5-(2-Bromoethoxy)-6-fluoro-2-methylquinoline | 420786-96-5

• 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: 5-(2-Bromoethoxy)-6-fluoro-2-methylquinoline
• CAS: 420786-96-5
• 化学式: C₁₂H₁₁BrFNO
• 分子量: 284.128
• InChiKey: GHHKIAALQQIGMR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  22.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-(2-Bromoethoxy)-6-fluoro-2-methylquinoline 、 6-(哌啶-4-甲基)-2H-苯并[b][1,4]噁嗪-3(4h)-酮 在 N-ethyl-diisopropylethylamine 作用下， 以 异丙醇 为溶剂， 生成 6-[[1-[2-(6-fluoro-2-methylquinolin-5-yl)oxyethyl]piperidin-4-yl]methyl]-4H-1,4-benzoxazin-3-one
  参考文献：
  名称：

  3,4-Dihydro-2H-benzoxazinones as dual-acting 5-HT1A receptor antagonists and serotonin reuptake inhibitors

  摘要：

  Investigation of halogen substitution in lead compound 1 has led to the identification of analogues which combine high affinity for 5-HT1A receptors and potent serotonin reuptake inhibitory activity. Several compounds show an improved selectivity over 5-HT1B and 5-HT1D receptors and a superior pharmacokinetic profile in the rat. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.11.031
• 作为产物：
  描述：

  2-溴-4-氟-5-甲氧基苯胺 在 palladium on activated charcoal 盐酸 、 氢气 、 三溴化硼 、 potassium carbonate 作用下， 以 乙醇 、 二氯甲烷 、 丁酮 为溶剂， 生成 5-(2-Bromoethoxy)-6-fluoro-2-methylquinoline
  参考文献：
  名称：

  3,4-Dihydro-2H-benzoxazinones as dual-acting 5-HT1A receptor antagonists and serotonin reuptake inhibitors

  摘要：

  Investigation of halogen substitution in lead compound 1 has led to the identification of analogues which combine high affinity for 5-HT1A receptors and potent serotonin reuptake inhibitory activity. Several compounds show an improved selectivity over 5-HT1B and 5-HT1D receptors and a superior pharmacokinetic profile in the rat. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.11.031

文献信息

• Benzoxazinone derivatives, their preparation and use
  申请人：——

  公开号：US20040063704A1

  公开（公告）日：2004-04-01

  The present invention relates to novel compounds of formula (1) or a pharmaceutically acceptable salt thereof, wherein Ar is phenyl, naphthyl, a monocyclic heteroaromatic group or a bicyclic heteroaromatic group, said Ar group being optionally substituted by 1-4 substituents, which may be the same or different, and which are selected from the group consisting of: halogen, hydroxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, C 1-6 alkyl, trifluoromethanesulfonyloxy, pentafluoroethyl, C 1-6 alkoxy, arylC 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkoxyC 1-6 -alkyl, C 3-7 cycloalkylC 1-6 alkoxy, C 1-6 alkanoyl, C 1-6 alkoxycarbonyl, C 1-6 alkylsulfonyl, C 1-6 alkylsulfinyl, C 1-6 alkylsulfonyloxy, C 1-6 alkylsulfonylC 1-6 alkyl, arylsulfonyl, arylsulfonyloxy, arylsulfonylC 1-6 alkyl, C 1-6 alkylsulfonamido, C 1-6 alkylamido, C 1-6 alkylsulfonamidoC 1-6 alkyl, C 1-6 alkylamidoC 1-6 alkyl, arylsulfonamido, arylcarboxamido, arylsullonamidoC 1-6 alkyl, arylcarboxamidoC 1-6 alkyl, aroyl, arylC 1-6 alkyl, arylC 1-6 alkanoyl, a group R 3 OCO(CH 2 ) s , R 3 CON(R 4 )(CH 2 ) s , R 3 R 4 NCO(C 2 ) s or R 3 R 4 NSO 2 (CH 2 ) where each of R 3 and R 4 independently represents a hydrogen atom or C 1-4 alkyl or R 3 and R 4 form part of a C 1-6 azacyloalkane or C 3- 6 (2-oxo)azacycloalkane ring and s represents zero or an integer from 1 to 4, and a group Ar 1 Z, wherein Z represents a single bond, O, S or CH 2 and Ar 1 represents a phenyl or a monocyclic heteroaromatic group, said Ar 1 group being optionally substituted by 1-3 substituents, which may be the same or different, and which are selected from the group consisting of a halogen, hydroxy, cyano, trifluoromethyl, C 1-6 alkyl, C 1-6 alkoxy or C 1-6 alkanoyl; when Ar is a phenyl or a monocyclic heteroaromatic group, substitutents positioned ortho to one another may be linked to form a 5- or 6-membered ring: R 1 is hydrogen, C 1-6 alkyl, C 3-6 alkenyl, C 3-6 alkynyl or arylC 1-6 alkyl; R 2 is halogen, C 1-6 alkyl, cyano, CF 3 , C 1-6 alkanoyl, C 1-6 alkoxy or hydroxy; X is CH or N; Y is a single bond, O, or C═O; p is 0, 1 or 2; r is 0, 1, 2 or 3; m is 2, 3 or 4; n and q are independently 1 or 2. Processes for preparing the compounds, pharmaceutical compositions containing them and their use as medicaments for various CNS disorders, including deression and/or anxiety, are also disclosed.

  本发明涉及公式（1）的新化合物或其药学上可接受的盐，其中Ar是苯基，萘基，单环杂芳基或双环杂芳基，所述Ar基可以选择性地被1-4个取代基取代，这些取代基可以相同或不同，选自以下群组：卤素，羟基，氰基，硝基，三氟甲基，三氟甲氧基，C1-6烷基，三氟甲磺酰氧基，五氟乙基，C1-6烷氧基，芳基C1-6烷氧基，C1-6烷硫基，C1-6烷氧基C1-6烷基，C3-7环烷基C1-6烷氧基，C1-6酰基，C1-6烷氧羰基，C1-6烷基磺酰基，C1-6烷基亚磺基，C1-6烷基磺酰氧基，C1-6烷基磺酰基C1-6烷基，芳基磺酰基，芳基磺酰氧基，芳基磺酰基C1-6烷基，C1-6烷基磺酰胺基，C1-6烷基酰胺基，C1-6烷基磺酰胺基C1-6烷基，C1-6烷基酰胺基C1-6烷基，芳基磺酰胺基，芳基羧酰胺，芳基磺酰胺基C1-6烷基，芳基羧酰胺基C1-6烷基，酰基，芳基C1-6烷基，芳基C1-6酰基，一个R3OCO（CH2）s，R3CON（R4）（CH2）s，R3R4NCO（C2）s或R3R4NSO2（CH2）组，其中R3和R4各自独立地表示氢原子或C1-4烷基，或R3和R4构成C1-6氮杂环烷或C3-6（2-氧代）氮杂环烷环，s表示零或1-4的整数，以及一个Ar1Z基，其中Z表示单键，O，S或CH2，Ar1表示苯基或单环杂芳基，所述Ar1基可以选择性地被1-3个取代基取代，这些取代基可以相同或不同，选自以下群组：卤素，羟基，氰基，三氟甲基，C1-6烷基，C1-6烷氧基或C1-6酰基；当Ar是苯基或单环杂芳基时，相对位于一个环上的取代基可以连接形成5-或6-成员环；R1是氢，C1-6烷基，C3-6烯基，C3-6炔基或芳基C1-6烷基；R2是卤素，C1-6烷基，氰基，CF3，C1-6酰基，C1-6烷氧基或羟基；X是CH或N；Y是单键，O或C═O；p是0，1或2；r是0，1，2或3；m是2，3或4；n和q独立地为1或2。还公开了制备这些化合物的方法，包含它们的制药组合物以及它们作为治疗各种中枢神经系统疾病，包括抑郁和/或焦虑的药物的用途。
• BENZOXAZINONE DERIVATIVES, THEIR PREPARATION AND USE
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP1330460B1

  公开（公告）日：2007-03-21
• US6939871B2
  申请人：——

  公开号：US6939871B2

  公开（公告）日：2005-09-06
• [EN] BENZOXAZINONE DERIVATIVES, THEIR PREPARATION AND USE<br/>[FR] DERIVES DE BENZOXAZINONE, LEUR PREPARATION ET UTILISATION
  申请人：SMITHKLINE BEECHAM PLC

  公开号：WO2002034754A2

  公开（公告）日：2002-05-02

  The present invention relates to novel compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein Ar is phenyl, naphthyl, a monocyclic heteroaromatic group or a bicyclic heteroaromatic group, said Ar group being optionally substituted by 1-4 substituents, which may be the same or different, and which are selected from the group consisting of: halogen, hydroxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, C1-6alkyl, trifluoromethanesulfonyloxy, pentafluoroethyl, C1-6alkoxy, arylC1-6alkoxy, C1-6alkylthio, C1-6alkoxyC1-6alkyl, C3-7cycloalkylC1-6alkoxy, C1-6alkanoyl, C1-6alkoxycarbonyl, C1-6alkylsulfonyl, C1-6alkylsulfinyl, C1-6alkylsulfonyloxy, C1-6alkylsulfonylC1-6alkyl, arylsulfonyl, arylsulfonyloxy, arylsulfonylC1-6alkyl, C1-6alkylsulfonamido, C1-6alkylamido, C1-6alkylsulfonamidoC1-6alkyl, C1-6alkylamidoC1-6alkyl, arylsulfonamido, arylcarboxamido, arylsulfonamidoC1-6alkyl, arylcarboxamidoC1-6alkyl, aroyl, aroylC1-6alkyl, arylC1-6alkanoyl, a group R3OCO(CH¿2?)s, R?3CON(R4)(CH¿2)s, R3R4NCO(CH¿2?)s or R?3R4NSO¿2(CH2) where each of R?3 and R4¿ independently represents a hydrogen atom or C¿1-4?alkyl or R?3 and R4¿ form part of a C¿3-?6azacyloalkane or C3-6(2-oxo)azacycloalkane ring and s represents zero or an integer from 1 to 4, and a group Ar?1¿ Z, wherein Z represents a single bond, O, S or CH¿2? and Ar?1¿ represents a pheyl or a monocyclic heteroaromatic group, said Ar1 group being optionally substituted by 1-3 substituents, which may be the same or different, and which are selected from the group consisting of a halogen, hydroxy, cyano, trifluoromethyl, C¿1-6?alkyl, C1-6alkoxy or C1-6alkanoyl; when Ar is a phenyl or a monocyclic heteroaromatic group, substitutens positioned ortho to one another may be linked to form a 5- or 6-membered ring; R?1¿ is hydrogen, C¿1-6?alkyl, C3-6alkenyl, C3-6alkynyl or arylC1-6alkyl; R?2¿ is halogen, C¿1-6?alkyl, cyano, CF3, C1-6alkanoyl, C1-6alkoxy or hydroxy; X is CH or N; Y is a single bond, O, or C=O; p is 0, 1 or 2; r is 0, 1, 2 or 3; m is 2, 3 or 4; n and q are independently 1 or 2. Processes for preparing the compounds, pharmaceutical compositions containing them and their use as medicaments for various CNS disorders, including deression and/or anxiety, are also disclosed.
• 3,4-Dihydro-2H-benzoxazinones as dual-acting 5-HT1A receptor antagonists and serotonin reuptake inhibitors
  作者：Peter J. Lovell、Frank E. Blaney、Caroline J. Goodacre、Claire M. Scott、Paul W. Smith、Kathryn R. Starr、Kevin M. Thewlis、Antonio K.K. Vong、Simon E. Ward、Jeannette M. Watson

  DOI：10.1016/j.bmcl.2006.11.031

  日期：2007.2

  Investigation of halogen substitution in lead compound 1 has led to the identification of analogues which combine high affinity for 5-HT1A receptors and potent serotonin reuptake inhibitory activity. Several compounds show an improved selectivity over 5-HT1B and 5-HT1D receptors and a superior pharmacokinetic profile in the rat. (c) 2006 Elsevier Ltd. All rights reserved.