6-ethoxy-4-oxo-1,4-dihydro[1,5]naphthyridine-3-carboxylic acid ethyl ester | 92808-33-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 6-ethoxy-4-oxo-1,4-dihydro[1,5]naphthyridine-3-carboxylic acid ethyl ester
• 英文别名: 6-ethoxy-4-oxo-1,4-dihydro-1,5-naphthyridine-3-carboxylic acid ethyl ester；ethyl 6-ethoxy-4-oxo-1,4-dihydro-1,5-naphthyridine-3-carboxylate；ethyl 6-ethoxy-4-oxo-1H-1,5-naphthyridine-3-carboxylate
• CAS: 92808-33-8；162220-91-9
• 化学式: C₁₃H₁₄N₂O₄
• 分子量: 262.265
• InChiKey: CBWAMIDNURTBLL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  77.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-ethoxy-4-oxo-1,4-dihydro[1,5]naphthyridine-3-carboxylic acid ethyl ester 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 6-乙氧基-4-氧代-1,4-二氢-1,5-萘啶-3-羧酸
  参考文献：
  名称：

  Substituted 4-oxo-napthyridine-3-carboxamides: GABA brain receptor

  摘要：

  本发明涵盖了以下结构的化合物：##STR1## 或其药学上可接受的无毒盐，其中：x为氢、卤素、（未）取代的烷基、（未）取代的烷氧基或氨基；Y为（未）取代的烷基、芳基或杂环芳基，这些化合物是高度选择性的GABAa脑受体的激动剂、拮抗剂或逆拮抗剂，或者是GABAa脑受体激动剂、拮抗剂或逆拮抗剂的前药。这些化合物在焦虑、唐氏综合征、睡眠、认知和癫痫障碍的诊断和治疗以及苯二氮卓类药物过量和警觉度增强方面很有用。

  公开号：

  US06143760A1
• 作为产物：
  描述：

  diethyl 2-(6-ethoxy-pyridin-3-ylaminomethylene)malonate 在 乙醚 、 hexanes 作用下， 以 二苯醚 为溶剂， 反应 0.5h， 以to gave 2.98 g of ethyl 6-ethoxy-4-oxo-1,4-dihydro-1,5-naphthyridine-3-carboxylate as a tan solid的产率得到6-ethoxy-4-oxo-1,4-dihydro[1,5]naphthyridine-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  Substituted 4-oxo-napthyridine-3-carboxamides: GABA brain receptor ligands

  摘要：

  本发明涵盖了Formula1的结构或其药学上可接受的非毒性盐，其中：X为氢、卤素、(未)取代烷基、(未)取代烷氧基或氨基；Y为(未)取代烷基、芳基或杂环芳基，这些化合物是高度选择性的GABAa脑受体的激动剂、拮抗剂或反向激动剂，或者是GABAa脑受体激动剂、拮抗剂或反向激动剂的前药。这些化合物在焦虑、唐氏综合症、睡眠、认知和癫痫障碍、苯二氮平类药物过量和警觉性增强的诊断和治疗中有用。

  公开号：

  US20020156280A1

文献信息

• Condensed 4-aminopyridines with antirheumatic activity
  申请人：Knoll Aktiengesellschaft

  公开号：US05780482A1

  公开（公告）日：1998-07-14

  Compounds of formula I ##STR1## and pharmaceutically acceptable salts thereof in which one of A or B represents N and the other represents N or C--R.sub.3 ; R.sub.1 represents hydrogen, halo, alkyl, hydroxy, carboxyalkenyl, alkoxycarbonylalkenyl, hydroxyalkyl, carboxyalkyl, alkoxycarbonylalkyl, alkoxy, halogenated alkyl, carboxy, alkoxycarbonyl, alkanoylamino or carbamoylalkenyl; R.sub.2 represents hydrogen, alkyl, halo, alkoxy, hydroxy, alkanoyloxy, or phenoxy; R.sub.3 represents hydrogen or alkyl; R.sub.4 represents hydrogen, halo, alkoxycarbonyl, cyano, benzyloxycarbonyl, alkanoyl, benzoyl, alkyl, carboxy, alkylthio or carbamoyl; R.sub.5 represents hydrogen or alkyl; R.sub.9 represents hydrogen or alkyl; R.sub.10 represents phenyl, pyridyl or pyrimidinyl substituted by OR.sub.6 and optionally further substituted wherein R.sub.6 represents hydrogen, alkyl, alkoxycarbonyl or carbamoyl, alicyclic hydrocarbon, phenyl, cycloalkylalkyl, arylalkyl or pyridyl; or when R.sub.10 represents phenyl, OR.sub.6 represents a monosaccharide group or a disaccharide group; which are antirheumatic agents. Compositions containing these compounds and processes to prepare them are also disclosed.

  化学式I的化合物及其药学上可接受的盐，其中A或B中的一个代表N，另一个代表N或C--R.sub.3；R.sub.1代表氢、卤素、烷基、羟基、羧烯基、烷氧羰基烯基、羟基烷基、羧基烷基、烷氧羰基烷基、烷氧基、卤代烷基、羧基、烷氧羰基、烷酰胺基或氨基烯基；R.sub.2代表氢、烷基、卤素、烷氧基、羟基、烷酰氧基或苯氧基；R.sub.3代表氢或烷基；R.sub.4代表氢、卤素、烷氧羰基、氰基、苄氧羰基、烷酰基、苯甲酰基、烷基、羧基、烷硫基或氨基甲酰；R.sub.5代表氢或烷基；R.sub.9代表氢或烷基；R.sub.10代表苯基、吡啶基或嘧啶基，被OR.sub.6取代，并且可选择进一步取代，其中R.sub.6代表氢、烷基、烷氧羰基或氨基，脂环烃、苯基、环烷基烷基、芳基烷基或吡啶基；或当R.sub.10代表苯基时，OR.sub.6代表单糖基或双糖基；这些化合物是抗风湿药物。揭示了含有这些化合物的组合物和制备它们的方法。
• [EN] PROCESS FOR THE PREPARATION AND PURIFICATION OF 1,5-NAPHTHYRIDINE-3-CARBOXYAMIDES<br/>[FR] PROCEDE DE PREPARATION ET DE PURIFICATION DE 1,5-NAPHTYRIDINE-3-CARBOXYAMIDES
  申请人：PFIZER PROD INC

  公开号：WO2004106336A1

  公开（公告）日：2004-12-09

  A new route for the preparation and purification of substituted 1,5-naphthyridine-3­carboxyamides, useful in the diagnosis and treatment of anxiety, Downs Syndrome, sleep, cognitive and seizure disorders, and overdose with benzodiazepine drugs and for enhancement of alertness, is provided. These compounds may be readily prepared by treating the corresponding 1,5-naphthyridine-3-carboxylic acids with a primary amine and a 1,1-carbonyldiimidazole. Purification is achieved by converting the substituted 1,5­naphthyridine-3-carboxyamides to a salt with a strong base such as potassium t-butoxide, recrystallizing and acidifying to regenerate the pure carboxyamide.

  提供了一种新的制备和纯化取代的1,5-萘啶-3-羧酰胺的方法，这些化合物在焦虑、唐氏综合症、睡眠、认知和癫痫障碍以及苯二氮平类药物过量和警觉性增强方面有用。这些化合物可以通过用一级胺和1,1-羰基二咪唑处理相应的1,5-萘啶-3-羧酸制备而成。通过将取代的1,5-萘啶-3-羧酰胺转化为强碱盐（如叔丁基钾），再通过重结晶和酸化来得到纯的羧酰胺。
• Process for the preparation of 1,5-naphthyridine-3-carboxyamides by direct ester amidation
  申请人：Karrick L. Gregory

  公开号：US20050038065A1

  公开（公告）日：2005-02-17

  A new route for the preparation of substituted 1,5-naphthyridine-3-carboxyamides, useful in the diagnosis and treatment of anxiety, Downs Syndrome, sleep, cognitive and seizure disorders, and overdose with benzodiazepine drugs and for enhancement of alertness, is provided. These compounds may be readily prepared by heating the corresponding 1,5-naphthyridine-3-carboxylic acid ester with a primary amine in a polar solvent such as dimethylformamide or dimethylsulfoxide.

  提供了一种制备取代的1,5-萘啶-3-羧酰胺的新途径，该化合物在焦虑、唐氏综合症、睡眠、认知和癫痫障碍、苯二氮平类药物过量和提高警觉性方面有用。这些化合物可以通过在极性溶剂如二甲基甲酰胺或二甲基亚砜中加热相应的1,5-萘啶-3-羧酸酯和一级胺来轻松制备。
• Substituted 4-OXO-napthyridine-3-carboxamides; GABA brain receptor ligands
  申请人：Neurogen Corporation

  公开号：US06399604B1

  公开（公告）日：2002-06-04

  The present invention encompasses structures of the Formula or the pharmaceutically acceptable non-toxic salts thereof wherein: X is hydrogen, halogen, (un)substituted alkyl, (un)substituted alkoxy or amino; and Y is (un)substituted alkyl, aryl, or heteroaryl, which compounds are highly selective agonists, antagonists or inverse agonists for GABAa brain receptors or prodrugs of agonists, antagonists or inverse agonists for GABAa brain receptors. These compounds are useful in the diagnosis and treatment of anxiety, Down Syndrome, sleep, cognitive and seizure disorders, and overdose with benzodiazepine drugs and for enhancement of alertness.

  本发明涉及公式的结构或其药学上可接受的非毒性盐，其中：X为氢、卤素、(未)取代烷基、(未)取代烷氧基或氨基；而Y为(未)取代烷基、芳基或杂环芳基。这些化合物是高度选择性的GABAa脑受体激动剂、拮抗剂或反向激动剂，或是GABAa脑受体激动剂、拮抗剂或反向激动剂的前药。这些化合物在焦虑症、唐氏综合征、睡眠、认知和癫痫障碍的诊断和治疗以及苯二氮䓬类药物过量和提高警觉性方面是有用的。
• Synthesis and Purification of 6-Ethoxy-4-oxo-1,4-dihydro-[1,5]naphthyridine-3-carboxylic Acid Benzylamide
  作者：Justin Beaudin、Dennis E. Bourassa、Paul Bowles、Michael J. Castaldi、Ronald Clay、Michel A. Couturier、Gregory Karrick、Teresa W. Makowski、Ruth E. McDermott、Clifford N. Meltz、Morgan Meltz、James E. Phillips、John A. Ragan、David H. Brown Ripin、Robert A. Singer、John L. Tucker、Lulin Wei

  DOI：10.1021/op0341061

  日期：2003.11.1

  The synthesis of 6-ethoxy-4-oxo-1,4-dihydro-[1,5]naphthyridine-3-carboxylic acid benzylamide (1) on multikilogram scale is described. The major challenge for the synthesis of this quinolone GABA partial agonist was in the isolation of product of acceptable purity for clinical studies due to the insolubility of this compound. Also described are efforts to circumvent a high-temperature cyclization required for the synthesis of the quinolone ring system.