4-氯-7-(2-氯乙氧基)-6-甲氧基-3-喹啉甲腈 | 214470-72-1

• 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-氯-7-(2-氯乙氧基)-6-甲氧基-3-喹啉甲腈
• 英文名称: 4-chloro-7-(2-chloroethoxy)-6-methoxy-3-quinolinecarbonitrile
• 英文别名: 7-(2-chloro-ethoxy)-4-chloro-6-methoxy-quinoline-3-carbonitrile；4-chloro-7-(2-chloroethoxy)-3-cyano-6-methoxyquinoline；4-chloro-7-(2-chloroethoxy)-6-methoxyquinoline-3-carbonitrile
• CAS: 214470-72-1
• 化学式: C₁₃H₁₀Cl₂N₂O₂
• 分子量: 297.141
• InChiKey: GAOYRWYHERKJQE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  55.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-氯-7-(2-氯乙氧基)-6-甲氧基-3-喹啉甲腈 在 sodium iodide 作用下， 以 乙二醇乙醚 、 乙二醇二甲醚 为溶剂， 生成 6-Methoxy-7-(2-morpholin-4-yl-ethoxy)-4-(4-phenoxy-phenylamino)-quinoline-3-carbonitrile
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationships of 3-Cyano-4-(phenoxyanilino)quinolines as MEK (MAPKK) Inhibitors

  摘要：

  A series of 3-cyano-4-(phenoxyanilino)cyanoquinolines has been prepared as MEK (MAP kinase kinase) inhibitors. The best activity is seen with alkoxy groups at both the 6- and 7-positions. The lead compounds show low nanomolar IC50's against MAP kinase kinase, and have potent inhibitory activity in tumor cells. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00580-1
• 作为产物：
  描述：

  香草酸甲酯 在 (C₈H₁₇)3N(CH₃)Cl 、 硝酸 、 铁粉 、 potassium carbonate 、 氯化铵 、 溶剂黄146 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 丙酮 为溶剂， 生成 4-氯-7-(2-氯乙氧基)-6-甲氧基-3-喹啉甲腈
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationships of 3-Cyano-4-(phenoxyanilino)quinolines as MEK (MAPKK) Inhibitors

  摘要：

  A series of 3-cyano-4-(phenoxyanilino)cyanoquinolines has been prepared as MEK (MAP kinase kinase) inhibitors. The best activity is seen with alkoxy groups at both the 6- and 7-positions. The lead compounds show low nanomolar IC50's against MAP kinase kinase, and have potent inhibitory activity in tumor cells. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00580-1

文献信息

• Substituted 3-cyano quinolines
  申请人：American Cyanamid Company

  公开号：US06002008A1

  公开（公告）日：1999-12-14

  This invention provides compounds having the formula: ##STR1## wherein: X is cycloalkyl which may be optionally substituted; or is a pyridinyl, pyrimidinyl, or phenyl ring; wherein the pyridinyl, pyrimidinyl, or phenyl ring may be optionally substituted; n is 0-1; Y is --NH--, --O--, --S--, or --NR--; R is alkyl of 1-6 carbon atoms; R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are each, independently, hydrogen, halogen, alkyl, alkenyl, alkynyl, alkenyloxy, alkynyloxy, hydroxymethyl, halomethyl, alkanoyloxy, alkenoyloxy, alkynoyloxy, alkanoyloxymethyl, alkenoyloxymethyl, alkynoyloxymethyl, alkoxymethyl, alkoxy, alkylthio, alkylsulphinyl, alkylsulphonyl, alkylsulfonamido, alkenylsulfonamido, alkynylsulfonamido, hydroxy, trifluoromethyl, cyano, nitro, carboxy, carboalkoxy, carboalkyl, phenoxy, phenyl, thiophenoxy, benzyl, amino, hydroxyamino, alkoxyamino, alkylamino, dialkylamino, aminoalkyl, N-alkylaminoalkyl, N,N-dialkylaminoalkyl, phenylamino, benzylamino, ##STR2## R.sub.5 is alkyl which may be optionally substituted, or phenyl which may be optionally substituted; R.sub.6 is hydrogen, alkyl, or alkenyl; R.sub.7 is chloro or bromo R.sub.8 is hydrogen, alkyl, aminoalkyl, N-alkylaminoalkyl, N,N-dialkylaminoalkyl, N-cycloalkylaminoalkyl, N-cycloalkyl-N-alkylaminoalkyl, N,N-dicycloalkylaminoalkyl, morpholino-N-alkyl, piperidino-N-alkyl, N-alkyl-piperidino-N-alkyl, azacycloalkyl-N-alkyl, hydroxyalkyl, alkoxyalkyl, carboxy, carboalkoxy, phenyl, carboalkyl+, chloro, fluoro, or bromo; Z is amino, hydroxy, alkoxy, alkylamino, dialkylamino, morpholino, piperazino, N-alkylpiperazino, or pyrrolidino; m=1-4,q=1-3, and p=0-3; any of the substituents R.sub.1, R.sub.2, R.sub.3, or R.sub.4 that are located on contiguous carbon atoms can together be the divalent radical --O--C(R.sub.8).sub.2 --O--; or a pharmaceutically acceptable salt thereof with the proviso that when Y is --NH--, R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are hydrogen, and n is 0, X is not 2-methylphenyl, which are inhibitors of protein tyrosine kinase.

  这项发明提供了具有以下结构的化合物：##STR1## 其中：X是环烷基，可以选择性地被取代；或者是吡啶基、嘧啶基或苯环；其中吡啶基、嘧啶基或苯环可以选择性地被取代；n为0-1；Y为--NH--、--O--、--S--或--NR--；R为1-6个碳原子的烷基；R.sub.1、R.sub.2、R.sub.3和R.sub.4分别独立地是氢、卤素、烷基、烯基、炔基、烯氧基、炔氧基、羟甲基、卤甲基、烷酰氧基、烯酰氧基、炔酰氧基、烷酰氧甲基、烯酰氧甲基、炔酰氧甲基、烷氧甲基、烷氧基、烷基硫、烷基亚砜基、烷基磺酰基、烷基磺酰胺基、烯基磺酰胺基、炔基磺酰胺基、羟基、三氟甲基、氰基、硝基、羧基、羧基烷氧基、羧基烷基、苯氧基、苯基、噻吩氧基、苄基、氨基、羟氨基、烷氧氨基、烷基氨基、二烷基氨基、氨基烷基、N-烷基氨基烷基、N,N-二烷基氨基烷基、苯基氨基、苄氨基、##STR2## R.sub.5是可以选择性取代的烷基，或者是可以选择性取代的苯基；R.sub.6是氢、烷基或烯基；R.sub.7是氯或溴；R.sub.8是氢、烷基、氨基烷基、N-烷基氨基烷基、N,N-二烷基氨基烷基、N-环烷基氨基烷基、N-环烷基-N-烷基氨基烷基、N,N-二环烷基氨基烷基、吗啉-N-烷基、哌啶-N-烷基、N-烷基-哌啶-N-烷基、氮杂环烷基-N-烷基、羟基烷基、烷氧基烷基、羧基、羧基烷氧基、苯基、羧基+、氯、氟或溴；Z是氨基、羟基、烷氧基、烷基氨基、二烷基氨基、吗啉基、哌嗪基、N-烷基哌嗪基或吡咯烷基；m=1-4，q=1-3，p=0-3；任何位于相邻碳原子上的R.sub.1、R.sub.2、R.sub.3或R.sub.4取代基可以共同形成二价基团--O--C(R.sub.8).sub.2 --O--；或其药学上可接受的盐，但当Y为--NH--时，R.sub.1、R.sub.2、R.sub.3和R.sub.4为氢，n为0时，X不是2-甲基苯基，这些化合物是蛋白酪氨酸激酶的抑制剂。
• Method of treating or inhibiting colonic polyps
  申请人：American Cyanamid Company

  公开号：US06384051B1

  公开（公告）日：2002-05-07

  This invention provides a method of treating or inhibiting colonic polyps which comprises providing a compound of formula 1 wherein: R1, R2, R3, R4, X, Y, and n are as defined hereinbefore, or a pharmaceutically acceptable salt thereof.

  本发明提供了一种治疗或抑制结肠息肉的方法，包括提供如下公式1的化合物： 其中： R1、R2、R3、R4、X、Y和n如前文所定义，或其药用可接受的盐。
• Substituted 3-cyanoquinolines
  申请人：American Cyanamid Company

  公开号：US06288082B1

  公开（公告）日：2001-09-11

  This invention provides compounds of formula I having the structure wherein G1, G2, R1, R4, Z, n, and X are defined in the specification or a pharmaceutically acceptable salt thereof which are useful as antineoplastic agents and in the treatment of polycystic kidney disease.

  这项发明提供了具有结构的化合物I的公式，其中G1、G2、R1、R4、Z、n和X在规范中定义，或其药用盐，这些化合物可用作抗肿瘤剂，并用于多囊肾病的治疗。
• [EN] 3-CYANO-QUINOLINE DERIVATIVES AS NON-RECEPTOR TYROSINE KINASE INHIBITORS<br/>[FR] DERIVES DE LA 3-CYANO-QUINOLEINE, EN TANT QU'INHIBITEURS DE TYROSINE KINASE NON RECEPTEURS
  申请人：ASTRAZENECA AB

  公开号：WO2004069249A1

  公开（公告）日：2004-08-19

  The invention concerns quinoline derivatives of: (Formula I) (A chemical formula should be inserted here - please see paper copy enclosed herewith) wherein Z is an O, S, SO, SO2, N(R2) or C(R2)(R3) group wherein each R2 or R3 group is hydrogen or (1-6C)alkyl, m is 1, 2 or 3, each R1 group is selected from halogeno, (1-6C)alkyl, (1-6C)alkoxy and any of the other meanings defined in the description, Ra is hydrogen or halogeno, Rb is hydrogen, halogeno, (1-6C)alkyl or (1-6C)alkoxy, Rc is (1-6C)alkoxy and Rd is hydrogen, halogeno, (1-6C)alkyl or (1-6C)alkoxy, or Rc and Rd together form a (1-3C)alkylenedioxy group, or pharmaceutically acceptable salts thereof; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an anti-invasive agent in the containment and/or treatment of solid tumour disease.

  该发明涉及喹啉衍生物：(化学式I) （此处应插入化学式 - 请参阅随函附上的纸质副本），其中Z为O、S、SO、SO2、N(R2)或C(R2)(R3)基团，其中每个R2或R3基团为氢或(1-6C)烷基，m为1、2或3，每个R1基团从卤代烷基、(1-6C)烷基、(1-6C)烷氧基和描述中定义的其他含义中选择，Ra为氢或卤代基，Rb为氢、卤代基、(1-6C)烷基或(1-6C)烷氧基，Rc为(1-6C)烷氧基，Rd为氢、卤代基、(1-6C)烷基或(1-6C)烷氧基，或Rc和Rd一起形成(1-3C)烷基二氧基基团，或其药学上可接受的盐；它们的制备方法，含有它们的药物组合物以及它们在制造用作抗侵袭剂的药物的用途中在固体肿瘤疾病的控制和/或治疗中的使用。
• 3-Quinolinecarbonitrile protein kinase inhibitors
  申请人：Berger Maarten Dan

  公开号：US20050187247A1

  公开（公告）日：2005-08-25

  This invention provides a compound of Formula 1 where Ar, X, R 1 , R 2 , R 3 , and R 4 are defined herein, or a pharmaceutically acceptable salt thereof useful in the prevention or inhibition of diseases associated with the Ras/Raf/MEK signaling cascade in a mammal, such as neoplasms, strokes, osteoporosis, cancer, rheumatoid arthritis, inflammatory disease, polycystic kidney disease, and colonic polyps, and methods of making the compounds of formula 1 and intermediates.

  该发明提供了一种化合物，其化学式为1，其中Ar、X、R1、R2、R3和R4的定义如下，或其药用盐，在哺乳动物体内用于预防或抑制与Ras/Raf/MEK信号级联相关的疾病，如肿瘤、中风、骨质疏松症、癌症、类风湿性关节炎、炎症性疾病、多囊性肾病和结肠息肉，以及制备化合物1和中间体的方法。