2,3-dimethyl-6-(N,N-dimethylaminoethyl)-6H-indolo(2,3-b)quinoxaline | 112228-65-6

• 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-dimethyl-6-(N,N-dimethylaminoethyl)-6H-indolo(2,3-b)quinoxaline
• 英文别名: 2,3-dimethyl-6-(2-dimethylaminoethyl)-6H-indolo[2,3-b]quinoxaline；6-(N,N-dimethylaminoethyl)-2,3-dimethylindolo[2,3-b]quinoxaline；B-220；6H-Indolo(2,3-b)quinoxaline-6-ethanamine, N,N,2,3-tetramethyl-；2-(2,3-dimethylindolo[3,2-b]quinoxalin-6-yl)-N,N-dimethylethanamine
• CAS: 112228-65-6
• 化学式: C₂₀H₂₂N₄
• 分子量: 318.421
• InChiKey: FPLSGFJELWCFTH-UHFFFAOYSA-N

物化性质

• 熔点：
  134-136 °C
• 沸点：
  518.8±50.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  34
• 氢给体数：
  0
• 氢受体数：
  3

制备方法与用途

生物活性

B220 是一种能抑制 HSV-1、HSV-2 和人巨细胞病毒 (CMV) 生长的抗病毒剂。

靶点

体外研究显示，B220 通过抑制中性粒细胞释放活性氧物种以及细胞内活性氧物种生成来发挥其作用。这种抑制并非通过 B220 直接清除自由基的活性实现的，也不影响组装氧化酶的功能。此外，B220 还会降低中性粒细胞吞噬荧光标记的血小板酵母细胞的能力，并使预孵育于 10 µg/mL B220 的细胞在受刺激时表面 C3 受体的动员数量减少。

反应信息

• 作为反应物：
  描述：

  2,3-dimethyl-6-(N,N-dimethylaminoethyl)-6H-indolo(2,3-b)quinoxaline 在 盐酸 作用下， 以 水 、 丙酮 为溶剂， 以89%的产率得到2,3-dimethyl-6-(2-dimethylaminoethyl)-6H-indolo[2,3-b]quinoxaline hydrochloride
  参考文献：
  名称：

  Interactions of Antiviral Indolo[2,3-b]quinoxaline Derivatives with DNA

  摘要：

  Here, we present the synthesis of five novel indoloquinoxaline derivatives and investigate the DNA binding properties of these monomeric as well as dimeric compounds using absorption, fluorescence, and linear dichroism. Several of the mono- and dicationic derivatives presented have previously demonstrated an excellent antiviral effect that is higher than already acknowledged agents against human cytomegalovirus (CMV), herpes simplex virus type 1 (HSV-1), and varicella-zoster virus (VZV). We find that the DNA binding constants of the monomeric and dimeric derivatives are high (similar to 10(6)) and very high (similar to 10(9)) respectively. Results from the spectroscopic measurements show that the planar aromatic indoloquinoxaline moieties upon interaction with DNA intercalate between the nucleobases. Furthermore, we use poly(dA-dT)(2) and calf thymus DNA in a competitive binding experiment to show that all our derivatives have an wAT-region preference. The findings are important in the understanding of the antiviral effect of these derivatives and give invaluable information for the future optimization of the DNA binding properties of this kind of drugs.

  DOI：

  10.1021/jm800787b
• 作为产物：
  描述：

  二甲氨基氯乙烷盐酸 、 2,3-dimethyl-6H-indolo[2,3-b]quinoxaline 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 24.0h， 以72%的产率得到2,3-dimethyl-6-(N,N-dimethylaminoethyl)-6H-indolo(2,3-b)quinoxaline
  参考文献：
  名称：

  Interactions of Antiviral Indolo[2,3-b]quinoxaline Derivatives with DNA

  摘要：

  Here, we present the synthesis of five novel indoloquinoxaline derivatives and investigate the DNA binding properties of these monomeric as well as dimeric compounds using absorption, fluorescence, and linear dichroism. Several of the mono- and dicationic derivatives presented have previously demonstrated an excellent antiviral effect that is higher than already acknowledged agents against human cytomegalovirus (CMV), herpes simplex virus type 1 (HSV-1), and varicella-zoster virus (VZV). We find that the DNA binding constants of the monomeric and dimeric derivatives are high (similar to 10(6)) and very high (similar to 10(9)) respectively. Results from the spectroscopic measurements show that the planar aromatic indoloquinoxaline moieties upon interaction with DNA intercalate between the nucleobases. Furthermore, we use poly(dA-dT)(2) and calf thymus DNA in a competitive binding experiment to show that all our derivatives have an wAT-region preference. The findings are important in the understanding of the antiviral effect of these derivatives and give invaluable information for the future optimization of the DNA binding properties of this kind of drugs.

  DOI：

  10.1021/jm800787b

文献信息

• Reduction of indolo[2,3-b]quinoxalines
  作者：Robert Engqvist、Birgitta Stensland、Jan Bergman

  DOI：10.1016/j.tet.2005.02.060

  日期：2005.5

  indolo[2,3-b]quinoxalines with zinc in the presence of an anhydride gave N,N-diacyl trapped 6,11-dihydroindolo[2,3-b]quinoxalines in 43–92% yields. When the reduction with zinc was performed in TFA/TFAA, an unexpected ring opened product was isolated in 49% yield. The structure of this product could be identified as 1,2-dihydro-1-trifluoroacetyl-3-[(2-trifluoroacetylamino)phenyl]quinoxaline.

  吲哚并[2,3-的减少b ]喹喔啉与在酸酐的存在下，得到锌Ñ，N-二酰基被困-6,11-二氢吲哚并[2,3- b ]喹喔啉在43-92％的产率。当在TFA / TFAA中用锌还原时，分离出意外的开环产物，产率为49％。该产物的结构可以鉴定为1,2-二氢-1-三氟乙酰基-3-[（2-三氟乙酰氨基）苯基]喹喔啉。
• [EN] ALKYL SUBSTITUTED INDOLOQUINOXALINES<br/>[FR] INDOLOQUINOXALINES ALKYL-SUBSTITUEES
  申请人：OXYPHARMA AB

  公开号：WO2005123741A1

  公开（公告）日：2005-12-29

  Novel substituted indoloquinoxalines of formula (I R2 (I) Y Wherein R1 is hydrogen or represents one or more similar or different substituents in the positions 7 to 10 selected from the group halogen, lower alkyl/alkoxy, hydroxy, trifluoromethyl, trichloromethyl, trifluoromethoxy, R2 represents similar or different C1-C4 alkyl substituents, X is CO or CH2, Y is OH, NH2, NH-(CH2)n-R3 wherein R3 represents lower alkyl, OH, NH2, NHR4 or NR5R6 wherein R4, R5 and R6 independently are lower alkyl or cyclo­alkyl and n is an integer of from 2 to 4, with the provision that when X is CH2, Y is OH or NH-(CH2)n-OH, and pharmacologically acceptable salts thereof are described. The compounds are useful as drugs for preventing and/or treating autoimmune diseases.

  式(I)中的新型取代吲哚并喹啉化合物，其中R1表示氢原子或选自卤素、较低烷基/烷氧基、羟基、三氟甲基、三氯甲基、三氟甲氧基等一种或多种相似或不同的取代基，在7到10位上取代；R2表示相似或不同的C1-C4烷基取代基；X为CO或CH2；Y为OH、NH2、NH-(CH2)n-R3，其中R3表示较低烷基、羟基、NH2、NHR4或NR5R6，其中R4、R5和R6独立地为较低烷基或环烷基，n为2到4的整数。当X为CH2时，Y为OH或NH-(CH2)n-OH。还描述了药理学上可接受的盐。这些化合物可用作预防和/或治疗自身免疫性疾病的药物。
• Alkyl substituted indoloquinoxalines
  申请人：Bergman Jan

  公开号：US20050288296A1

  公开（公告）日：2005-12-29

  Novel substituted indoloquinoxalines of formula (I wherein R 1 is hydrogen or represents one or more similar or different substituents in the positions 7 to 10 selected from the group halogen, lower alkyl/alkoxy, hydroxy, trifluoromethyl, trichloromethyl, trifluoromethoxy, R 2 represents similar or different C 1 -C 4 alkyl substituents, X is CO or CH 2 , Y is OH, NH 2 , NH—(CH 2 ) n —R 3 wherein R 3 represents lower alkyl, OH, NH 2 , NHR 4 or NR 5 R 6 wherein R 4 , R 5 and R 6 independently are lower alkyl or cyclo-alkyl and n is an integer of from 2 to 4, with the provision that when X is CH 2 , Y is OH or NH—(CH 2 ) n —OH, and pharmacologically acceptable salts thereof are described. The compounds are useful as drugs for preventing and/or treating autoimmune diseases.

  本发明涉及化学式（I）的新型取代吲哚并喹啉，其中R1为氢或在7到10位上选择自卤素、较低的烷基/烷氧基、羟基、三氟甲基、三氯甲基、三氟甲氧基等的一个或多个类似或不同的取代基；R2代表类似或不同的C1-C4烷基取代基；X为CO或CH2；Y为OH、NH2、NH—（CH2）n—R3，其中R3代表较低的烷基、羟基、NH2、NHR4或NR5R6，其中R4、R5和R6独立地为较低的烷基或环烷基，n为2到4的整数。但当X为CH2时，Y为OH或NH—（CH2）n—OH。所述化合物及其药学上可接受的盐可用作预防和/或治疗自身免疫性疾病的药物。
• Substituted indoloquinoxalines
  申请人：Lundblad, Leif

  公开号：EP0238459A1

  公开（公告）日：1987-09-23

  Substituted indoloquinoxalines of the general formula I in R₁ represents one or several, preferably 1 to 4, similar or different substituents in the positions 1-4 and/or 7-10, selected from halogen, preferably Br, lower alkyl/alkoxy group having not more than 4 carbon atoms, trifluoromethyl group, trichloromethyl group; X is a group -(CH₂)n-R₂ wherein R₂ represents a nitrogen containing basic residue such as NH₂, NHR₄ or NR₅R₆ wherein R₄, R₅ and R₆ independently are lower alkyl or cykloalkyl and n is an integer of from 1 to 4 and R₃ represents hydrogen, lower alkyl/cykloalkyl group having not more than 4 carbon atoms, and the physiologically acceptable addition products of the compounds with acids and halogen adducts, preferably adducts with iodine, iodine monochloride or iodine monobromide. Also methods for preparing said compounds by reacting a compound of the formula II with a reactive compound containing the residue -CHR₃X, or by rearranging a compound the formula III by heating are described. The novel indoloquinoxalines have antiviral effect and have effect against cancer.

  通式 I 的取代吲哚喹喔啉类 其中 R₁ 代表 1-4 位和/或 7-10 位上的一个或多个（优选 1 至 4 个）相似或不同的取代基，选自卤素（优选 Br）、具有不超过 4 个碳原子的低级烷基/烷氧基、三氟甲基、三氯甲基； X 是基团-(CH₂)n-R₂，其中 R₂ 代表含氮碱性残基，如 NH₂、NHR₄ 或 NR₅R₆，其中 R₄、R₅ 和 R₆ 独立地是低级烷基或环烷基，n 是 1 到 4 的整数，以及 R₃ 代表氢、具有不超过 4 个碳原子的低级烷基/环烷基、 以及这些化合物与酸和卤素加成物的生理学上可接受的加成产物，最好是与碘、一氯 化碘或一溴化碘的加成物。 制备上述化合物的方法还包括将式 II 的化合物 与含有残基 -CHR₃X 的活性化合物反应，或通过加热重排式 III 描述了通过加热重新排列式 III 的化合物的方法。 新型吲哚喹喔啉类化合物具有抗病毒和抗癌作用。
• Pharmaceutical formulation of B220 for topical treatment of herpes
  申请人：Vironova AB

  公开号：EP2489354A1

  公开（公告）日：2012-08-22

  A pharmaceutical composition for topical administration comprising 2,3-dimethyl-6-(N,N-dimethylaminoethyl)-6H-indolo-(2,3-b)quinoxaline (B-220) or a pharmaceutically acceptable salt thereof in a pharmaceutically acceptable carrier. The composition is useful for the treatment of herpes virus infections of the skin or mucous membranes in a mammal subject.

  一种用于局部用药的药物组合物，包含 2,3-二甲基-6-(N,N-二甲基氨基乙基)-6H-吲哚-(2,3-b)喹喔啉（B-220）或其药学上可接受的盐，以及药学上可接受的载体。该组合物可用于治疗哺乳动物皮肤或粘膜的疱疹病毒感染。