tert-butyl 4-((3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)methyl)piperazine-1-carboxylate | 420786-62-5

• 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: tert-butyl 4-((3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)methyl)piperazine-1-carboxylate
• 英文别名: 6-(4-(tert-Butyloxycarbonyl)piperazin-1-ylmethyl)-4H-benzo[1,4]oxazin-3-one；tert-butyl 4-[(3-oxo-4H-1,4-benzoxazin-6-yl)methyl]piperazine-1-carboxylate
• CAS: 420786-62-5
• 化学式: C₁₈H₂₅N₃O₄
• 分子量: 347.414
• InChiKey: XEVAMLYNDLGIOD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  71.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-((3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)methyl)piperazine-1-carboxylate 在 盐酸 作用下， 以 乙醚 、 异丙醇 为溶剂， 反应 18.0h， 生成
  参考文献：
  名称：

  3,4-Dihydro-2H-benzoxazinones are 5-HT1A receptor antagonists with potent 5-HT reuptake inhibitory activity

  摘要：

  Starting from a high throughput screening hit, a series of 3,4-dihydro-2H-benzoxazinones has been identified with both high affinity for the 5-HT1A receptor and potent 5-HT reuptake inhibitory activity. The 5-(2-methyl)quinolinyloxy derivative combined high 5-HT1A/1B/1D receptor affinities with low intrinsic activity and potent inhibition of the 5-HT reuptake site (pK(i) 8.2). This compound also had good oral bioavailability and brain penetration in the rat. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.11.030
• 作为产物：
  描述：

  3-氧代-3,4-二氯-2H-苯并[1,4]恶嗪-6-甲醛 、 N-Boc-哌嗪 在 三乙酰氧基硼氢化钠 作用下， 反应 18.0h， 生成 tert-butyl 4-((3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)methyl)piperazine-1-carboxylate
  参考文献：
  名称：

  3,4-Dihydro-2H-benzoxazinones are 5-HT1A receptor antagonists with potent 5-HT reuptake inhibitory activity

  摘要：

  Starting from a high throughput screening hit, a series of 3,4-dihydro-2H-benzoxazinones has been identified with both high affinity for the 5-HT1A receptor and potent 5-HT reuptake inhibitory activity. The 5-(2-methyl)quinolinyloxy derivative combined high 5-HT1A/1B/1D receptor affinities with low intrinsic activity and potent inhibition of the 5-HT reuptake site (pK(i) 8.2). This compound also had good oral bioavailability and brain penetration in the rat. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.11.030

文献信息

• 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。
• Heterocyclic compounds possessing affinity at 5HT1 -type receptors and use thereof in therapy
  申请人：Glaxo Group Limited

  公开号：US07244726B2

  公开（公告）日：2007-07-17

  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 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.

  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。
• POLY (ADP-RIBOSE) POLYMERASE (PARP) INHIBITORS
  申请人：Brown Jason W.

  公开号：US20120094992A1

  公开（公告）日：2012-04-19

  Compounds of the following formula are provided for use in inhibiting Poly (ADP-ribose) Polymerase (PARP): wherein the variables are defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such compounds, methods and intermediates useful for making the compounds, and methods of using the compounds.

  以下式子的化合物被提供用于抑制Poly (ADP-ribose) Polymerase (PARP)的作用： 其中变量在此定义。还提供了制备该化合物的药物组合物、工具箱和制造品、中间体的方法以及使用该化合物的方法。
• Poly (ADP-ribose) Polymerase (PARP) Inhibitors
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP2415767A1

  公开（公告）日：2012-02-08

  The invention provides compounds of the general formula (1): wherein the variables are as defined herein. The compounds have use in inhibiting poly (ADP-ribose) Polymerase (PARP). The invention also provides pharmaceutical compositions containing the compounds and their use as medicaments.

  本发明提供通式（1）的化合物： 其中的变量如本文所定义。这些化合物可用于抑制聚（ADP-核糖）聚合酶（PARP）。本发明还提供了含有这些化合物的药物组合物及其作为药物的用途。
• [EN] POLY (ADP-RIBOSE) POLYMERASE (PARP) INHIBITORS<br/>[FR] INHIBITEURS DE LA POLY(ADP-RIBOSE)POLYMÉRASE (PARP)
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2010111626A3

  公开（公告）日：2010-11-18