6-{1-[2-(7,8-Difluoro-2-methyl-quinolin-5-yloxy)-ethyl]-piperidin-4-ylmethyl}-4H-benzo[1,4]oxazin-3-one | 420786-08-9

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 6-{1-[2-(7,8-Difluoro-2-methyl-quinolin-5-yloxy)-ethyl]-piperidin-4-ylmethyl}-4H-benzo[1,4]oxazin-3-one
• 英文别名: 6-[[1-[2-(7,8-difluoro-2-methylquinolin-5-yl)oxyethyl]piperidin-4-yl]methyl]-4H-1,4-benzoxazin-3-one
• CAS: 420786-08-9
• 化学式: C₂₆H₂₇F₂N₃O₃
• 分子量: 467.515
• InChiKey: BNMODWYXWORWHQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  63.7
• 氢给体数：
  1
• 氢受体数：
  7

文献信息

• [EN] HETEROCYCLIC COMPOUNDS POSSESSING AFFINITY AT 5HT1-TYPE RECEPTORS AND USE THEREOF IN THERAPY<br/>[FR] COMPOSES PRESENTANT UNE AFFINITE AVEC DES RECEPTEURS DE TYPE 5HT1 ET LEUR UTILISATION THERAPEUTIQUE
  申请人：GLAXO GROUP LTD

  公开号：WO2003068772A1

  公开（公告）日：2003-08-21

  Compounds of formula (I) and pharmaceutically acceptable salts thereof are disclosed:(I)wherein A is optionally substituted phenyl, naphthyl, indolyl, quinolinyl, quinazolinyl, indazolyl, isoquinolinyl or benzofuranyl; b is 1, 2 or 3 and c is 1, 2 or 3, wherein b + c is 2, 3, 4 or 5; X is carbon, Y is CH, is a double bond and e is 0; or X is carbon, Y is CH2 or oxygen, is a single bond and e is 1; or X is nitrogen, Y is CH2, is a single bond and e is 0; R1 is hydrogen, cyano, halogen, C1-6alkyl, C1-6alkoxy, C1-6alkoxyC1-6alkyl, NHCOCH3 or OCONR5R6, wherein R5 and R6 are independently hydrogen or C1-6alkyl; R2 is halogen, cyano or C1-6alkoxy; d is 0, 1, 2 or 3; R3 is hydrogen, C1-6alkyl, C1-6alkanoyl, fluoroC1-6alkanoyl, C1-6alkylsulfonyl, fluoroC1-6alkylsulfonyl, carbamoyl, C1-6alkylcarbamoyl or arylC1-6alkyl; and R4, together with the nitrogen atom to which it is attached, forms an optionally substituted 5 to 7 membered heterocyclic group fused to the benzene ring, provided that when a compound of formula (I) has the following structure: wherein A, b, c, R1, e, X, Y, R2 and d are as defined above and R3 is hydrogen, C1-6alkyl or arylC1-6alkyl, then (i) X is carbon, Y is CH and is a double bond; or (ii) b and c are both 1; or (iii) the carbon atom adjacent to the oxo-substituted carbon atom in the morpholinyl ring, marked ' * ', is substituted. Methods of preparing the compounds and uses of the compounds in therapy, in particular for a CNS disorder such as depression or anxiety, are also disclosed.

  公开了式(I)的化合物及其药学上可接受的盐： (I)其中A是可选择取代的苯基、萘基、吲哚基、喹啉基、喹唑啉基、吲唑基、异喹啉基或苯并呋喃基；b为1、2或3，c为1、2或3，其中b+c为2、3、4或5；X为碳，Y为CH，为双键，e为0；或X为碳，Y为CH2或氧，为单键，e为1；或X为氮，Y为 ，为单键，e为0；R1为氢、氰基、卤素、C1-6烷基、C1-6烷氧基、C1-6烷氧基C1-6烷基、NHCOCH3或OCONR5R6，其中R5和R6各自独立地为氢或C1-6烷基；R2为卤素、氰基或C1-6烷氧基；d为0、1、2或3；R3为氢、C1-6烷基、C1-6酰基、氟代C1-6酰基、C1-6烷基磺酰基、氟代C1-6烷基磺酰基、氨基甲酰基、C1-6烷基氨基甲酰基或芳基C1-6烷基；而当式(I)的化合物具有以下结构时：其中A、b、c、R1、e、X、Y、R2和d如上定义，而R3为氢、C1-6烷基或芳基C1-6烷基时，(i) X为碳，Y为CH，为双键；或(ii) b和c均为1；或(iii)在吗啉环中氧代取代的碳原子相邻的碳原子，标记为'*'，被取代。还公开了制备这些化合物的方法以及这些化合物在治疗中的用途，特别是在中枢神经系统紊乱如抑郁症或焦虑症中的用途。
• Heterocyclic compounds possessing affinity at 5ht1-type receptors and use thereof in therapy
  申请人：Harrington P Frank

  公开号：US20050085458A1

  公开（公告）日：2005-04-21

  Compounds of formula (I) and pharmaceutically acceptable salts thereof are disclosed: wherein A is optionally substituted phenyl, naphthyl, indolyl, quinolinyl, quinazolinyl, indazolyl, isoquinolinyl or benzofuranyl; b is 1, 2 or 3 and c is 1, 2 or 3, wherein b+c is 2, 3, 4 or 5; X is carbon, Y is CH, is a double bond and e is 0; or X is carbon, Y is CH 2 or oxygen, is a single bond and e is 1; or X is nitrogen, Y is CH 2 , is a single bond and e is 0; R1 is hydrogen, cyano, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxyC 1-6 alkyl, NHCOCH 3 or OCONR5R6, wherein R5 and R6 are independently hydrogen or C 1-6 alkyl; R2 is halogen, cyano or C 1-6 alkoxy; d is 0, 1, 2 or 3; R3 is hydrogen, C 1-6 alkyl, C 1-6 alkanoyl, fluoroC 1-6 alkanoyl, C 1-6 alkylsulfonyl, fluoroC 1-6 alkylsulfonyl, carbamoyl, C 1-6 alkylcarbamoyl or arylC 1-6 alkyl; and R4, together with the nitrogen atom to which it is attached, forms an optionally substituted 5 to 7 membered heterocyclic group fused to the benzene ring, provided that when a compound of formula (I) has the following structure: wherein A, b, c, R1, e, X, Y, R2 and d are as defined above and R3 is hydrogen, C 1-6 alkyl or arylC 1-6 alkyl, then (i) X is carbon, Y is CH and is a double bond; or (ii) b and c are both 1; or (iii) the carbon atom adjacent to the oxo-substituted carbon atom in the morpholinyl ring, marked “*”, is substituted. Methods of preparing the compounds and uses of the compounds in therapy, in particular for a CNS disorder such as depression or anxiety, are also disclosed.

  公开了式（I）的化合物及其药学上可接受的盐：其中，A是可选择取代的苯基，萘基，吲哚基，喹啉基，喹唑啉基，吲唑基，异喹啉基或苯并呋喃基；b为1、2或3，c为1、2或3，其中b+c为2、3、4或5；X为碳，Y为CH，为双键，e为0；或X为碳，Y为CH2或氧，为单键，e为1；或X为氮，Y为 ，为单键，e为0；R1为氢、氰、卤素、C1-6烷基、C1-6烷氧基、C1-6烷氧基C1-6烷基、NHCOCH3或OCONR5R6，其中R5和R6独立地为氢或C1-6烷基；R2为卤素、氰或C1-6烷氧基；d为0、1、2或3；R3为氢、C1-6烷基、C1-6酰基、氟代C1-6酰基、C1-6烷基磺酰基、氟代C1-6烷基磺酰基、氨基甲酰基、C1-6烷基氨基甲酰基或芳基C1-6烷基；而R4与其连接的氮原子形成一个可选择取代的5到7元杂环基，与苯环融合，但当式（I）的化合物具有以下结构时，则需满足以下条件：其中，A、b、c、R1、e、X、Y、R2和d如上所定义，而R3为氢、C1-6烷基或芳基C1-6烷基，那么（i）X为碳，Y为CH，为双键；或（ii）b和c均为1；或（iii）在吗啉环中与氧代取代碳原子相邻的碳原子，标记为“*”，被取代。还公开了制备这些化合物的方法以及这些化合物在治疗中的用途，特别是在治疗中枢神经系统疾病如抑郁症或焦虑症中的用途。
• 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）（ ）s，R3R4NCO（C2）s或R3R4NSO2（ ）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 ，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
• HETEROCYCLIC COMPOUNDS POSSESSING AFFINITY AT 5HT1-TYPE RECEPTORS AND USE THEREOF IN THERAPY
  申请人：GLAXO GROUP LIMITED

  公开号：EP1476444A1

  公开（公告）日：2004-11-17