7-fluoro-1,2,3,4-tetrahydro-1-isopropyl-2,3-dioxoquinoxaline | 151448-19-0

• 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: 7-fluoro-1,2,3,4-tetrahydro-1-isopropyl-2,3-dioxoquinoxaline
• 英文别名: 6-fluoro-4-propan-2-yl-1H-quinoxaline-2,3-dione
• CAS: 151448-19-0
• 化学式: C₁₁H₁₁FN₂O₂
• 分子量: 222.219
• InChiKey: ITBOGCCLEALMOQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-fluoro-1,2,3,4-tetrahydro-1-isopropyl-2,3-dioxoquinoxaline 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 4.25h， 生成 7-Fluoro-3-phenyl-5-propan-2-ylimidazo[1,5-a]quinoxalin-4-one
  参考文献：
  名称：

  3-Phenyl-Substituted Imidazo[1,5-a]quinoxalin-4-ones and Imidazo[1,5-a]quinoxaline Ureas That Have High Affinity at the GABA_A/Benzodiazepine Receptor Complex

  摘要：

  A series of imidazo[1,5-alpha]quinoxalin-4-ones and imidazo[1,5-alpha]quinoxaline ureas containing substituted phenyl groups at the 3-position was developed. Compounds within the imidazo-[1,5-alpha]quinoxaline urea series had high affinity for the GABA(A)/benzodiazepine receptor complex with varying in vitro efficacy, although most analogs were partial agonists as indicated by [S-35]TBPS and Cl- current ratios. Interestingly, a subseries of piperazine ureas was identified which had biphasic efficacy, becoming more antagonistic with increasing concentration. Analogs within the imidazo [1,5-alpha] quinoxalin-4-one series had substantially decreased binding affinity as compared to the quinoxaline urea series. These compounds ranged from antagonists to full agonists by in. vitro analysis, with several derivatives having roughly 4-fold greater intrinsic activity than diazepam as indicated by Cl- current measurement. Numerous compounds from both series were effective in antagonizing metrazole-induced seizures, consistent with anti-convulsant properties and possible anxiolytic activity. Most of the quinoxaline ureas and quinoxalin-4-ones were active in an acute electroshock physical dependence side effect assay in mice precluding further development.

  DOI：

  10.1021/jm960070+
• 作为产物：
  描述：

  2-溴-4-氟-1-硝基苯 在 palladium on activated charcoal 氢气 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 80.0h， 生成 7-fluoro-1,2,3,4-tetrahydro-1-isopropyl-2,3-dioxoquinoxaline
  参考文献：
  名称：

  3-Phenyl-Substituted Imidazo[1,5-a]quinoxalin-4-ones and Imidazo[1,5-a]quinoxaline Ureas That Have High Affinity at the GABA_A/Benzodiazepine Receptor Complex

  摘要：

  A series of imidazo[1,5-alpha]quinoxalin-4-ones and imidazo[1,5-alpha]quinoxaline ureas containing substituted phenyl groups at the 3-position was developed. Compounds within the imidazo-[1,5-alpha]quinoxaline urea series had high affinity for the GABA(A)/benzodiazepine receptor complex with varying in vitro efficacy, although most analogs were partial agonists as indicated by [S-35]TBPS and Cl- current ratios. Interestingly, a subseries of piperazine ureas was identified which had biphasic efficacy, becoming more antagonistic with increasing concentration. Analogs within the imidazo [1,5-alpha] quinoxalin-4-one series had substantially decreased binding affinity as compared to the quinoxaline urea series. These compounds ranged from antagonists to full agonists by in. vitro analysis, with several derivatives having roughly 4-fold greater intrinsic activity than diazepam as indicated by Cl- current measurement. Numerous compounds from both series were effective in antagonizing metrazole-induced seizures, consistent with anti-convulsant properties and possible anxiolytic activity. Most of the quinoxaline ureas and quinoxalin-4-ones were active in an acute electroshock physical dependence side effect assay in mice precluding further development.

  DOI：

  10.1021/jm960070+

文献信息

• [EN] 3-SUBSTITUTED IMIDAZO (1,5-a) AND IMIDAZO (1,5-a)-TRIAZOLO (1,5-c) QUINOXALINES AND QUINAZOLINES WITH CNS ACTIVITY
  申请人：THE UPJOHN COMPANY

  公开号：WO1993012113A1

  公开（公告）日：1993-06-24

  (EN) An oxoimidazo(1,5-a)quinoxaline and a oxoimidazo(1,5-a)quinazoline of formula (I), an imidazo(1,5-a)-1,2,4-triazolo-(4,3-c)quinazoline and an imidazo(1,5-a)-1,2,4-triazolo-(4,3-c)quinozoline of formula (II), and an imidazo(1,5-a)quinoxaline of formula (III). The R-groups and other variables are as defined herein. The compounds are useful in the treatment of central nervous system disorders associated with the benzodiazepine receptors in a subject in need of such treatment comprising administering to the subject a therapeutically-effective amount of a formula I, II, or III compound for alleviation of such disorder. Typically, the compound of formula I, II, or III is administered in the form of a pharmaceutical composition comprising a pharmaceutically-acceptable carrier or diluent.(FR) L'invention se rapporte à une oxoimidazo(1,5-a)quinoxaline et à une oxoimidazo(1,5-a)quinazoline de la formule (I), à une imidazo(1,5-a)-1,2,4-triazolo-(4,3-c)quinazoline et à une imidazo(1,5-a)-1,2,4-triazolo-(4,3-c)quinozoline de la formule (II), et ainsi qu'à une imidazo(1,5-a)quinoxaline de la formule (III), les groupes R et autres variables ont la notation ci-incluse. Les composés sont utiles dans le traitement des troubles du système nerveux central associé aux récepteurs de benzodiazépine chez un sujet nécessitant un traitement qui consiste à lui administrer une quantité thérapeutiquement efficace d'un composé des formules I, II ou III en vue d'atténuer ces troubles. Généralement, le composé des formules I, II ou III est administré sous la forme d'une composition pharmaceutique comprenant un excipient ou diluant pharmaceutiquement acceptable.
• 3-Phenyl-Substituted Imidazo[1,5-<i>a</i>]quinoxalin-4-ones and Imidazo[1,5-<i>a</i>]quinoxaline Ureas That Have High Affinity at the GABA_A/Benzodiazepine Receptor Complex
  作者：E. Jon Jacobsen、Lindsay S. Stelzer、Kenneth L. Belonga、Donald B. Carter、Wha Bin Im、Vimala H. Sethy、Andrew H. Tang、Philip F. VonVoigtlander、James D. Petke

  DOI：10.1021/jm960070+

  日期：1996.1.1

  A series of imidazo[1,5-alpha]quinoxalin-4-ones and imidazo[1,5-alpha]quinoxaline ureas containing substituted phenyl groups at the 3-position was developed. Compounds within the imidazo-[1,5-alpha]quinoxaline urea series had high affinity for the GABA(A)/benzodiazepine receptor complex with varying in vitro efficacy, although most analogs were partial agonists as indicated by [S-35]TBPS and Cl- current ratios. Interestingly, a subseries of piperazine ureas was identified which had biphasic efficacy, becoming more antagonistic with increasing concentration. Analogs within the imidazo [1,5-alpha] quinoxalin-4-one series had substantially decreased binding affinity as compared to the quinoxaline urea series. These compounds ranged from antagonists to full agonists by in. vitro analysis, with several derivatives having roughly 4-fold greater intrinsic activity than diazepam as indicated by Cl- current measurement. Numerous compounds from both series were effective in antagonizing metrazole-induced seizures, consistent with anti-convulsant properties and possible anxiolytic activity. Most of the quinoxaline ureas and quinoxalin-4-ones were active in an acute electroshock physical dependence side effect assay in mice precluding further development.