1,4,7,8,9,10-Hexahydropyrido[3,4-f]quinoxaline-2,3-dione | 183545-79-1

• 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: 1,4,7,8,9,10-Hexahydropyrido[3,4-f]quinoxaline-2,3-dione
• CAS: 183545-79-1
• 化学式: C₁₁H₁₁N₃O₂
• 分子量: 217.227
• InChiKey: GJOVSWSOSXAOLA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  70.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,4,7,8,9,10-Hexahydropyrido[3,4-f]quinoxaline-2,3-dione 在 sodium hydroxide 、 硝酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 三氟乙酸 为溶剂， 生成 N-[2-(4-Hydroxy-phenyl)-ethyl]-4-[2-(6-nitro-2,3-dioxo-1,2,3,4,7,10-hexahydro-8H-pyrido[3,4-f]quinoxalin-9-yl)-acetylamino]-butyramide
  参考文献：
  名称：

  Synthesis of N-desmethyl PNQX: elaboration into an immunogenic conjugate and a radioiodinated ligand; radioimmunoassay for the AMPA/NMDA antagonist, PNQX

  摘要：

  A nine-step synthesis of N-desmethyl PNQX 5 and its subsequent elaboration into analogs, a porcine thyroglobulin immunogenic conjugate 8, and a radioiodinated analyte 10 are described. These compounds were used for the development of a specific radioimmunoassay for PNQX, a potent neuroprotective agent with mixed AMPA/NMDA glycine site antagonist activity. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00344-2
• 作为产物：
  描述：

  5-Bromo-7-nitro-1,2,3,4-tetrahydro-isoquinolin-8-ylamine 在 palladium on activated charcoal 盐酸 、 氢气 作用下， 生成 1,4,7,8,9,10-Hexahydropyrido[3,4-f]quinoxaline-2,3-dione
  参考文献：
  名称：

  Synthesis of N-desmethyl PNQX: elaboration into an immunogenic conjugate and a radioiodinated ligand; radioimmunoassay for the AMPA/NMDA antagonist, PNQX

  摘要：

  A nine-step synthesis of N-desmethyl PNQX 5 and its subsequent elaboration into analogs, a porcine thyroglobulin immunogenic conjugate 8, and a radioiodinated analyte 10 are described. These compounds were used for the development of a specific radioimmunoassay for PNQX, a potent neuroprotective agent with mixed AMPA/NMDA glycine site antagonist activity. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00344-2

文献信息

• Glutamate (ampa/kainate) receptor antagonists: N-substituted fused
  申请人：Warner-Lambert Company

  公开号：US06057313A1

  公开（公告）日：2000-05-02

  Novel N-substituted azacycloalkyl ring fused 2,3-quinoxalinediones are disclosed represented by the formula: ##STR1## or a pharmaceutically acceptable salt thereof, wherein R.sup.1 is hydrogen, alkyl or W-alkyl; X and Y are independently hydrogen, halogen, nitro, cyano, trifluoromethyl, SO.sub.2 CF.sub.3, SO.sub.2 R.sup.4, SO.sub.2 NR.sup.4 R.sup.5, alkyl, alkenyl, (CH.sub.2).sub.z CONR.sup.4 R.sup.5, (CH.sub.2).sub.z COOR.sup.4, or NHCOR.sup.4, wherein R.sup.4 and R.sup.5 are independently hydrogen, alkyl having 1 to 6 carbon atoms, cycloalkyl or W-alkyl, and z is an integer from 0 to 4; R.sup.2 is benzoyl, W, W-alkyl, COcycloalkyl, COalkyl-W, CONR.sup.3 alkyl, CONR.sup.3 -W, CONR.sup.3 alkyl-W, CSNR.sup.3 alkyl, CSNR.sup.3 alkyl-W, ##STR2## or a moiety derived from a common amino acid by removal of the --OH from the carboxyl group which is alpha to the amino, wherein --W is aryl, heteroaryl, or the heterocycles piperidinyl, piperazinyl, morpholinyl or pyrrolidinyl, wherein R.sup.3 is hydrogen, alkyl or W-alkyl; and m and n are independently 0, 1 or 2 provided that m+n is >1; provided that when R.sup.2 is benzoyl, ##STR3## or X is nitro, Y and R.sup.1 are H, m is 2 and n is 1; when R.sup.2 is ##STR4## X is nitro, Y and R.sup.1 are H and m is 2 and n is 1; or when R.sup.2 is ##STR5## X is bromo, Y and R.sup.1 are H, m is 1 and n is 2. The novel N-substituted azacycloalkyl ring fused 2,3-quinoxalinediones may be used, for example, as neuroprotective agents, for treatment of chronic neurodegenerative disorders, as anticonvulsants and in the treatment of schizophrenia, epilepsy, anxiety, pain and drug addiction.

  揭示了由以下公式表示的新型N-取代的环状氮杂环烷环融合的2,3-喹啉二酮，或其药学上可接受的盐：##STR1##其中，R1是氢、烷基或W-烷基；X和Y分别是氢、卤素、硝基、氰基、三氟甲基、SO2CF3、SO2R4、SO2NR4R5、烷基、烯基、(CH2)zCONR4R5、(CH2)zCOOR4或NHCOR4，其中，R4和R5分别是氢、具有1至6个碳原子的烷基、环烷基或W-烷基，z是从0到4的整数；R2是苯甲酰基、W、W-烷基、CO环烷基、CO烷基-W、CONR3烷基、CONR3-W、CONR3烷基-W、CSNR3烷基、CSNR3烷基-W、##STR2##或者是通过去除与氨基相邻的羧基上的-OH而来自常见氨基酸的基团，其中-W是芳基、杂芳基或杂环戊二烯基、哌啶基、哌嗪基、吗啉基或吡咯烷基，其中R3是氢、烷基或W-烷基；m和n独立地是0、1或2，但要求m+n>1；当R2是苯甲酰基、##STR3##或X是硝基、Y和R1是H、m是2而n是1时；当R2是##STR4##时，X是硝基、Y和R1是H，m是2而n是1；或当R2是##STR5##时，X是溴、Y和R1是H，m是1而n是2。这种新型的N-取代的环状氮杂环烷环融合的2,3-喹啉二酮可以用作神经保护剂，用于慢性神经退行性疾病的治疗，作为抗癫痫药物，并用于治疗精神分裂症、癫痫、焦虑、疼痛和药物成瘾。
• Glutamate (ampa/kainate) receptor antagonists: N-substituted fused azacycloalkylquinoxalinediones
  申请人：Warner-Lambert Company

  公开号：US06197771B1

  公开（公告）日：2001-03-06

  Novel N-substituted azacycloalkyl ring fused 2,3-quinoxalinediones represented by the formula: or a pharmaceutically acceptable salt thereof, are disclosed, wherein the formula variables R1, R2, X, Y, m and n are as defined herein. Also disclosed are methods of treatment using the same and intermediate compounds useful in the preparation thereof.

  本发明涉及一种由以下公式表示的N-取代的杂环烷基环融合2,3-喹喔啉二酮，或其药学上可接受的盐，其中公式中的变量R1、R2、X、Y、m和n的定义如本文所述。本发明还涉及使用该化合物的治疗方法以及在其制备中有用的中间体化合物。
• US6057313A
  申请人：——

  公开号：US6057313A

  公开（公告）日：2000-05-02
• US6197771B1
  申请人：——

  公开号：US6197771B1

  公开（公告）日：2001-03-06
• [EN] NOVEL GLUTAMATE (AMPA/KAINATE) RECEPTOR ANTAGONISTS: N-SUBSTITUTED FUSED AZACYCLOALKYLQUINOXALINEDIONES<br/>[FR] NOUVEAUX ANTAGONISTES DE RECEPTEURS DE GLUTAMATE (ACIDE AMP/KAINATE): AZACYCLOALKYLQUINOXALINEDIONES FUSIONNEES A SUBSTITUTION N
  申请人：WARNER-LAMBERT COMPANY

  公开号：WO1996028445A1

  公开（公告）日：1996-09-19

  (EN) Novel N-substituded azacycloalkyl ring fused 2,3-quinoxalinediones of formula (I), pharmaceutical compositions containing the same and the method of using the same, for the blockade of glutamate receptors, including either or both N-methyl-D-aspartate (NMDA) receptors and non-NMDA receptors such as the $g(a)-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor and the kainate receptor, are described. Method of preparing the N-substituted azacycloalkyl ring fused 2,3-quinoxalinediones are also described. Novel intermediates of the inventive quinoxalinediones are disclosed. The novel N-substituted azacycloalkyl ring fused 2,3-quinoxalinediones may be used, for example, as neuroprotective agents, for treatment of chronic neurodegenerative disorders, as anticonvulsants and in the treatment of schizophrenia, epilepsy, anxiety, pain and drug addiction. In formula (I) m and n are independently 0,1 or 2 provided that m + n is > 1. R1 is hydrogen, an alkyl or an alkylaryl; X and Y are independently hydrogen, halogen, nitro, cyano, trifluoromethyl, COOH, CONR4R5, SO2CF3, SO2R4, SONR4R5, alkyl, alkenyl, (CH2)zCONR4R5, (CH2)zCOOR4, or NHCOR4, wherein R4 and R5 are independently hydrogen, alkyl having 1 to 6 carton atoms, cycloalkyl or alkylaryl, and z is an integer from 0 to 4; R2 is alkylCOOR3, alkylamine, alkylquanidine, aryl, alkylaryl, COalkyl, COalkylaryl, CONR3alkyl, CONR3aryl, CONR3alkylaryl, CSNR3alkyl, CSNR3alkylaryl or a common amino acid moiety joined by an amide bond, wherein R3 is hydrogen, alkyl or alkylaryl.(FR) L'invention concerne des nouvelles 2,3-quinoxalinediones à substitution N fusionnées avec le cycle azacycloalkyle de la formule (I). Elle concerne également des compositions pharmaceutiques qui contiennent ces substances et leur procédé d'utilisation, pour le blocage des récepteurs de glutamate, y compris individuellement ou bien les deux à la fois les récepteurs de N-méthyl-D-aspartate (NMDA) et les récepteurs non NMDA comme le récepteur d'acide propionique $g(a)-amino-3-hydroxy-5-méthyle-4-isoxazole (Acide AMP) et le récepteur de kainate. On décrit également des procédés pour l'élaboration des 2,3-quinoxalinediones à substitution N fusionnées avec le cycle azacycloalkyle, ainsi que de nouveaux intermédiaires correspondant à ces quinoxalinediones. Les nouvelles substances en question peuvent être utilisées par exemple, comme agents neuroprotecteurs, pour le traitement des maladies neurodégénératives chroniques, comme anticonvulsifs et pour le traitement de la schizophrénie, de l'épilepsie, de l'anxiété, de la douleur et de la toxicomanie. Dans ladite formule, m et n valent indépendamment 0,1, ou bien 2 à condition que m + n > 1. R1 désigne hydrogène, un alkyle ou un alkylaryle; X et Y représentent indépendamment hydrogène, halogène, nitro, cyano, trifluorométhyle, COOH, CONR4R5, SO2CF3, SO2R4, SONR4R5, alkyle, alcényle, (CH2)zCONR4R5, (CH2zCOOR4, ou NHCOR4, R4 et R5 désignant indépendamment hydrogène, alkyle ayant de 1 à 6 atomes de carbone, cycloalkyle ou alkylaryle, et z est un nombre entier compris entre 0 et 4; R2 représente alkyleCOOR3, alkylamine, alkylquanidine, aryle, alkylaryle, COalkyle, COalkylaryle, CONR3alkyle, CONR3aryle, CONR3alkylaryle, CSNR3alkyle, CSNR3alkylaryle ou une fraction d'acide aminé commune reliée par une liaison amide, R3 désignant hydrogène, alkyle ou alkylaryle.