6-(4-(2-(2-Methylquinolin-5-yloxy)ethyl)piperazin-1-ylmethyl)-4H-benzo[1,4]oxazin-3-one | 420785-77-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 6-(4-(2-(2-Methylquinolin-5-yloxy)ethyl)piperazin-1-ylmethyl)-4H-benzo[1,4]oxazin-3-one
• 英文别名: 6-[[4-[2-(2-methylquinolin-5-yl)oxyethyl]piperazin-1-yl]methyl]-4H-1,4-benzoxazin-3-one
• CAS: 420785-77-9
• 化学式: C₂₅H₂₈N₄O₃
• 分子量: 432.522
• InChiKey: JXYPPXBLBAOPFD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  66.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-(4-(2-(2-Methylquinolin-5-yloxy)ethyl)piperazin-1-ylmethyl)-4H-benzo[1,4]oxazin-3-one 、 Lithium aluminium hydride 在 氩 、 Rochelle's salt 、 乙酸乙酯 、 水 、 Brine 、 magnesium sulfate 、 SiO2 、 0.880 、 ammonia methanol 、 二氯甲烷 作用下， 以 四氢呋喃 为溶剂， 反应 19.0h， 以gave the title compound (0.073 g, 54%) as a yellow foam的产率得到6-{4-[2-(2-Methylquinolin-5-yloxy)ethyl]piperazin-1-ylmethyl}-3,4-dihydro-2H-benzo[1,4]oxazine
  参考文献：
  名称：

  Heterocyclic compounds possessing affinity at 5HT1 -type receptors and use thereof in therapy

  摘要：

  本文披露了化合物(I)的公式及其药学上可接受的盐：其中A为可选取的取代苯基、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CH2，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C1-6酰基、C1-6烷基磺酰基、氟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的取代的5到7成员杂环基团融合到苯环上，但当化合物(I)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，则(i)X为碳，Y为CH，为双键；或(ii)b和c都为1；或(iii)在哌嗪环中氧代取代的碳原子相邻的碳原子，标记为“★”，被取代。本文还披露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，特别是用于中枢神经系统障碍，如抑郁症或焦虑症。

  公开号：

  US07244726B2
• 作为产物：
  描述：

  tert-butyl 4-[2-(2-methylquinolin-5-yloxy)ethyl]piperazine-1-carboxylate 在 盐酸 、 三乙酰氧基硼氢化钠 作用下， 以 乙醚 、 乙醇 、 1,2-二氯乙烷 为溶剂， 生成 6-(4-(2-(2-Methylquinolin-5-yloxy)ethyl)piperazin-1-ylmethyl)-4H-benzo[1,4]oxazin-3-one
  参考文献：
  名称：

  Discovery of the First Potent, Selective 5-Hydroxytryptamine_1D Receptor Antagonist

  摘要：

  A series of 5-(piperidinylethyloxy)quinoline 5-hydroxytryptamine(1D) (5-HT1D) receptor antagonists have been discovered from elaboration of the series of dual 5-hydroxy-tryptamine(1) -selective serotonin reuptake inhibitors (5HT(1)-SSRIs) reported previously. This is the first report of highly potent, selective antagonists for the 5-HT1D receptor, which represents an extremely useful set of pharmacological tools for further understanding the roles of the 5-HT1 receptor subtypes.

  DOI：

  10.1021/jm049039v

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CH2，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CH2，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。
• Studies on a series of potent, orally bioavailable, 5-HT1 receptor ligands
  作者：Simon E. Ward、Christopher N. Johnson、Peter J. Lovell、Claire M. Scott、Paul W. Smith、Geoffrey Stemp、Kevin M. Thewlis、Antonio K. Vong、Jeannette M. Watson

  DOI：10.1016/j.bmcl.2007.06.078

  日期：2007.9

  A series of 5-(piperidinylethyloxy)quinoline 5-HT1 receptor ligands have been studied by elaboration of the series of dual 5-HT1-SSRIs reported previously. These new compounds display a different pharmacological profile with potent affinity across the 5-HT1A, 5-HT1B and 5-HT1D receptors and selectivity against the serotonin transporter. Furthermore, they have improved pharmacokinetic profiles and CNS penetration. (c) 2007 Elsevier Ltd. All rights reserved.
• 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
• US7244726B2
  申请人：——

  公开号：US7244726B2

  公开（公告）日：2007-07-17