6,7-二氯-2,3-二甲氧基-5-喹喔啉胺 | 178619-89-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 6,7-二氯-2,3-二甲氧基-5-喹喔啉胺
• 中文别名: N,N-二乙基-4-[2,5-二甲氧基-4-(4-硝基苯偶氮基)]苯偶氮基-3-(6-氟-4-甲氧基-1,3,5-三嗪-2-基)氨基苯胺；6,7-二氯-2,3-二甲氧基喹喔啉-5-胺
• 英文名称: 5-amino-6,7-dichloro-2,3-dimethoxy-quinoxaline
• 英文别名: 5-Amino-6,7-dichloro-2,3-dimethoxyquinoxaline；6,7-dichloro-2,3-dimethoxyquinoxalin-5-amine
• CAS: 178619-89-1
• 化学式: C₁₀H₉Cl₂N₃O₂
• 分子量: 274.106
• InChiKey: QCXRMHQLFIXXOV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  70.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6,7-二氯-2,3-二甲氧基-5-喹喔啉胺 在 吡啶 、 盐酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 生成 N-(6,7-dichloro-2,3-dimethoxyquinoxalin-5-yl)-methanesulphonamide
  参考文献：
  名称：

  Quinoxaline derivatives useful in therapy

  摘要：

  该发明提供了一种式为I的化合物，其中R.sup.1和R.sup.2独立地代表Cl或C.sub.1-6烷基；R.sup.3代表XCO.sub.2R.sup.4，XCONHSO.sub.2R.sup.5，YNHSO.sub.2R.sup.5或XR.sup.6；R.sup.4代表H或C.sub.1-6烷基（可选择地被芳基或杂环烷基取代）；R.sup.5代表CF.sub.3，杂环烷基或C.sub.1-6烷基（可选择地被芳基或杂环烷基取代）；R.sup.6代表酸性杂环；X代表C.sub.1-6烷基二自由基（可选择地被芳基或杂环烷基取代）；Y代表C.sub.2-6烷基二自由基（可选择地被芳基或杂环烷基取代）；前提是当R.sup.1和R.sup.2均代表Cl时，R.sup.3不代表CH.sub.2CO.sub.2H，CH.sub.2CO.sub.2CH.sub.3，CH.sub.2CH.sub.2NHSO.sub.2CF.sub.3或5-四唑甲基；以及其药学上可接受的盐。这些化合物被指示为抗焦虑剂，抗癫痫剂，镇痛剂和神经保护剂。

  公开号：

  US05863917A1
• 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 甲醇 、 乙酸乙酯 为溶剂， 反应 9.5h， 生成 6,7-二氯-2,3-二甲氧基-5-喹喔啉胺
  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

• 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 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.

  式(I)的化合物及其药学上可接受的盐，其中R.sup.1和R.sub.2各自独立地为Cl、Br、CH.sub.3、CH.sub.2 CH.sub.3或CF.sub.3；R.sup.3为H、CH.sub.3或CH.sub.2 CH.sub.3；X为通过氮原子连接的含有最多四个氮原子的5-成员杂环基团，该基团可选地被C.sub.1-C.sub.6烷基或(CH.sub.2).sub.nNR.sup.4R.sup.5取代，其中n是从1到5的整数，R.sup.4和R.sup.5各自独立地为H、C.sub.1-C.sub.6烷基、C.sub.3-C.sub.6环烷基或被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连接在一起，与连接的氮原子一起形成吡咯烷、哌嗪、哌嗪二氮杂环、N-(C.sub.1-C.sub.4烷基)哌嗪、吗啉或氮杂庚烷基团，或者当X为三唑基时，该基团可选地被苯并，是NMDA拮抗剂，对于急性神经退行性疾病的治疗具有价值，例如由中风或创伤性头部损伤引起的疾病，以及慢性神经系统疾病，例如老年性痴呆和阿尔茨海默病。
• N-(6,7-Dichloro-2,3-dioxo-1,2,3,4-tetrahydroquinoxalin-5-yl)-N-alkylsulfonamides as peripherally restricted N-methyl-d-aspartate receptor antagonists for the treatment of pain
  作者：Christopher Deur、Arun K. Agrawal、Heidi Baum、John Booth、Susan Bove、Joan Brieland、Amy Bunker、Cleo Connolly、Joseph Cornicelli、JoAnn Dumin、Barry Finzel、Xinmin Gan、Sheila Guppy、Gregg Kamilar、Kenneth Kilgore、Pil Lee、Cho-Ming Loi、Zhen Lou、Mark Morris、Laurence Philippe、Sally Przybranowski、Frank Riley、Brian Samas、Brian Sanchez、Haile Tecle、Ziqiang Wang、Kathryn Welch、Michael Wilson、Karen Yates

  DOI：10.1016/j.bmcl.2007.05.083

  日期：2007.8

  It has been hypothesized that peripherally restricted NMDA receptor antagonists may be effective analgesics for osteoarthritis pain. A class of novel quinoxalinedione atropisomers, first discovered for an NMDA receptor antagonist program for the treatment of stroke, was evaluated and further optimized with the goal of finding peripherally restricted NMDA receptor antagonists. (c) 2007 Elsevier Ltd. All rights reserved.
• Bioorg. Med. Chem. Lett. 2007, 17, 4599-4603
  作者：

  DOI：——

  日期：——
• QUINOXALINEDIONE NMDA RECEPTOR ANTAGONISTS
  申请人：Pfizer Limited

  公开号：EP0781279B1

  公开（公告）日：2001-06-13