1-tert-butyl-1,2,3,4-tetrahydro-2,3-dioxo-quinoxaline | 129799-91-3

• 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: 1-tert-butyl-1,2,3,4-tetrahydro-2,3-dioxo-quinoxaline
• 英文别名: 1-tert-butyl-1,2,3,4-tetrahydro-2,3-dioxoquinoxaline；1-(tert-butyl)-tetrahydroquinoxalin-2,3-dione；4-tert-butyl-1H-quinoxaline-2,3-dione
• CAS: 129799-91-3
• 化学式: C₁₂H₁₄N₂O₂
• 分子量: 218.255
• InChiKey: FXDQDXHXTKKZDO-UHFFFAOYSA-N

物化性质

• 密度：
  1.195±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-tert-butyl-1,2,3,4-tetrahydro-2,3-dioxo-quinoxaline 在 dimethyl sulfide borane 、 potassium tert-butylate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 103.25h， 生成 (3,5-dimethylpiperazin-1-yl)-[3-(4-fluorophenyl)-4H-imidazo[1,5-a]quinoxalin-5-yl]methanone
  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：

  1-溴-2-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 1-tert-butyl-1,2,3,4-tetrahydro-2,3-dioxo-quinoxaline
  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

• Imidazo[1,5-A]quinoxalines
  申请人：The Upjohn Company

  公开号：US05541324A1

  公开（公告）日：1996-07-30

  An invention relating to Imidazo[1,5-a]quinoxalines (I) ##STR1## which do not contain an endocyclic carbonyl group and which are useful as anxiolytic and sedative/hypnotic agents.

  一种涉及咪唑并[1,5-a]喹喔啉(I)的发明，不含内环羰基，并且可用作抗焦虑和镇静/催眠剂。
• Chemical process for the preparation of imidazo-quinoxalines and
  申请人：Novo Nordisk A/S

  公开号：US04999353A1

  公开（公告）日：1991-03-12

  The invention relates to a dealkylation chemical process for preparing imidazoquinoxalines bearing hydrogen substitution in the five position, and to valuable pharm-intermediates of the formula I ##STR1## wherein ##STR2## wherein R' is C.sub.1-6 -alkyl, C.sub.3-7 -cycloalkyl, phenyl, thienyl, or C.sub.1-3 -alkoxymethyl and wherein R.sup.6 and R.sup.7 independently are hydrogen,halogen or CF.sub.3, used in that process. The intermediates also have anticonvulsant and anxiolytic properties.

  本发明涉及一种去烷基化化学过程，用于制备在五位带有氢取代的咪唑喹啉化合物，并且涉及公式I的有价值的药物中间体：##STR1## 其中：##STR2## 其中R'是C.sub.1-6烷基，C.sub.3-7环烷基，苯基，噻吩基或C.sub.1-3-烷氧甲基，R.sup.6和R.sup.7独立地为氢，卤素或CF.sub.3，用于该过程。这些中间体还具有抗惊厥和抗焦虑的特性。
• Imidazoquinoxalines and their preparation and use
  申请人：Novo Nordisk A/S

  公开号：US05116841A1

  公开（公告）日：1992-05-26

  New imidazoquinoxaline compounds having the general formula I ##STR1## wherein ##STR2## wherein R.sup.1 and R.sup.2 independently are hydrogen, straight or branched C.sub.1-6 -alkyl, or C.sub.3-7 -cycloalkyl; R.sup.3 is hydrogen, straight or branched C.sub.1-6 -alkyl, straight or branched C.sub.2-6 -alkenyl, or aralkyl or aroylalkyl which may optionally be substituted with halogen or C.sub.1-6 -alkoxy; R.sup.4 amd R.sup.5 independently are hydrogen, halogen, C.sub.1-6 -alkyl or trifluoromethyl. The compounds are useful in psychopharmaceutical preparations as anticonvulsants, anxiolytics, hypnotics and in improving the cognitive function of the brain of mammals.

  新的咪唑并喹啉化合物具有通式I ##STR1## 其中 ##STR2## 其中R.sup.1和R.sup.2独立地是氢、直链或支链C.sub.1-6烷基，或C.sub.3-7环烷基；R.sup.3是氢、直链或支链C.sub.1-6烷基、直链或支链C.sub.2-6烯基，或芳基烷基或芳基酰基烷基，它们可以选择性地被卤素或C.sub.1-6烷氧基取代；R.sup.4和R.sup.5独立地是氢、卤素、C.sub.1-6烷基或三氟甲基。这些化合物在心理药物制剂中作为抗癫痫、抗焦虑、催眠剂以及改善哺乳动物大脑的认知功能方面具有用途。
• Imidazoquinoxalines and their preparation
  申请人：NOVO NORDISK A/S

  公开号：EP0368652A1

  公开（公告）日：1990-05-16

  A novel chemical process for preparing imidazoquinoxalines bearing hydrogen substitution in the 5-position comprises dealkylation of the novel corresponding 5-tert-butyl compound (which also has vaulable pharmacological properties).

  制备在 5 位上有氢取代位的咪唑喹喔啉的新型化学工艺包括对新型相应的 5-叔丁基化合物（也具有重要的药理特性）进行脱烷基化。
• Milbemycin ether derivatives, their preparation and their therapeutic and agrochemical uses
  申请人：Sankyo Company Limited

  公开号：EP0448243A1

  公开（公告）日：1991-09-25

  Compounds of formula (I): in which: R¹ is a variety of organic groups; R² is hydrogen, halogen, cyano, nitro, optionally substituted alkyl, alkoxy, alkoxyalkoxy, or a group of formula: (CH₂)nNHR⁹ (CH₂)nNR⁹COR⁶ (CH₂)nNR⁹COCOR⁶ (CH₂)nNR⁹COCOOR⁷ (CH₂)nNR⁹CHR⁶NHCOR⁶ (CH₂)nNR⁹CHR⁶NHCONHR⁶ (CH₂)nNR⁹CHR⁶NHCOOR⁷ (CH₂)nNR⁹C(=Y)YR⁶ (CH₂)nNR⁹C(=Y)NR⁶R⁶ (CH₂)nNR⁹C(=Y)NR⁶NR⁶R⁶ (CH₂)nNR⁹C(=Y)NR⁶NHZ (CH₂)nNR⁹C(=NR¹⁰)NHR¹⁰ (CH₂)nNR⁹C(=NR¹⁰)R⁶ or (CH₂)nNR⁹SOmR⁶ (in which m is 1 or 2; n is 0, 1 or 2; R⁶ is a variety of organic groups; R⁷ is alkyl, cycloalkyl, or aralkyl; R⁹ is hydrogen or alkyl; R¹⁰ is any of R⁶, or cyano, nitro, -COOR⁷, or -COR⁶; Y is oxygen or sulphur; Z is -COOR⁷, -COR⁶ or -SO₂R⁶); Q is methylene, ethylene or -OCH₂-; P is methylene, ethylene, oxygen or a single bond; V and W each represents methylene, carbonyl or thiocarbonyl; R³ and R⁴ are hydrogen, alkyl or alkoxy; R¹¹ is alkyl, alkoxy, alkylthio, alkanoyloxy, alkoxycarbonyl, halogen, cyano, nitro, amino, mono- or di- alkylamino, carbamoyl, mono- or di- alkylcarbamoyl, or alkanoylamino; R¹² is hydrogen or alkyl; R¹³ is alkyl; R⁵ is methyl, ethyl, isopropyl or sec-butyl; and X is hydroxy, alkanoyloxy or hydroxyimino] and salts and esters thereof have valuable anthelmintic, acaricidal and insecticidal activities. Methods of preparing the compounds are also provided.

  式(I)化合物： 其中R¹ 是各种有机基团；R² 是氢、卤素、氰基、硝基、任选取代的烷基、烷氧基、烷氧基烷氧基或式基团： (CH₂)nNHR⁹ (CH₂)nNR⁹COR⁶ (CH₂)nNR𠞙COCOR⁶ (CH₂)nNR𠞙COCOOR⁷ (CH₂)nNR𠞙CHR⁶NHCOR⁶ (CH₂)nNR𠞙CHR⁶NHCONHR⁶ (CH₂)nNR𠞙CHR⁶NHCOOR⁷ (CH₂)nNR𠞙C(=Y)YR⁶ (CH₂)nNR𠞙C(=Y)NR⁶R⁶ (CH₂)nNR𠞙C(=Y)NR⁶NR⁶R⁶ (CH₂)nNR𠞙C(=Y)NR⁶NHZ (CH₂)nNR𠞙C(=NR¹⁰)NHR¹⁰ (CH₂)nNR𠞙C(=NR¹⁰)R⁶ 或 (CH₂)nNR𠞙SOmR⁶ (其中 m 是 1 或 2；n 是 0、1 或 2；R⁶ 是各种有机基团；R⁷ 是烷基、环烷基或芳烷基；R⁹ 是氢或烷基；R¹⁰ 是 R⁶、氰基、硝基、-COR⁷ 或 -COR⁶ 中的任意一个；Y 是氧或硫；Z 是-COOR⁷、-COR⁶ 或-SO₂R⁶)；Q 是亚甲基、亚乙基或-OCH₂-；P 是亚甲基、亚乙基、氧或单键；V 和 W 各自代表亚甲基、羰基或硫代羰基；R³ 和 R⁴ 是氢、烷基或烷氧基；R¹¹ 是烷基、烷氧基、烷硫基、烷酰氧基、烷氧羰基、卤素、氰基、硝基、氨基、单或双烷基氨基、氨基甲酰基、单或双烷基氨基甲酰基或烷酰氨基；R¹² 是氢或烷基；R¹³ 是烷基；R⁵ 是甲基、乙基、异丙基或仲丁基；X 是羟基、烷酰氧基或羟基亚氨基]及其盐和酯具有重要的驱虫、杀螨剂和杀虫剂活性。此外，还提供了制备这些化合物的方法。