5-methyl-2,3,6,7-tetrachloroquinoxaline | 178619-84-6

• 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-methyl-2,3,6,7-tetrachloroquinoxaline
• 英文别名: 2,3,6,7-tetrachloro-5-methylquinoxaline
• CAS: 178619-84-6
• 化学式: C₉H₄Cl₄N₂
• 分子量: 281.956
• InChiKey: GNPXKOGYRPEHPU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  25.8
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-methyl-2,3,6,7-tetrachloroquinoxaline 在 N-溴代丁二酰亚胺(NBS) 、 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile 作用下， 以 四氢呋喃 、 甲醇 、 三氯乙烷 、 水 、 异丙醇 为溶剂， 反应 6.0h， 生成 (6,7-Dichloro-2,3-dimethoxy-quinoxalin-5-yl)-acetonitrile
  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：

  2,3-diamino-5,6-dichlorotoluene 在 盐酸 、 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 反应 9.0h， 生成 5-methyl-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。
• Quinoxalinedione NMDA receptor antagonists
  申请人：Pfizer Inc.

  公开号：US05783572A1

  公开（公告）日：1998-07-21

  Compounds of formula (I): ##STR1## and their pharmaceutically acceptable salts, wherein R.sup.1 and R.sub.2 are each independently Cl, Br, CH.sub.3, CH.sub.2 CH.sub.3 or CF.sub.3 ; R.sup.3 is H, CH.sub.3 or CH.sub.2 CH.sub.3 ; and X is a 5-membered heterocyclic group containing up to four nitrogen atoms, attached via a nitrogen atom, the said group being optionally substituted by C.sub.1 -C.sub.6 alkyl or (CH.sub.2).sub.n NR.sup.4 R.sup.5, wherein n is an integer from 1 to 5 and R.sup.4 and R.sup.5 are each independently H, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 cycloalkyl or C.sub.1 -C.sub.4 alkyl substituted by phenyl or pyridyl, or R.sup.4 and R.sup.5 are linked to form, together with the nitrogen atom to which attached, a pyrrolidine, piperidine, piperazine, N-(C.sub.1 -C.sub.4 alkyl) piperazine, morpholine or azepine group, or, when X is triazolyl, said group may optionally be benzofused, are NMDA antagonists of value in the treatment of acute neurodegenerative disorders, e.g. arising from stroke or traumatic head injury and in chronic neurological disorders, e.g. senile dementia and Alzheimer's disease.

  公式(I)的化合物：##STR1##及其药用可接受的盐，其中R.sup.1和R.sub.2分别独立地为Cl、Br、CH.sub.3、CH.sub.2CH.sub.3或CF.sub.3；R.sup.3为H、CH.sub.3或CH.sub.2CH.sub.3；X为一个含有最多四个氮原子的5元杂环基，通过一个氮原子连接，该基可选择地被C.sub.1-C.sub.6烷基或(CH.sub.2).sub.nNR.sup.4R.sup.5取代，其中n为1至5的整数，R.sup.4和R.sup.5分别独立地为H、C.sub.1-C.sub.6烷基、C.sub.3-C.sub.6环烷基或由苯基或吡啶基取代的C.sub.1-C.sub.4烷基，或者R.sup.4和R.sup.5连接形成与连接的氮原子一起的吡咯烷、哌啶、哌嗪、N-(C.sub.1-C.sub.4烷基)哌嗪、吗啉或氮杂环基，或者当X为三唑基时，该基可选择地为苯并嵌合的，是一种在治疗急性神经退行性疾病中有价值的NMDA拮抗剂，例如由中风或创伤性头部损伤引起的疾病以及慢性神经疾病，例如老年性痴呆症和阿尔茨海默病。
• 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
• US5783572A
  申请人：——

  公开号：US5783572A

  公开（公告）日：1998-07-21