5-amino-2,3,6,7-tetrachloroquinoxaline | 178619-88-0

• 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: 5-amino-2,3,6,7-tetrachloroquinoxaline
• 英文别名: 2,3,6,7-tetrachloroquinoxalin-5-amine
• CAS: 178619-88-0
• 化学式: C₈H₃Cl₄N₃
• 分子量: 282.944
• InChiKey: DXXBFAXBSVZRKA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  51.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-amino-2,3,6,7-tetrachloroquinoxaline 在 盐酸 、 bis(triphenylphosphine)palladium(II)-chloride 、 四溴化碳 、 氧气 、 臭氧 、 三苯基膦 、 lithium chloride 、 sodium nitrite 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醚 、 二氯甲烷 、 氯仿 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 37.75h， 生成 6,7-Dichloro-5-[1-(1,2,4-triazol-1-yl)propyl]-1,4-dihydroquinoxaline-2,3-dione
  参考文献：
  名称：

  Structure−Activity Relationships of 1,4-Dihydro-(1H,4H)-quinoxaline-2,3-diones as N-Methyl-d-aspartate (Glycine Site) Receptor Antagonists. 1. Heterocyclic Substituted 5-Alkyl Derivatives

  摘要：

  A series of 6,7-dichloro-1,4-dihydro-(1H, 4H)-quinoxaline-2,3-diones (1-17) were prepared in which the 5-position substituent was a heterocyclylmethyl or 1-(heterocyclyl)-1-propyl group. Structure-activity relationships were evaluated where binding affinity for the glycine site of the N-methyl-D-aspartate (NMDA) receptor was measured using the specific radioligand [H-3]- L-689,560, and functional antagonism was demonstrated by inhibition of NMDA-induced depolarizations of rat cortical wedges. The ability to prevent NMDA-induced hyperlocomotion in mice in vivo was measured for selected compounds. Binding affinity increased significantly if the heterocyclic group, e.g. 1,2,3-triazol-1-yl could participate in accepting a hydrogen bond from the receptor. It was difficult to obtain compounds with adequate aqueous solubility and strategies to improve it were investigated. The most potent compound in this series, 6,7-dichloro-5-[1-( 1,2,4-triazol-4-yl)propyl]-1,4-dihydro-(1H, 4H)-quinoxaline-2,3-dione (17) (binding IC50 = 2.6 nM; cortical wedge EC50 = 90 nM), inhibited NMDA-induced hyperlocomotion in mice (6/9 protected at 20 mg/kg iv). Pharmacokinetic parameters, including extent of brain penetration, for 11 and 17 are reported.

  DOI：

  10.1021/jm001124p
• 作为产物：
  描述：

  利可替奈 在 氯化亚砜 、 N,N-二甲基甲酰胺 、 tin(ll) chloride 作用下， 以 乙酸乙酯 为溶剂， 反应 9.0h， 生成 5-amino-2,3,6,7-tetrachloroquinoxaline
  参考文献：
  名称：

  Structure−Activity Relationships of 1,4-Dihydro-(1H,4H)-quinoxaline-2,3-diones as N-Methyl-d-aspartate (Glycine Site) Receptor Antagonists. 1. Heterocyclic Substituted 5-Alkyl Derivatives

  摘要：

  A series of 6,7-dichloro-1,4-dihydro-(1H, 4H)-quinoxaline-2,3-diones (1-17) were prepared in which the 5-position substituent was a heterocyclylmethyl or 1-(heterocyclyl)-1-propyl group. Structure-activity relationships were evaluated where binding affinity for the glycine site of the N-methyl-D-aspartate (NMDA) receptor was measured using the specific radioligand [H-3]- L-689,560, and functional antagonism was demonstrated by inhibition of NMDA-induced depolarizations of rat cortical wedges. The ability to prevent NMDA-induced hyperlocomotion in mice in vivo was measured for selected compounds. Binding affinity increased significantly if the heterocyclic group, e.g. 1,2,3-triazol-1-yl could participate in accepting a hydrogen bond from the receptor. It was difficult to obtain compounds with adequate aqueous solubility and strategies to improve it were investigated. The most potent compound in this series, 6,7-dichloro-5-[1-( 1,2,4-triazol-4-yl)propyl]-1,4-dihydro-(1H, 4H)-quinoxaline-2,3-dione (17) (binding IC50 = 2.6 nM; cortical wedge EC50 = 90 nM), inhibited NMDA-induced hyperlocomotion in mice (6/9 protected at 20 mg/kg iv). Pharmacokinetic parameters, including extent of brain penetration, for 11 and 17 are reported.

  DOI：

  10.1021/jm001124p

文献信息

• Quinoxaline derivatives useful in therapy
  申请人：Pfizer Inc.

  公开号：US05852016A1

  公开（公告）日：1998-12-22

  Compounds of formula (I), wherein A represents N or CH; R.sup.1 and R.sup.2 independently represent C.sup.1-4 alkyl, halo or CF.sub.3 ; R.sup.3 represents C.sub.1-4 alkyl (optionally substituted), C.sub.3-7 cycloalkyl, CF.sub.3 or aryl; R.sup.4 represents H, C.sub.3-7 cycloalkyl or C.sub.1-6 alkyl (optionally substituted); and their pharmaceutically acceptable derivatives; are useful in the treatment of, inter alia, neurodogenerative disorders. ##STR1##

  式（I）的化合物，其中A代表N或CH；R.sup.1和R.sup.2分别代表C.sup.1-4烷基，卤素或CF.sub.3；R.sup.3代表C.sub.1-4烷基（可选取代），C.sub.3-7环烷基，CF.sub.3或芳基；R.sup.4代表H，C.sub.3-7环烷基或C.sub.1-6烷基（可选取代）；以及它们的药学上可接受的衍生物；在治疗神经退行性疾病等方面是有用的。
• Quinoxalinediones
  申请人：Pfizer Inc

  公开号：US06333326B1

  公开（公告）日：2001-12-25

  This invention relates to 2,3(1H,4H)-quinoxalinedione derivatives which are selective antagonists of N-methyl-D-aspartate receptors. More particularly, this invention relates to 5-triazolyl-2,3(1H,4H)-quinoxalinedione derivatives and to the preparation of, compositions containing, and the uses of, such derivatives. It also relates to a method for treating acute neurodegeneration disorders and chronic neurological disorders.

  这项发明涉及选择性N-甲基-D-天冬氨酸受体拮抗剂的2,3(1H,4H)-喹诺酮二酮衍生物。更具体地说，该发明涉及5-三唑基-2,3(1H,4H)-喹诺酮二酮衍生物的制备、含有这些衍生物的组合物以及这些衍生物的用途。它还涉及一种治疗急性神经退行性疾病和慢性神经疾病的方法。
• QUINOXALINEDIONE NMDA RECEPTOR ANTAGONISTS
  申请人：Pfizer Limited

  公开号：EP0781279A1

  公开（公告）日：1997-07-02
• QUINOXALINE DERIVATIVES USEFUL IN THERAPY
  申请人：Pfizer Limited

  公开号：EP0783495B1

  公开（公告）日：2002-02-27
• QUINOXALINEDIONES
  申请人：Pfizer Research and Development Company, N.V./S.A.

  公开号：EP0885212A1

  公开（公告）日：1998-12-23