tert-butyl 4-[(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)oxy]piperidine-1-carboxylate | 583031-07-6

• 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: tert-butyl 4-[(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)oxy]piperidine-1-carboxylate
• 英文别名: tert-Butyl 4-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yloxy)piperidine-1-carboxylate；tert-butyl 4-[(2-oxo-3,4-dihydro-1H-quinolin-7-yl)oxy]piperidine-1-carboxylate
• CAS: 583031-07-6
• 化学式: C₁₉H₂₆N₂O₄
• 分子量: 346.426
• InChiKey: UHWSFSBSYBABFC-UHFFFAOYSA-N

物化性质

• 沸点：
  517.4±50.0 °C(Predicted)
• 密度：
  1.180±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-[(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)oxy]piperidine-1-carboxylate 在 盐酸 作用下， 以 乙醚 为溶剂， 生成 7-(piperidin-4-yloxy)-3,4-dihydroquinolin-2(1H)-one
  参考文献：
  名称：

  强大的二氢喹啉酮多巴胺D 2部分激动剂/血清素再摄取抑制剂，用于治疗精神分裂症

  摘要：

  当与某些胺结合时，发现二氢喹啉酮部分是有效的5-羟色胺再摄取抑制剂药效基团。该片段与选择的D 2配体偶联以制备一系列具有有吸引力的体外作用的双作用化合物，如多巴胺D 2部分激动剂和5-羟色胺再摄取抑制剂。结构活性研究表明，该接头在促进D 2亲和力，功能和SRI活性中起关键作用。

  DOI：

  10.1016/j.bmcl.2010.02.105
• 作为产物：
  描述：

  3,4-二氢-7-羟基-2(1H)-喹啉酮 、 t-butyl 4-(2-nitrophenylsulfonyloxy)piperidine-1-carboxylate 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 tert-butyl 4-[(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)oxy]piperidine-1-carboxylate
  参考文献：
  名称：

  强大的二氢喹啉酮多巴胺D 2部分激动剂/血清素再摄取抑制剂，用于治疗精神分裂症

  摘要：

  当与某些胺结合时，发现二氢喹啉酮部分是有效的5-羟色胺再摄取抑制剂药效基团。该片段与选择的D 2配体偶联以制备一系列具有有吸引力的体外作用的双作用化合物，如多巴胺D 2部分激动剂和5-羟色胺再摄取抑制剂。结构活性研究表明，该接头在促进D 2亲和力，功能和SRI活性中起关键作用。

  DOI：

  10.1016/j.bmcl.2010.02.105

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 ，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 ，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。
• ANTIDEPRESSANT HETEROARYL DERIVATIVES OF HETEROCYCLE-FUSED BENZODIOXANS
  申请人：Failli Amedeo A.

  公开号：US20090042874A1

  公开（公告）日：2009-02-12

  The invention provides compounds of the Formula: that are useful for the treatment of depression (including but not limited to major depressive disorder, childhood depression and dysthymia), anxiety, panic disorder, post-traumatic stress disorder, premenstrual dysphoric disorder (also known as pre-menstrual syndrome), attention deficit disorder (with and without hyperactivity), obsessive compulsive disorder, social anxiety disorder, generalized anxiety disorder, obesity, eating disorders such as anorexia nervosa, bulimia nervosa, vasomotor flushing, cocaine and alcohol addiction, sexual dysfunction and related illnesses.

  该发明提供了下列式的化合物，该化合物对于治疗抑郁症（包括但不限于重度抑郁障碍、儿童抑郁症和心境不良）、焦虑症、恐慌症、创伤后应激障碍、经前期失调症（也称为经前综合征）、注意力缺陷多动障碍（有和没有过度活跃）、强迫症、社交焦虑障碍、广泛性焦虑障碍、肥胖症、饮食紊乱如厌食症、贪食症、潮红、可卡因和酒精成瘾、性功能障碍及相关疾病具有有益作用。
• WO2008/150848
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] ANTIDEPRESSANT HETEROARYL DERIVATIVES OF HETEROCYCLE-FUSED BENZODIOXANS<br/>[FR] DÉRIVÉS D'HÉTÉRO-ARYLE ANTIDÉPRESSEURS DE BENZODIOXANES CONDENSÉS AVEC UN HÉTÉROCYCLE
  申请人：WYETH CORP

  公开号：WO2008150848A1

  公开（公告）日：2008-12-11

  [EN] The invention provides compounds of the Formula: (I) that are useful for the treatment of depression (including but not limited to major depressive disorder, childhood depression and dysthymia), anxiety, panic disorder, post-traumatic stress disorder, premenstrual dysphoric disorder (also known as pre- menstrual syndrome), attention deficit disorder (with and without hyperactivity), obsessive compulsive disorder, social anxiety disorder, generalized anxiety disorder, obesity, eating disorders such as anorexia nervosa, bulimia nervosa, vasomotor flushing, cocaine and alcohol addiction, sexual dysfunction and related illnesses. The compounds are able to block the recptake of serotonin and are modulators at brain 5HT1A serotonin receptors.
  [FR] La présente invention concerne des composés de formule : qui sont utiles pour le traitement de la dépression (comprenant, de manière non restrictive, les troubles dépressifs majeurs, la dépression juvénile et la dysthymie), l'anxiété, les troubles paniques, les troubles liés au stress post-traumatique, les troubles dysphoriques prémenstruels (connus également sous le nom de syndrome prémenstruel), les troubles avec déficit d'attention (avec et sans hyperactivité), les troubles obsessionnels compulsifs, les troubles anxieux sociaux, les troubles anxieux généralisés, l'obésité, les troubles alimentaires tels que l'anorexie mentale, la boulimie nerveuse, les bouffées vasomotrices, la dépendance à la cocaïne et à l'alcool, les dysfonctionnements sexuels et les maladies apparentées. Les composés sont capables de bloquer la recapture de la sérotonine et sont des modulateurs au niveau des récepteurs cérébraux de la sérotonine 5HT1A.