2,3,6,7-tetrachloro-5-nitro-quinoxaline | 178619-87-9

• 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: 2,3,6,7-tetrachloro-5-nitro-quinoxaline
• 英文别名: 2,3,6,7-Tetrachloro-5-nitroquinoxaline；5-nitro-2,3,6,7-tetrachloroquinoxaline
• CAS: 178619-87-9
• 化学式: C₈HCl₄N₃O₂
• 分子量: 312.927
• InChiKey: GYQDMMSNDKWZLY-UHFFFAOYSA-N

物化性质

• 沸点：
  381.8±37.0 °C(Predicted)
• 密度：
  1.844±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  17
• 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：
  71.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,3,6,7-tetrachloro-5-nitro-quinoxaline 在 盐酸 、 bis(triphenylphosphine)palladium(II)-chloride 、 四溴化碳 、 氧气 、 臭氧 、 三苯基膦 、 lithium chloride 、 tin(ll) 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 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 43.75h， 生成 6,7-Dichloro-5-(1-imidazol-1-ylpropyl)-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 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以55%的产率得到2,3,6,7-tetrachloro-5-nitro-quinoxaline
  参考文献：
  名称：

  Unexpected regioselectivity in nitration of 3-aminoquinoxalin-2(1H )-ones †

  摘要：

  6,7-二取代-3-氨基喹喔啉-2(1H)-酮 3a-d 的第 8 位发生区域选择性硝化反应。 芳环和氨基上的取代基的电子效应或空间效应不会影响反应方向。 异构体 5-硝基衍生物 9 仅以迂回的方式由 3,6,7-三氯喹喔啉-2(1H)-酮 7 形成。 当第 8 位被占据时，5-硝基衍生物仅作为次要成分出现。 这些异构体通过 NMR 技术进行鉴定。 理论计算（AM1、Hartree-Fock、B3LYP）和 NMR 研究证实了假定的硝酸根阳离子对单质子化物 3ap 的攻击。

  DOI：

  10.1039/a910234p

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。
• Non-peptide GLP-1 agonists
  申请人：Teng Min

  公开号：US06927214B1

  公开（公告）日：2005-08-09

  Novel non-peptide GLP-1 agonists, pharmaceutical compositions comprising them, use of the non-peptide GLP-1 agonists for the preparation of pharmaceutical compositions and methods for the treatment and/or prevention of disorders and diseases wherein an activation of the human GLP-1 receptor is beneficial, especially metabolic disorders such as IGT, Type 1 diabetes, Type 2 diabetes and obesity.

  新型非肽类GLP-1激动剂，包括它们的药物组合物，使用非肽类GLP-1激动剂制备药物组合物以及治疗和/或预防激活人类GLP-1受体有益的疾病和疾病的方法，特别是代谢性疾病，如IGT、1型糖尿病、2型糖尿病和肥胖症。
• 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。
• 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。
• Cyanoiminoquinoxaline derivatives
  申请人：Shionogi & Co., Ltd.

  公开号：US06525054B1

  公开（公告）日：2003-02-25

  A cyanoiminoquinoxaline derivative of the formula (II) is useful as a preventive or therapeutic agent for diseases due to hyperexcitation of glutamate receptors. (wherein, X and Y each is independently O or NCN, provided that at least one of X and Y is NCN; R1, R2, R3, and R4 each is independently hydrogen, halogen, nitro, optionally substituted heterocyclic group etc.; R5 is hydrogen etc.; R1 and R2, R2 and R3, R3 and R4, and R4 and R5, each taken together with the adjacent atoms may form a carbocycle which may be substituted or may contain a heteroatom(s).)

  公式（II）的氰基亚氨基喹啉衍生物可用作预防或治疗由谷氨酸受体过度兴奋引起的疾病的药物。（其中，X和Y各自独立地为O或NCN，但至少其中之一为NCN；R1，R2，R3和R4各自独立地为氢，卤素，硝基，可选地取代的杂环基等；R5为氢等；R1和R2，R2和R3，R3和R4以及R4和R5，每组相邻的原子一起可能形成一个可取代或可能包含一个杂原子的碳环。)

表征谱图