2,3-bis(bromomethyl)-6,7-difluoroquinoxaline | 143154-28-3

• 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-bis(bromomethyl)-6,7-difluoroquinoxaline
• 英文别名: 2,3-bis(bromomethyl)-6,7-difluoro-quinoxaline
• CAS: 143154-28-3
• 化学式: C₁₀H₆Br₂F₂N₂
• 分子量: 351.976
• InChiKey: VDIBCSVJRZHBFY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  16
• 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：
  25.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,3-bis(bromomethyl)-6,7-difluoroquinoxaline 在 盐酸 、 sodium 作用下， 以 甲苯 为溶剂， 反应 9.0h， 生成 α-amino-6,7-difluoro-3-(phosphonomethyl)-2-quinoxalinepropanoic acid hydrochloride
  参考文献：
  名称：

  Potent quinoxaline-spaced phosphono .alpha.-amino acids of the AP-6 type as competitive NMDA antagonists: synthesis and biological evaluation

  摘要：

  A series of alpha-amino-3-(phosphonoalkyl)-2-quinoxalinepropanoic acids was synthesized and evaluated for NMDA receptor affinity using a[H-3]CPP binding assay. Functional antagonism of the NMDA receptor complex was evaluated in vitro using a stimulated [H-3]TCP binding assay and in vivo by employing an NMDA-induced seizure model. Some analogues also were evaluated in the [H-3]-glycine binding assay. Several compounds of the AP-6 type show potent and selective NMDA antagonistic activity both in vitro and in vivo. In particular alpha-amino-7-chloro-3-(phosphonomethyl)-2-quinoxalinepropanoic acid (1) displayed an ED50 Of 1.1 mg/kg ip in the NMDA lethality model. Noteworthy is alpha-amino-6,7-dichloro-3-(phosphonomethyl)-2-quinoxalinepropanoic acid (3) with a unique dual activity, displaying in the NMDA receptor binding assay an IC50 of 3.4 nM and in the glycine binding assay an IC50 of 0.61 muM.

  DOI：

  10.1021/jm00055a004
• 作为产物：
  描述：

  4,5-二氟-2-硝基苯胺 在 盐酸 、 tin(ll) chloride 作用下， 以 苯 为溶剂， 反应 1.0h， 生成 2,3-bis(bromomethyl)-6,7-difluoroquinoxaline
  参考文献：
  名称：

  Potent quinoxaline-spaced phosphono .alpha.-amino acids of the AP-6 type as competitive NMDA antagonists: synthesis and biological evaluation

  摘要：

  A series of alpha-amino-3-(phosphonoalkyl)-2-quinoxalinepropanoic acids was synthesized and evaluated for NMDA receptor affinity using a[H-3]CPP binding assay. Functional antagonism of the NMDA receptor complex was evaluated in vitro using a stimulated [H-3]TCP binding assay and in vivo by employing an NMDA-induced seizure model. Some analogues also were evaluated in the [H-3]-glycine binding assay. Several compounds of the AP-6 type show potent and selective NMDA antagonistic activity both in vitro and in vivo. In particular alpha-amino-7-chloro-3-(phosphonomethyl)-2-quinoxalinepropanoic acid (1) displayed an ED50 Of 1.1 mg/kg ip in the NMDA lethality model. Noteworthy is alpha-amino-6,7-dichloro-3-(phosphonomethyl)-2-quinoxalinepropanoic acid (3) with a unique dual activity, displaying in the NMDA receptor binding assay an IC50 of 3.4 nM and in the glycine binding assay an IC50 of 0.61 muM.

  DOI：

  10.1021/jm00055a004

文献信息

• Quinoxaline phosphono-amino acids
  申请人：American Home Products Corporation

  公开号：US05118675A1

  公开（公告）日：1992-06-02

  The compounds of the formula: ##STR1## in which Q is the quinoxaline nucleus; m is one of the integers 0, 1 or 2; n is one of the integers 1,2 or 3; or a pharmaceutically acceptable salt, alkyl ester or ##STR2## where R.sup.3 and R.sup.4 are, independently, hydrogen, nitro, halo or methoxy, are NMDA antagonists useful in the treatment and prevention of central nervous system related pathological conditions resulting from overstimulation by excitatory amino acids.

  公式为：##STR1##的化合物中，其中Q是喹喔啉核；m是0、1或2中的一个整数；n是1、2或3中的一个整数；或是药学上可接受的盐、烷基酯或##STR2##，其中R.sup.3和R.sup.4分别为氢、硝基、卤素或甲氧基，是NMDA拮抗剂，可用于治疗和预防由兴奋性氨基酸过度刺激引起的中枢神经系统相关病理状况。
• US5118675A
  申请人：——

  公开号：US5118675A

  公开（公告）日：1992-06-02
• [EN] QUINOXALINE PHOSPHONO-AMINO ACIDS
  申请人：——

  公开号：WO1992014740A1

  公开（公告）日：1992-09-03

  [FR] On décrit des composés de la formule (I) où Q représente le noyau de quinoxaline; m représente l'un des nombres entiers 0, 1 ou 2; n représente l'un des nombres entiers 1, 2 ou 3; ou un sel pharmaceutiquement acceptable, un ester d'alkyle ou (II) où R3 et R4 représentent indépendamment hydrogène, nitro, halo ou méthoxy. Ces composés sont des antagonistes de N-méthyle-D-Aspartate pouvant être utilisés pour le traitement et la prévention d'états pathologiques associés au système nerveux central et produits par une stimulation excessive des aminoacides excitateurs.
  [EN] The compounds of formula (I), in which Q is the quinoxaline nucleus; m is one of the integers 0, 1 or 2; n is one of the integers 1, 2 or 3; or a pharmaceutically acceptable salt, alkyl ester or (II) where R?3 and R?4 are, independently, hydrogen, nitro, halo or methoxy, are NMDA antagonists useful in the treatment and prevention of central nervous system related pathological conditions resulting from overstimulation by excitatory amino acids.
• Potent quinoxaline-spaced phosphono .alpha.-amino acids of the AP-6 type as competitive NMDA antagonists: synthesis and biological evaluation
  作者：Reinhardt B. Baudy、Lynne P. Greenblatt、Ivo L. Jirkovsky、Mary Conklin、Ralph J. Russo、Donna R. Bramlett、Tracy A. Emrey、Joanne T. Simmonds、Dianne M. Kowal

  DOI：10.1021/jm00055a004

  日期：1993.2

  A series of alpha-amino-3-(phosphonoalkyl)-2-quinoxalinepropanoic acids was synthesized and evaluated for NMDA receptor affinity using a[H-3]CPP binding assay. Functional antagonism of the NMDA receptor complex was evaluated in vitro using a stimulated [H-3]TCP binding assay and in vivo by employing an NMDA-induced seizure model. Some analogues also were evaluated in the [H-3]-glycine binding assay. Several compounds of the AP-6 type show potent and selective NMDA antagonistic activity both in vitro and in vivo. In particular alpha-amino-7-chloro-3-(phosphonomethyl)-2-quinoxalinepropanoic acid (1) displayed an ED50 Of 1.1 mg/kg ip in the NMDA lethality model. Noteworthy is alpha-amino-6,7-dichloro-3-(phosphonomethyl)-2-quinoxalinepropanoic acid (3) with a unique dual activity, displaying in the NMDA receptor binding assay an IC50 of 3.4 nM and in the glycine binding assay an IC50 of 0.61 muM.