8-bromo-5-(phthalimidomethyl)-5,6-dihydro-1H-pyrrolo<1,2,3-de>quinoxaline-2,3-dione | 150533-69-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 8-bromo-5-(phthalimidomethyl)-5,6-dihydro-1H-pyrrolo<1,2,3-de>quinoxaline-2,3-dione
• 英文别名: 8-bromo-5-phthalimidomethyl-5,6-dihydro-1H-pyrrolo[1,2,3-de]quinoxaline-2,3-dione；6-bromo-2-[(1,3-dioxoisoindol-2-yl)methyl]-1,9-diazatricyclo[6.3.1.04,12]dodeca-4(12),5,7-triene-10,11-dione
• CAS: 150533-69-0
• 化学式: C₁₉H₁₂BrN₃O₄
• 分子量: 426.226
• InChiKey: QXHSCZCEIJNVQC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  86.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-bromo-5-(phthalimidomethyl)-5,6-dihydro-1H-pyrrolo<1,2,3-de>quinoxaline-2,3-dione 在 盐酸 、 溶剂黄146 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 7.5h， 生成 8-bromo-5-<(N'-phenylureido)methyl>-5,6-dihydro-1H-pyrrolo<1,2,3-de>quinoxaline-2,3-dione
  参考文献：
  名称：

  Tricyclic Quinoxalinediones: 5,6-Dihydro-1H-pyrrolo[1,2,3-de]quinoxaline-2,3-diones and 6,7-Dihydro-1H,5H-pyrido[1,2,3-de]quinoxaline-2,3-diones as Potent Antagonists for the Glycine Binding Site of the NMDA Receptor

  摘要：

  A series of tricyclic quinoxalinediones, 5,6-dihydro-1H-pyrrolo[1,2,3-de]quinoxaline-2,3-diones and 6,7-dihydro-1H,5H-pyrido[1,2,3-de]quinoxaline-2,3-diones, were synthesized and was evaluated for their affinity for the glycine binding site of the NMDA receptor using a [H-3]- 5,7-dichlorokynurenic acid binding assay. The six-membered ring-fused tricyclic quinoxalinedione 18g (K-i = 9.9 nM) displayed high affinity for the glycine site. The anilide derivative 20g (K-i = 2.6 nM) was 4-fold more potent than 18g and as potent as L-689,560, one of the most potent glycine antagonists so far prepared. Although the carboxylic acid derivative of the corresponding five-membered ring-fused tricyclic quinoxalinedione 18e (K-i = 7.3 nM) had affinity comparable to that of 18g, the anilide derivative 20e largely decreased in the affinity in contrast to 20g. Enantiomers 23g, 24g, 25g, and 26g were prepared and tested. Only the S enantiomer 25g (K-i = 0.96 nM) retained the affinity among the anilide derivatives, whereas both enantiomers 23g (K-i = 2.3 nM) and 24g (K-i = 9.6 nM) were active among the carboxylic acid derivatives. The origin of the high affinity of carboxylic acid derivatives such as 18e and 18g would be a charge-charge interaction between the anionic carboxylate residues of the compounds and the cationic proton-donor site in the receptor.

  DOI：

  10.1021/jm00049a015
• 作为产物：
  描述：

  2,3-二氢-1H-吲哚-2-羧酸甲酯 在 lithium aluminium tetrahydride 、 titanium(III) chloride 、 硝酸异丙酯 、 硫酸 、 氨 、 溴 、 铁粉 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 31.25h， 生成 8-bromo-5-(phthalimidomethyl)-5,6-dihydro-1H-pyrrolo<1,2,3-de>quinoxaline-2,3-dione
  参考文献：
  名称：

  Tricyclic Quinoxalinediones: 5,6-Dihydro-1H-pyrrolo[1,2,3-de]quinoxaline-2,3-diones and 6,7-Dihydro-1H,5H-pyrido[1,2,3-de]quinoxaline-2,3-diones as Potent Antagonists for the Glycine Binding Site of the NMDA Receptor

  摘要：

  A series of tricyclic quinoxalinediones, 5,6-dihydro-1H-pyrrolo[1,2,3-de]quinoxaline-2,3-diones and 6,7-dihydro-1H,5H-pyrido[1,2,3-de]quinoxaline-2,3-diones, were synthesized and was evaluated for their affinity for the glycine binding site of the NMDA receptor using a [H-3]- 5,7-dichlorokynurenic acid binding assay. The six-membered ring-fused tricyclic quinoxalinedione 18g (K-i = 9.9 nM) displayed high affinity for the glycine site. The anilide derivative 20g (K-i = 2.6 nM) was 4-fold more potent than 18g and as potent as L-689,560, one of the most potent glycine antagonists so far prepared. Although the carboxylic acid derivative of the corresponding five-membered ring-fused tricyclic quinoxalinedione 18e (K-i = 7.3 nM) had affinity comparable to that of 18g, the anilide derivative 20e largely decreased in the affinity in contrast to 20g. Enantiomers 23g, 24g, 25g, and 26g were prepared and tested. Only the S enantiomer 25g (K-i = 0.96 nM) retained the affinity among the anilide derivatives, whereas both enantiomers 23g (K-i = 2.3 nM) and 24g (K-i = 9.6 nM) were active among the carboxylic acid derivatives. The origin of the high affinity of carboxylic acid derivatives such as 18e and 18g would be a charge-charge interaction between the anionic carboxylate residues of the compounds and the cationic proton-donor site in the receptor.

  DOI：

  10.1021/jm00049a015

文献信息

• Tricyclic quinoxalinediones
  申请人：Sumitomo Pharmaceuticals Company, Limited

  公开号：US05616586A1

  公开（公告）日：1997-04-01

  Tricyclic quinoxalinediones of the formula: ##STR1## wherein X is alkyl, halogen, cyano, trifluoromethyl, nitro, hydroxy, amino, etc.; R.sup.1 is H, etc.; R.sup.2 is H, alkyl, cycloalkyl, alkenyl, alkynyl, cycloalkylalkyl, arylalkyl, substituted arylalkyl, aryl, or substituted aryl; W is H, CO.sub.2 R.sup.3, CO.sub.2 Y, CONR.sup.3 R.sup.4, CONR.sup.3 Y, CON(OR.sup.3)R.sup.4, COR.sup.3, CN, tetrazolyl, or substituted alkyl; R.sup.3 and R.sup.4 independently are H, alkyl, cycloalkyl, alkenyl, alkynyl, etc.; Y is mono-substituted alkyl or di-substituted alkyl; and n is an integer 0 or 1, or a pharmaceutically acceptable salt thereof, which are useful as a selective antagonist of glutamate receptor for the treatment or prevention of various diseases in animals including human being, for example, minimizing damage of central nervous system induced by ischaemic or hypoxylic conditions, treatment and/or prevention of neurodegenerative disorders, and further analgesics, antidepressants, anxiolitics, and anti-schizophrenics.

  公式为：##STR1## 其中X是烷基，卤素，氰基，三氟甲基，硝基，羟基，氨基等；R.sup.1是H等；R.sup.2是H，烷基，环烷基，烯基，炔基，环烷基烷基，芳基烷基，取代芳基烷基，芳基或取代芳基；W是H，CO.sub.2 R.sup.3，CO.sub.2 Y，CONR.sup.3 R.sup.4，CONR.sup.3 Y，CON(OR.sup.3)R.sup.4，COR.sup.3，CN，四唑基或取代烷基；R.sup.3和R.sup.4独立地是H，烷基，环烷基，烯基，炔基等；Y是单取代烷基或双取代烷基；n是整数0或1，或其药学上可接受的盐。它们可用作选择性谷氨酸受体拮抗剂，用于治疗或预防动物包括人类的各种疾病，例如减少缺血或低氧状况引起的中枢神经系统损伤，治疗和/或预防神经退行性疾病，以及镇痛剂，抗抑郁药，抗焦虑药和抗精神分裂症药物。
• TRICYCLIC QUINOXALINEDIONES AS GLUTAMATE RECEPTOR ANTAGONISTS
  申请人：SUMITOMO PHARMACEUTICALS COMPANY, LIMITED

  公开号：EP0642508A1

  公开（公告）日：1995-03-15
• US5616586A
  申请人：——

  公开号：US5616586A

  公开（公告）日：1997-04-01
• [EN] TRICYCLIC QUINOXALINEDIONES AS GLUTAMATE RECEPTOR ANTAGONISTS
  申请人：SUMITOMO PHARMACEUTICALS COMPANY, LIMITED

  公开号：WO1993008188A1

  公开（公告）日：1993-04-29

  (EN) Tricyclic quinoxalinediones of formula (1), wherein X is alkyl, halogen, cyano, trifluoromethyl, nitro, hydroxy, amino, etc.; R1 is H, etc.; R2 is H, alkyl, cycloalkyl, alkenyl, alkynyl, cycloalkylalkyl, arylalkyl, substituted arylalkyl, aryl, or substituted aryl; W is H, CO2R3, CO2Y, CONR3R4, CONR3Y, CON(OR3)R4, COR3, CN, tetrazolyl, or substituted alkyl; R3 and R4 independently are H, alkyl, cycloalkyl, alkenyl, alkynyl, etc.; Y is mono-substituted alkyl or di-substituted alkyl; and n is an integer 0 or 1, or a pharmaceutically acceptable salt thereof, which are useful as a selective antagonist of glutamate receptor for the treatment or prevention of various diseases in animals including human being, for example, minimizing damage of central nervous system induced by ischaemic or hypoxylic conditions, treatment and/or prevention of neurodegenerative disorders, and further analgesics, antidepressants, anxiolitics, and anti-schizophrenics.(FR) Quinoxalinediones tricycliques de la formule (1) dans laquelle X représente alkyle, halogène, cyano, trifluorométhyle, nitro, hydroxy, amino etc.; R1 représente H, etc.; R2 représente H, alkyle, cycloalkyle, alcényle, alkynyle, cycloalkylalkyle, arylalkyle, arylalkyle substitué, aryle, ou aryle substitué; W représente H, CO2R3, CO2Y, CONR3R4, CONR3Y, CON(OR3)R4, COR3, CN, tétrazolyle, ou alkyle substitué; R3 et R4 représentent indépendamment H, alkyle, cycloalkyle, alcényle, alkynyle, etc.; Y représente alkyle monosubstitué ou disubstitué; et n représente un nombre entier 0 ou 1, ou un de leurs sels pharmaceutiquement acceptables. Les quinoxalinediones de l'invention sont utiles comme antagonistes sélectifs de récepteur de glutamate dans le traitement ou la prévention de diverses maladies touchant l'animal ou l'homme, par exemple, réduisant la détérioration du système nerveux central induite par des états ischémiques ou hypoxyliques, dans le traitement et/ou la prévention de troubles neurodégénératifs, elles sont également utiles comme analgésiques, antidépresseurs, anxiolytiques et antischyzophréniques.
• Tricyclic Quinoxalinediones: 5,6-Dihydro-1H-pyrrolo[1,2,3-de]quinoxaline-2,3-diones and 6,7-Dihydro-1H,5H-pyrido[1,2,3-de]quinoxaline-2,3-diones as Potent Antagonists for the Glycine Binding Site of the NMDA Receptor
  作者：Ryu Nagata、Norihiko Tanno、Toru Kodo、Nobuyuki Ae、Hiroshi Yamaguchi、Tamiki Nishimura、Fujio Antoku、Tohru Tatsuno、Terufumi Kato

  DOI：10.1021/jm00049a015

  日期：1994.11

  A series of tricyclic quinoxalinediones, 5,6-dihydro-1H-pyrrolo[1,2,3-de]quinoxaline-2,3-diones and 6,7-dihydro-1H,5H-pyrido[1,2,3-de]quinoxaline-2,3-diones, were synthesized and was evaluated for their affinity for the glycine binding site of the NMDA receptor using a [H-3]- 5,7-dichlorokynurenic acid binding assay. The six-membered ring-fused tricyclic quinoxalinedione 18g (K-i = 9.9 nM) displayed high affinity for the glycine site. The anilide derivative 20g (K-i = 2.6 nM) was 4-fold more potent than 18g and as potent as L-689,560, one of the most potent glycine antagonists so far prepared. Although the carboxylic acid derivative of the corresponding five-membered ring-fused tricyclic quinoxalinedione 18e (K-i = 7.3 nM) had affinity comparable to that of 18g, the anilide derivative 20e largely decreased in the affinity in contrast to 20g. Enantiomers 23g, 24g, 25g, and 26g were prepared and tested. Only the S enantiomer 25g (K-i = 0.96 nM) retained the affinity among the anilide derivatives, whereas both enantiomers 23g (K-i = 2.3 nM) and 24g (K-i = 9.6 nM) were active among the carboxylic acid derivatives. The origin of the high affinity of carboxylic acid derivatives such as 18e and 18g would be a charge-charge interaction between the anionic carboxylate residues of the compounds and the cationic proton-donor site in the receptor.