Ethyl 5-bromo-2,7-dimethyl-8-[(2-methylimidazol-1-yl)methyl]-1,3-dihydropyrrolo[3,2-f][1,3]benzoxazine-9-carboxylate | 958450-04-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: Ethyl 5-bromo-2,7-dimethyl-8-[(2-methylimidazol-1-yl)methyl]-1,3-dihydropyrrolo[3,2-f][1,3]benzoxazine-9-carboxylate
• CAS: 958450-04-9
• 化学式: C₂₀H₂₃BrN₄O₃
• 分子量: 447.332
• InChiKey: ZLQZLLLICJMVKM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  61.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  糠醛 、 聚合甲醛 、 正戊醛 、 Ethyl 6-bromo-5-hydroxy-1-methyl-2-[(2-methylimidazol-1-yl)methyl]indole-3-carboxylate 、 Ethyl 6-bromo-5-hydroxy-2-[[2-hydroxyethyl(methyl)amino]methyl]-1-methylindole-3-carboxylate 、 6-Bromo-5-hydroxy-1-methyl-2-[(pyridin-4-ylamino)methyl]-3-indolecarboxylic acid ethyl ester 、 ethyl-6-bromo-2-((dimethylamino)methyl)-5-hydroxy-1-phenyl-1H-indole-3-carboxylate 、 、 Ethyl 5-hydroxy-2-[(4-methylpiperazino)methyl]-1-phenyl-1H-indole-3-carboxylate 、 Ethyl 5-hydroxy-1-methyl-6-(3-pyridyl)-2-(1-pyrrolidinylmethyl)-1H-indole-3-carboxylate 、 、 、 、 、 、 、 、 ethyl 1-benzyl-6-bromo-5-hydroxy-2-[(2-methylpiperidin-1-yl)methyl]-1H-indole-3-carboxylate 、 ethyl 1-benzyl-6-bromo-5-hydroxy-2-[(4-methylpiperidin-1-yl)methyl]-1H-indole-3-carboxylate 、 ethyl 1-benzyl-6-bromo-5-hydroxy-2-(piperidin-1-ylmethyl)-1H-indole-3-carboxylate 、 ethyl 6-bromo-1-cyclohexyl-5-hydroxy-2-[(4-phenylpiperazin-1-yl)methyl]-1H-indole-3-carboxylate 、 苯甲醛 、 6-Bromo-5-hydroxy-1-methyl-2-phenylaminomethyl-1H-indole-3-carboxylic acid ethyl ester 、 甲胺 、 苄胺 以 1,4-二氧六环 为溶剂， 反应 48.0h， 生成 Ethyl 5-bromo-2,7-dimethyl-8-[(2-methylimidazol-1-yl)methyl]-1,3-dihydropyrrolo[3,2-f][1,3]benzoxazine-9-carboxylate 、 Ethyl 5-bromo-2,7-dimethyl-8-(phenoxymethyl)-1,3-dihydropyrrolo[3,2-f][1,3]benzoxazine-9-carboxylate 、 ethyl 3,7-dimethyl-6-(phenylsulfonylmethyl)-9-cyano-1,2,3,7-tetrahydropyrrolo[3,2-f][1,3]benzoxazine-5-carboxylate 、 Ethyl 5-bromo-8-[[2-hydroxyethyl(methyl)amino]methyl]-2,7-dimethyl-1,3-dihydropyrrolo[3,2-f][1,3]benzoxazine-9-carboxylate 、 Ethyl 2,7-dimethyl-8-(methylaminomethyl)-5-pyridin-3-yl-1,3-dihydropyrrolo[3,2-f][1,3]benzoxazine-9-carboxylate 、 ethyl 9-bromo-3,7-dimethyl-6-((phenylamino)methyl)-1,2,3,7-tetrahydropyrrolo[3,2-f][1,3]benzoxazine-5-carboxylate 、 ethyl 9-bromo-3,7-dimethyl-6-((pyridin-4-yl)methyl)-1,2,3,7-tetrahydropyrrolo[3,2-f][1,3]benzoxazine-5-carboxylate 、 ethyl 9-bromo-6-((dimethylamino)methyl)-3-methyl-7-phenyl-1,2,3,7-tetrahydropyrrolo[3,2-f][1,3]benzoxazine-5-carboxylate 、 Ethyl 5-bromo-2,7-dimethyl-8-[(4-methylanilino)methyl]-1,3-dihydropyrrolo[3,2-f][1,3]benzoxazine-9-carboxylate 、 Ethyl 8-(anilinomethyl)-5-bromo-3-(furan-2-yl)-2,7-dimethyl-1,3-dihydropyrrolo[3,2-f][1,3]benzoxazine-9-carboxylate 、 Ethyl 2-methyl-8-[(4-methylpiperazin-1-yl)methyl]-7-phenyl-1,3-dihydropyrrolo[3,2-f][1,3]benzoxazine-9-carboxylate 、 Ethyl 5-bromo-2,7-dimethyl-3-phenyl-8-(phenylsulfanylmethyl)-1,3-dihydropyrrolo[3,2-f][1,3]benzoxazine-9-carboxylate 、 Ethyl 2-benzyl-5-bromo-7-methyl-8-(phenylsulfanylmethyl)-1,3-dihydropyrrolo[3,2-f][1,3]benzoxazine-9-carboxylate 、 Ethyl 2,7-dimethyl-5-(pyridin-3-YL)-8-[(pyrrolidin-1-YL)methyl]-1H,2H,3H,7H-[1,3]oxazino[5,6-E]indole-9-carboxylate 、 ethyl 3,7-dimethyl-9-(pyridin-4-yl)-6-(phenylsulfonylmethyl)-1,2,3,7-tetrahydropyrrolo[3,2-f][1,3]benzoxazine-5-carboxylate 、 Ethyl 5-bromo-8-[(2-cyano-5-methylphenyl)sulfanylmethyl]-2,7-dimethyl-1,3-dihydropyrrolo[3,2-f][1,3]benzoxazine-9-carboxylate 、 Benzyl 5-bromo-2,7-dimethyl-8-(morpholin-4-ylmethyl)-1,3-dihydropyrrolo[3,2-f][1,3]benzoxazine-9-carboxylate 、 Ethyl 5-bromo-8-[[4-(cyanomethyl)piperazin-1-yl]methyl]-2,7-dimethyl-1,3-dihydropyrrolo[3,2-f][1,3]benzoxazine-9-carboxylate 、 Cyclohexyl 8-(anilinomethyl)-5-bromo-2,7-dimethyl-1,3-dihydropyrrolo[3,2-f][1,3]benzoxazine-9-carboxylate 、 Ethyl 5-bromo-8-[[4-(2-hydroxyethyl)piperazin-1-yl]methyl]-2,7-dimethyl-1,3-dihydropyrrolo[3,2-f][1,3]benzoxazine-9-carboxylate 、 Ethyl 7-benzyl-5-bromo-2-methyl-8-[(2-methylpiperidin-1-yl)methyl]-1,3-dihydropyrrolo[3,2-f][1,3]benzoxazine-9-carboxylate 、 Ethyl 7-benzyl-5-bromo-2-methyl-8-[(4-methylpiperidin-1-yl)methyl]-1,3-dihydropyrrolo[3,2-f][1,3]benzoxazine-9-carboxylate 、 Ethyl 7-benzyl-5-bromo-2-methyl-8-(piperidin-1-ylmethyl)-1,3-dihydropyrrolo[3,2-f][1,3]benzoxazine-9-carboxylate 、 ethyl 7-benzyl-9-bromo-3-methyl-6-((1-methylpiperazin-4-yl)methyl)-1,2,3,7-tetrahydropyrrolo[3,2-f][1,3]benzoxazine-5-carboxylate 、 Ethyl 5-bromo-7-cyclohexyl-2-methyl-8-[(4-phenylpiperazin-1-yl)methyl]-1,3-dihydropyrrolo[3,2-f][1,3]benzoxazine-9-carboxylate
  参考文献：
  名称：

  EP2036889

  摘要：

  公开号：

文献信息

• Substituted Indoles and a Method for the Production and Use Thereof
  申请人：Ivashchenko Andrey Alexandrovich

  公开号：US20110160197A1

  公开（公告）日：2011-06-30

  The invention relates to novel substituted indoles, to the use thereof in the form of pharmacological composition substances and to use of said composition for producing medicinal preparations used for preventing and treating viral diseases, in particular caused by viruses of infectious hepatitis (HCV, HBV), human immune deficiency (HIV), atypical pneumonia (SARS) and bird flu. The invention proposes novel substituted indoles of general formula (1) or the racemates or the optical isomers or the pharmaceutically acceptable salts and/or hydrates thereof, wherein R 1 , R 1 4 and R 2 4 independently of each other are an aminogroup substituent selected for hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl or optionally substituted heterocyclyl, or R 1 4 and R 2 4 together with a nitrogen atom, with which they are bound, form through R 1 4 and R 2 4 optionally substituted azaheterocyclyl or guanidyl; R 2 is analkyl substituent selected from hydrogen, an optionally substituted mercaptogroup, optionally substituted aminogroup and optionally substituted hydroxyl; R 3 is lower alkyl, R 5 is an hydrogen atom or R 5 together with an oxygen atom with which it is linked or R 2 4 together with a nitrogen atom with which it is linked close, via R 5 and R 2 4 an oxazine cycle; R 6 is a cyclic system substituent selected for hydrogen, a halogen atom, cyanogroup, optionally substituted aryl or substituted heterocyclyl.
• US8329689B2
  申请人：——

  公开号：US8329689B2

  公开（公告）日：2012-12-11
• [EN] SUBSTITUTED INDOLES AND A METHOD FOR THE PRODUCTION AND USE THEREOF<br/>[FR] INDOLES SUBSTITUÉS ET PROCÉDÉ DE PRODUCTION ET D'UTILISATION DE CEUX-CI
  申请人：ALLA CHEM LLC

  公开号：WO2007136300A2

  公开（公告）日：2007-11-29

  [EN] The invention relates to novel substituted indoles, to the use thereof in the form of pharmacological composition substances and to use of said composition for producing medicinal preparations used for preventing and treating viral diseases, in particular caused by viruses of infectious hepatitis (HCV, HBV), human immune deficiency (HIV), atypical pneumonia (SARS) and bird flu. The invention proposes novel substituted indoles of general formula (1) or the racemates or the optical isomers or the pharmaceutically acceptable salts and/or hydrates thereof, wherein R¹, R₁ ⁴
  [FR] La présente invention concerne de nouveaux indoles substitués, leur utilisation comme substances de compositions pharmaceutiques et l'utilisation de ces compositions pour produire des préparations médicinales destinée à la prévention et au traitement de maladies virales, en particulier causées par les virus d'hépatites infectieuses (virus de l'hépatite C, virus de l'hépatite B), le virus de l'immunodéficience humaine (VIH), la pneumonie atypique (SRAS) et la grippe aviaire. Cette invention concerne de nouveaux indoles substitués représentés par la formule (I) ou des racémates, des isomères optiques, des sels et/ou hydrates pharmaceutiquementacceptables de ceux-ci. Dans cette formule, R¹, R₁ ⁴
• [EN] ACTIVE SUBSTANCES, PHARMACEUTICAL COMPOSITION AND A METHOD FOR THE PRODUCTION AND USE THEREOF<br/>[FR] SUBSTANCES ACTIVES, COMPOSITION PHARMACEUTIQUE ET PROCÉDÉ DE FABRICATION ET D'UTILISATIONS CORRESPONDANTS
  申请人：ALLA CHEM LLC

  公开号：WO2007136302A2

  公开（公告）日：2007-11-29

  (EN) The invention relates to novel substituted indoles, to the use thereof in the form of pharmacological composition substances for producing medicinal preparations used for preventing and treating influenza and acute respiratory diseases. The substituted indoles of general formula (1) or the racemates or the optical isomers or the pharmaceutically acceptable salts and/or hydrates thereof, are proposed for the use thereof in the form of active substances of pharmaceutical compositions exhibiting antiviral activity against influenza and acute respiratory diseases, wherein R1, R14 and R24 independently of each other are an aminogroup substituent selected for hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl or optionally substituted heterocyclyl, or R14 and R24 together with a nitrogen atom,with which they are bound, form through R14 and R24 optionally substituted azaheterocyclyl or guanidyl; R 2 is an alkyl substituent selected from hydrogen, an optionally substituted mercaptogroup, optionally substituted aminogroup and optionally substituted hydroxyl; R 3 is lower alkyl, R 5 is an hydrogen atom or R 5 together with an oxygen atom with which it is linked or R24 together with a nitrogen atom with which it is linked close, via R 5 and R24 an oxazine cycle; R 6 is a cyclic system substituent selected for hydrogen, a halogen atom, cyanogroup, optionally substituted aryl or substituted heterocyclyl.(FR) L'invention concerne de nouveaux indoles substitués et leur utilisation en tant que substances actives de compositions pharmaceutiques ainsi que l'utilisation de ces dernières pour obtenir des préparations médicamenteuses utilisées dans la prévention et le traitement de la grippe et de maladies respiratoires aiguës. Elle propose en tant que substances actives de compositions pharmaceutiques possédant un action contre le virus de la grippe ou de maladies respiratoires aiguës des indoles substitués ayant la formule générale (1) ou leurs racémates, ou leurs isomères optiques, ou leurs sels et/ou hydrates pharmaceutiquement acceptables (Formule 1) dans laquelle R1, R14 et R24 sont indépendamment un substitutif d'un groupe aminé sélectionné parmi l'hydrogène, un alkyle éventuellement substitué, un cycloalkyle éventuellement substitué, un aryle éventuellement substitué ou un hétérocyclyle éventuellement substitué, ou R1, R14 et R24, conjointement avec l'atome d'azote auquel ils sont liés, forment via R14 et R24 un azahétérocyclyle ou un guanidyle éventuellement substitué; R2 se présente comme un substitutif alkylé, sélectionné parmi l'hydrogène, d'un groupe mercapto éventuellement substitué, un groupe aminé éventuellement substitué, un hydroxyle éventuellement substitué; R3 se présente comme un alkyle inférieur; R5 se présente comme un atome d'hydrogène ou R5, conjointement avec l'atome d'oxygène auquel il lié, et R24, conjointement avec l'atome d'azote auquel il est lié, referment le noyau oxazine; R6 se présente comme un substitutif du système cyclique sélectionné parmi l'hydrogène, un atome halogène, un groupe cyano, un aryle éventuellement substitué ou un hétérocyclyle éventuellement substitué.(RU) Настоящее изобретение относится к новым замещенным индолам и их применению в качестве активных субстанций фармацевтических композиций и использованию последних для получения лекарственных препаратов, применяемых для профилактики и лечения гриппа и острых респираторных заболеваний. Предложены в качестве активных субстанций фармацевтических композиций, обладающих активностью против вирусов гриппа и острых респираторных заболеваний, замещенные индолы общей формулы 1 или их рацематы, или их оптические изомеры, или их фармацевтически приемлемые соли и/или гидраты. (где: R1, R14 и R24 независимо друг от друга представляют собой заместитель аминогруппы, выбранный из водорода, необязательно замещенного алкила, необязательно замещенного циклоалкила, необязательно замещенного арила или необязательно замещенного гетероциклила, или R1 и R24 , вместе с атомом азота с которым они связаны, образуют через R14 и R24 необязательно замещенный азагетероциклил или гуанидил; R2 представляет собой заместитель алкильный, выбранный из водорода, необязательно замещенной меркапто группы, необязательно замещенной амино группы, необязательно замещенного гидроксила; R3 представляет собой низший алкил; R5 представляет собой атом водорода или R5, вместе с атомом кислорода, с которым он связан, и R24, вместе с атомом азота, с которым он связан, замыкают через R5 и R24 оксазиновый цикл; R представляет собой заместитель циклической системы выбранный из водорода, атома галогена, циано группы, необязательно замещенного арила или необязательно замещенного гетероциклила
• EP2036889
  申请人：——

  公开号：——

  公开（公告）日：——