6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]-4-[(3,4,5-trimethoxyphenyl)amino]quinoline-3-carbonitrile

• 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: 6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]-4-[(3,4,5-trimethoxyphenyl)amino]quinoline-3-carbonitrile
• 英文别名: 6-Methoxy-7-[(1-methylpiperidine-4-yl)methoxy]-4-[(3,4,5-trimethoxyphenyl)amino]-3-quinolinecarbonitrile；4-Phenylamino-3-quinolinecarbonitrile 19；6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]-4-(3,4,5-trimethoxyanilino)quinoline-3-carbonitrile
• 化学式: C₂₇H₃₂N₄O₅
• 分子量: 492.575
• InChiKey: BWLSIYJKVFXNFV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  98.1
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  香草酸甲酯 在 palladium on activated charcoal 正丁基锂 、 甲酸 、 氢气 、 硝酸 、 吡啶盐酸盐 、 potassium carbonate 、 三氟乙酸 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]-4-[(3,4,5-trimethoxyphenyl)amino]quinoline-3-carbonitrile
  参考文献：
  名称：

  Investigation of the effect of varying the 4-anilino and 7-alkoxy groups of 3-quinolinecarbonitriles on the inhibition of Src kinase activity

  摘要：

  Several 7-alkoxy-4-anilino-3-quinolinecarbonitriles were synthesized and evaluated for Src kinase inhibitory activity. Optimal inhibition of both Src enzymatic and cellular activity was seen with analogues having a 2,4-dichloro-5-methoxyaniline group at C-4. Compound 18, which has a 1-methylpiperidinemethoxy group at C-7, showed in vivo activity in a xenograft model. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.07.001

文献信息

• [EN] 4-ANILINO-3-QUINOLINECARBONITRILES FOR THE TREATMENT OF CHRONIC MYELOGENOUS LEUKEMIA (CML)<br/>[FR] 4-ANILINO-3-QUINOLINECARBONITRILES DESTINES AU TRAITEMENT DE LEUCEMIE MYELOGENE CHRONIQUE (CML)
  申请人：WYETH CORP

  公开号：WO2005047259A1

  公开（公告）日：2005-05-26

  Compounds of the formula (I): wherein: n is an integer from 0-3; X is N, CH; R is alkyl of 1 to 3 carbon atoms; R' is 2,4-diCl, 5-OMe in para, ortho, or meta position; 2,4-diCl in para position; 3,4,5­tri-OMe in para position; 2-Cl, 5-OMe in para position; 2-Me, 5-OMe in para position; 2,4-di-Me in para position; 2,4-diMe-5-OMe in para position; 2,4-diCl, 5-OEt in para position; and R2 is alkyl of 1 to 3 carbon atoms, and pharmaceutically acceptable salts thereof.

  式(I)的化合物：其中：n是0-3之间的整数；X是N，CH；R是1至3个碳原子的烷基；R'是对位、邻位或间位的2,4-二氯，5-甲氧基；对位的2,4-二氯；对位的3,4,5-三甲氧基；对位的2-氯，5-甲氧基；对位的2-甲基，5-甲氧基；对位的2,4-二甲基；对位的2,4-二甲基-5-甲氧基；对位的2,4-二氯，5-乙氧基；以及R2是1至3个碳原子的烷基，及其药用可接受的盐。
• Process for the preparation of 7-substituted-3 quinolinecarbonitriles
  申请人：Wyeth Holdings Corporation

  公开号：US20030212276A1

  公开（公告）日：2003-11-13

  There is provided a process for the preparation of 7-substituted-3-quinolinecarbonitriles and intermediates useful in a process to prepare 7-substituted-3-quinolinecarbonitriles and pharmaceutically acceptable salts is described. Where 7-fluoro-4-oxo-1,4-dihydro-3-quinolinecarbonitrile is converted in three steps to 7-substituted-3-quinolinecarbonitriles which inhibit the action of certain protein kinases and are useful in the treatment of cancer.

  提供了一种制备7-取代-3-喹啉羰基腈和中间体的方法，该中间体在制备7-取代-3-喹啉羰基腈和药用可接受盐的过程中有用。将7-氟-4-氧代-1,4-二氢-3-喹啉羰基腈转化为7-取代-3-喹啉羰基腈，经过三个步骤，这些化合物抑制某些蛋白激酶的作用，并在癌症治疗中有用。
• 4-anilino-3-quinolinecarbonitriles for the treatment of chronic myelogenous leukemia (CML)
  申请人：Boschelli Frank

  公开号：US20050101780A1

  公开（公告）日：2005-05-12

  Compounds of the formula: wherein: n is an integer from 1-3; X is N, CH, provided that when X is N, n is 2 or 3; R is alkyl of 1 to 3 carbon atoms; R 1 is 2,4-diCl, 5-OMe; 2,4-diCl; 3,4,5-tri-OMe; 2-Cl, 5-OMe; 2-Me, 5-OMe; 2,4-di-Me; 2,4-diMe-5-OMe, 2,4-diCl, 5-OEt; R 2 is alkyl of 1 to 2 carbon atoms, and pharmaceutically acceptable salts thereof.

  化合物的公式为：其中：n为1-3的整数；X为N，CH，当X为N时，n为2或3；R为1至3个碳原子的烷基；R1为2,4-二氯，5-甲氧基；2,4-二氯；3,4,5-三甲氧基；2-氯，5-甲氧基；2-甲基，5-甲氧基；2,4-二甲基；2,4-二甲基-5-甲氧基，2,4-二氯，5-乙氧基；R2为1至2个碳原子的烷基，以及其药学上可接受的盐。
• TREATMENT OF IMATINIB RESISTANT LEUKEMIA
  申请人：Hewes Becker

  公开号：US20080318971A1

  公开（公告）日：2008-12-25

  The present invention provides 4-anilino-3-quinolinecarbonitriles compounds useful for treating a subject having an BcrAbl positive leukemia that is resistant to imatinib.

  本发明提供了4-苯胺基-3-喹啉羧腈化合物，用于治疗对伊马替尼具有抗性的BcrAbl阳性白血病患者。
• [EN] PROCESS FOR THE PREPARATION OF 7-SUBSTITUTED-3-QUINOLINE AND 3-QUINOL-4-ONE CARBONITRILES<br/>[FR] PREPARATION DE 3-QUINOLINE ET DE 3-QUINOL- 4-ONE CARBONITRILES SUBSTITUES EN POSITION 7
  申请人：WYETH CORP

  公开号：WO2003093241A1

  公开（公告）日：2003-11-13

  There is provided a process for the preparation of 7-substituted-3-quinolinecarbonitriles and intermediates useful in a process to prepare 7-substituted-3-quinolinecarbonitriles and pharmaceutically acceptable salts is described. Where 7-fluoro-4-oxo-1,4-dihydro-3-quinolinecarbonitrile is converted in three steps to 7-substituted-3-quinolinecarbonitriles which inhibit the action of certain protein kinases and are useful in the treatment of cancer.

  提供了一种制备7-取代-3-喹啉羰基腈及其中间体的方法，该中间体可用于制备7-取代-3-喹啉羰基腈及其药用可接受盐的方法。其中，7-氟-4-氧代-1,4-二氢-3-喹啉羰基腈经过三步转化成为抑制某些蛋白激酶作用且用于治疗癌症的7-取代-3-喹啉羰基腈。