Shipe、Jaime L. Bunda、M. Brad Nolt、David D. Wisnoski、Zhijian Zhao、James C. Barrow、William J. Ray、Lei Ma、Marion Wittmann、Matthew A. Seager、Kenneth A. Koeplinger、George D. Hartman、Craig W. Lindsley

  DOI：10.1016/j.bmcl.2009.11.100

  日期：2010.1

  An iterative analog library synthesis approach was employed in the exploration of a quinolone carboxylic acid series of selective M-1 positive allosteric modulators, and strategies for improving potency and plasma free fraction were identified. (C) 2009 Elsevier Ltd. All rights reserved.
• AGENTS FOR USE IN THE TREATMENT OF CARDIOVASCULAR AND INFLAMMATORY DISEASES STRUCTURALLY BASED ON 4(1 H)-QUINOLONE
  申请人：UCL Business PLC

  公开号：US20170066722A1

  公开（公告）日：2017-03-09

  The present invention provides a compound of formula I, a tautomer thereof, or a pharmaceutically acceptable salt or N-oxide thereof for use in the treatment or prevention of cardiovascular disease or of an inflammatory disease or condition: wherein: V is N or CR 3 ; X is N or CR 4 ; Y is N or CR 5 ; Z is N or CR 6 ; B is —(C═O)R 1 , a 5- to 10-membered heteroaryl group, or a group -L′″-NRR′, wherein R and R′ are the same or different and each represents a hydrogen atom, a C 1 -C 6 alkyl group or a C 1 -C 6 haloalkyl group; R 1 is a 5- to 10-membered heterocyclyl group, or —OR′, wherein R′ is a hydrogen atom, a C 1 -C 6 alkyl group or a C 1 -C 6 haloalkyl group, or R 1 is a proteinogenic α amino acid, which is linked to the carbonyl moiety in the compound of formula (I) via the α amino group, which amino acid is optionally esterified at the α carboxylic acid group with a C 1 -C 6 alkyl group or a C 6 -C 10 aryl group, or R 1 is —NR″R′″, —NR IV -L′″-CONR″R′″, or —NR IV -L′″-COOR, wherein R, R″, R′″ and R IV are the same or different and each represents a hydrogen atom, a C 1 -C 6 alkyl group or a C 1 -C 6 haloalkyl group; either (a) W is N and R 9 and R 2 together form a bond, or (b) W is CR 8 , R 8 and R 9 together form a bond and R 2 is a hydrogen atom, or a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 6 -C 10 aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocyclyl, -L′-A 2 , C 3 -C 10 cycloalkyl, or —COOR′ group, wherein R′ is a hydrogen atom or C 1 -C 6 alkyl group, or, when Z is a moiety CR 6 , R 2 may form, together with R 6 and the carbon and nitrogen atoms which connect R 2 and R 6 in the formula (I), a 5- to 6-membered heterocyclic ring; R 3 is a hydrogen atom, a halogen atom, or a hydroxy, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, nitro, or —NR′R″ group, wherein R′ and R″ are the same or different and each represent a hydrogen atom or C 1 -C 6 alkyl group; R 4 and R 5 are the same or different and each represent a hydrogen atom, a halogen atom, or a hydroxyl, C 1 -C 8 alkyl, C 1 -C 8 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, nitro, —NR′R″, —CO 2 R′″, C 6 -C 10 aryl, 5- to 10-membered heteroaryl, 5 to 10-membered heterocyclyl, or —CO—(C 1 -C 6 alkyl) group, wherein R′, R″ and R′″ are the same or different and each represent a hydrogen atom or C 1 -C 6 alkyl group, or R 4 and R 5 and the carbon atoms bonded to R 4 and R 5 together form a 5- to 6-membered heterocyclic ring; R 6 is a hydrogen atom, a halogen atom, or a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy or —CO 2 R′ group, wherein R′ is hydrogen or C 1 -C 6 alkyl, or, when W is a moiety CR 8 , R 6 may form, together with R 2 and the carbon and nitrogen atoms which connect R 6 and R 2 in the formula (I), a 5- to 6-membered heterocyclic ring; R 7 is a hydrogen atom, a halogen atom, or a C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl group, A 2 represents a C 6 -C 10 aryl or 5- to 10-membered heteroaryl group; L′, and L′″ are the same or different and each represent a C 1 -C 6 alkylene, C 2 -C 6 alkenylene, or C 2 -C 6 alkynylene group; said aryl, heteroaryl, cycloalkyl and heterocyclyl groups being unsubstituted or substituted with one or more substituents selected from halogen, hydroxy, C 1 -C 4 alkyl, C 1 -C 4 hydroxyalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, —SOR, —SO 2 R, —NR′R″, —NR′(C═O)R″, —COOR, nitro and cyano substituents, wherein R, R′ and R″ are the same or different and each represents a hydrogen atom or C 1 -C 4 alkyl group.