methyl [(4-hydroxy-2-nitrophenyl)oxy]acetate | 583031-18-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl [(4-hydroxy-2-nitrophenyl)oxy]acetate
• 英文别名: (4-hydroxy-2-nitrophenoxy)acetic acid methyl ester；4-(Methoxycarbonylmethoxy)-3-nitrophenol；methyl 2-(4-hydroxy-2-nitrophenoxy)acetate
• CAS: 583031-18-9
• 化学式: C₉H₉NO₆
• 分子量: 227.174
• InChiKey: QSWRASDYZNMURQ-UHFFFAOYSA-N

物化性质

• 沸点：
  401.0±35.0 °C(Predicted)
• 密度：
  1.418±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl [(4-hydroxy-2-nitrophenyl)oxy]acetate 在 palladium on activated charcoal 盐酸 、 偶氮二甲酸二异丙酯 、 氢气 、 三苯基膦 作用下， 以 四氢呋喃 、 乙醚 、 异丙醇 为溶剂， 20.0~50.0 ℃ 、300.0 kPa 条件下， 反应 54.0h， 生成 6-(piperidin-4-yloxy)-4H-benzo[1,4]oxazin-3-one hydrochloride
  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：

  4-羟基-3-硝基苯基苯甲酸酯 在 sodium methylate 、 potassium carbonate 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 19.0h， 生成 methyl [(4-hydroxy-2-nitrophenyl)oxy]acetate
  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

• Novel 5-HT1A/1B/1D receptors antagonists with potent 5-HT reuptake inhibitory activity
  作者：Halina T. Serafinowska、Frank E. Blaney、Peter J. Lovell、Giancarlo G. Merlo、Claire M. Scott、Paul W. Smith、Kathryn R. Starr、Jeannette M. Watson

  DOI：10.1016/j.bmcl.2008.08.110

  日期：2008.10

  5-HT(1A/1B/1D) receptors coupled with potent 5-HT reuptake inhibitory activity have been discovered. This is the first report describing docking of the lead compound 6-2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}-2H-1,4-benzoxazin-3(4H)-one 1, into a model of the 5-HT transporter and the 5-HT(1A) receptor model.

  新型2-甲基-5-喹啉基-1-哌嗪基烷基-3,4-二氢-2H-1,4-苯并恶嗪-3-酮对5-HT（1A / 1B / 1D）受体表现出高亲和力，并与强效5偶联已经发现了-HT再摄取抑制活性。这是描述铅化合物6- 2- [4-（2-（5-甲基-5-喹啉基）-1-哌嗪基]乙基} -2H-1,4-苯并恶嗪-3（4H）-对接的第一份报告如图1所示，将模型转换成5-HT转运蛋白和5-HT（1A）受体模型。
• [EN] BENZOXAZINONE DERIVATIVES, PREPARATION THEREOF AND USES IN THE TREATMENT OF CNS AND OTHER DISORDERS<br/>[FR] DERIVES DE BENZOXAZINONE, PREPARATION DE CEUX-CI ET UTILISATIONS DE CEUX-CI DANS LE TRAITEMENT DE TROUBLES DU SNC ET D'AUTRES TROUBLES
  申请人：GLAXO GROUP LTD

  公开号：WO2004046124A1

  公开（公告）日：2004-06-03

  Compounds of formula (I) and pharmaceutically acceptable salts thereof are disclosed:wherein A, R1, R2, R3, p, q, A and X are as defined in the specification. Preparation of the compounds and uses in the treatment of CNS and other disorders, including depression and anxiety, are also disclosed.

  公开了化合物的公式(I)及其药用盐：其中A、R1、R2、R3、p、q、A和X的定义如规范中所述。还公开了化合物的制备方法以及在治疗中枢神经系统和其他疾病，包括抑郁症和焦虑症中的用途。
• [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。
• Heterocyclymethylpiperidines and -piperazines possessing affinity at 5ht-1 type receptors
  申请人：Ward E. Simon

  公开号：US20050153974A1

  公开（公告）日：2005-07-14

  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; X is carbon, Y is CH and is a double bond; or X is CH, Y is CH 2 or oxygen and is a single bond; or X is nitrogen, Y is CH 2 and is a single bond; R1 is halogen, cyano, or C 1-6 alkoxy; a is 0, 1, 2 or 3; b is 0 or 1; R2 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 R3, 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. 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.

  公开了化学式（I）的化合物及其药用可接受的盐：其中：A是可选取代的苯基、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；X是碳，Y是CH且是双键；或X是CH，Y是CH2或氧且是单键；或X是氮，Y是CH2且是单键；R1是卤素、氰基或C1-6烷氧基；a为0、1、2或3；b为0或1；R2是氢、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；R3与其连接的氮原子一起形成一个可选取代的5到7元杂环基固定在苯环上。还公开了制备该化合物的方法以及该化合物在治疗中的用途，特别是用于中枢神经系统紊乱如抑郁症或焦虑症。