4-羟基-8-异丙基-3-喹啉羧酸 | 63136-17-4

• 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
• 中文名称: 4-羟基-8-异丙基-3-喹啉羧酸
• 英文名称: 8-isopropyl-4(1H)-quinolinone-3-carboxylic acid
• 英文别名: 8-Isopropyl-1,4-dihydro-quinoline；8-isopropyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid；4-Hydroxy-8-(propan-2-yl)quinoline-3-carboxylic acid；4-oxo-8-propan-2-yl-1H-quinoline-3-carboxylic acid
• CAS: 63136-17-4
• 化学式: C₁₃H₁₃NO₃
• mdl: MFCD05228468
• 分子量: 231.251
• InChiKey: KGDOGYITTVCUJA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-羟基-8-异丙基-3-喹啉羧酸 在 氯化亚砜 、 potassium carbonate 作用下， 以 水 、 丙酮 为溶剂， 反应 2.0h， 生成 4-chloro-8-propan-2-yl-N-prop-2-enylquinoline-3-carboxamide
  参考文献：
  名称：

  作为一类新型的胃H + / K + -ATPase抑制剂，合成了4-（苯基氨基）喹啉-3-羧酰胺。

  摘要：

  为了寻找胃H + / K + -ATP酶的抑制剂，合成了4-（苯氨基）喹啉-3-羧酰胺并评估了其对组胺诱导的大鼠胃酸分泌的抗分泌活性。这些化合物是通过将苯胺衍生物与N-取代的4-氯喹啉-3-羧酰胺缩合而合成的，后者是由亚硫酰氯处理4（1H）-喹啉酮-3-羧酸而获得的。大多数化合物抑制大鼠中组胺诱导的胃酸分泌。其中，N-烯丙基-4-（2-乙基苯基氨基）喹啉-3-羧酰胺（4h）是最有效的抑制剂，并且作为候选抗溃疡药的分布最佳。该化合物显示出可逆的K +竞争性胃H + / K + -ATPase抑制活性。

  DOI：

  10.1248/cpb.43.693
• 作为产物：
  描述：

  2-异丙基苯胺 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 9.0h， 生成 4-羟基-8-异丙基-3-喹啉羧酸
  参考文献：
  名称：

  作为一类新型的胃H + / K + -ATPase抑制剂，合成了4-（苯基氨基）喹啉-3-羧酰胺。

  摘要：

  为了寻找胃H + / K + -ATP酶的抑制剂，合成了4-（苯氨基）喹啉-3-羧酰胺并评估了其对组胺诱导的大鼠胃酸分泌的抗分泌活性。这些化合物是通过将苯胺衍生物与N-取代的4-氯喹啉-3-羧酰胺缩合而合成的，后者是由亚硫酰氯处理4（1H）-喹啉酮-3-羧酸而获得的。大多数化合物抑制大鼠中组胺诱导的胃酸分泌。其中，N-烯丙基-4-（2-乙基苯基氨基）喹啉-3-羧酰胺（4h）是最有效的抑制剂，并且作为候选抗溃疡药的分布最佳。该化合物显示出可逆的K +竞争性胃H + / K + -ATPase抑制活性。

  DOI：

  10.1248/cpb.43.693

文献信息

• Evaluation of 3-Carboxy-4(1<i>H</i>)-quinolones as Inhibitors of Human Protein Kinase CK2
  作者：Andriy G. Golub、Olexander Ya. Yakovenko、Volodymyr G. Bdzhola、Vladislav M. Sapelkin、Piotr Zien、Sergiy M. Yarmoluk

  DOI：10.1021/jm050048t

  日期：2006.11.1

  Due to the emerging role of protein kinase CK2 as a molecule that participates not only in the development of some cancers but also in viral infections and inflammatory failures, small organic inhibitors of CK2, besides application in scientific research, may have therapeutic significance. In this paper, we present a new class of CK2 inhibitorss3-carboxy-4(1H)-quinolones. This class of inhibitors has been selected via receptor-based virtual screening of the Otava compound library. It was revealed that the most active compounds, 5,6,8-trichloro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (7) (IC50 = 0.3 mu M) and 4-oxo-1,4-dihydrobenzo[h] quinoline-3-carboxylic acid (9) (IC50 = 1 AM), are ATP competitive (K-i values are 0.06 and 0.28 mu M, respectively). Evaluation of the inhibitors on seven protein kinases shows considerable selectivity toward CK2. According to theoretical calculations and experimental data, a structural model describing the key features of 3-carboxy-4(1H)-quinolones responsible for tight binding to CK2 active site has been developed.
• 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.
• Synthesis of 4-(Phenylamino)quinoline-3-carboxamides as a Novel Class of Gastric H+/K+-ATPase Inhibitors.
  作者：Minoru UCHIDA、Kenji OTSUBO、Jun MATSUBARA、Tadaaki OHTANI、Seiji MORITA、Katsuya YAMASAKI

  DOI：10.1248/cpb.43.693

  日期：——

  In search for inhibitors of gastric H+/K+-ATPase, 4-(phenylamino)quinoline-3-carboxamides were synthesized and evaluated for antisecretory activity against histamine-induced gastric acid secretion in rats. These compounds were synthesized by condensation of aniline derivatives with N-substituted 4-chloroquinoline-3-carboxamides, which were obtained from treatment of 4(1H)-quinolinone-3-carboxylic acid

  为了寻找胃H + / K + -ATP酶的抑制剂，合成了4-（苯氨基）喹啉-3-羧酰胺并评估了其对组胺诱导的大鼠胃酸分泌的抗分泌活性。这些化合物是通过将苯胺衍生物与N-取代的4-氯喹啉-3-羧酰胺缩合而合成的，后者是由亚硫酰氯处理4（1H）-喹啉酮-3-羧酸而获得的。大多数化合物抑制大鼠中组胺诱导的胃酸分泌。其中，N-烯丙基-4-（2-乙基苯基氨基）喹啉-3-羧酰胺（4h）是最有效的抑制剂，并且作为候选抗溃疡药的分布最佳。该化合物显示出可逆的K +竞争性胃H + / K + -ATPase抑制活性。