2-amino-7-bromo-5-(2-pyridyl)-3H-1,4-benzodiazepine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: 2-amino-7-bromo-5-(2-pyridyl)-3H-1,4-benzodiazepine
• 英文别名: 2-amino-7-bromo-5-(pyridin-2-yl)-3H-1,4-benzodiazepine；7-bromo-5-pyridin-2-yl-3H-1,4-benzodiazepin-2-amine
• 化学式: C₁₄H₁₁BrN₄
• 分子量: 315.172
• InChiKey: YCEZHTMDZAIVRB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-amino-7-bromo-5-(2-pyridyl)-3H-1,4-benzodiazepine 、 N,N-二异丙基乙胺 、 3-溴丙酮酸乙酯 、 乙醚 在 ice 作用下， 以 四氢呋喃 为溶剂， 反应 0.67h， 以49.5 g of N-ethyldiisopropylamine hydrobromide were obtained的产率得到diisopropylethylammonium bromide
  参考文献：
  名称：

  Hydroxymethylimidazodiazepines and their esters

  摘要：

  这项发明涉及一种通式为I的羟甲基咪唑二氮平及其酯类化合物。这些化合物可用作抗焦虑、抗惊厥、肌肉松弛和镇静催眠活性物质。

  公开号：

  US06174881B1
• 作为产物：
  描述：

  7-brom-1,3-dihydro-5-(2-pyridyl)-2H-1,4-benzodiazepin-2-thion 在 ammonium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 2-amino-7-bromo-5-(2-pyridyl)-3H-1,4-benzodiazepine
  参考文献：
  名称：

  Hydroxymethylimidazodiazepines and their esters

  摘要：

  这项发明涉及羟甲基咪唑二氮杂环己酮及其一般式I的酯类化合物。这些化合物可用作抗焦虑、抗癫痫、肌肉松弛和催眠-催眠活性物质。

  公开号：

  US06174881B1

文献信息

• HYDROBROMATE OF BENZODIAZEPINE DERIVATIVE, PREPARATION METHOD AND USE THEREOF
  申请人：Chengdu Brilliant Pharmaceutical Co., Ltd.

  公开号：EP3553059A1

  公开（公告）日：2019-10-16

  The present invention provides a hydrobromide of methyl 3-[(4s)-8-bromo-1-methyl-6-(2-pyridyl)-4H-imidazol[1,2-a][1,4]benzodiazepine-4-yl] propionate and its related crystal forms, preparation method and use thereof. The hydrobromide has excellent solubility (>100 mg/ml), which is significantly superior to other currently commercially available or developed salt products, and is especially suitable for the preparation of injections, has relatively good stability in various crystal forms, and has good practical value and market prospects.

  本发明提供了一种3-[(4s)-8-溴-1-甲基-6-(2-吡啶基)-4H-咪唑并[1,2-a][1,4]苯并二氮杂卓-4-基]丙酸甲酯氢溴酸盐及其相关晶型、制备方法和用途。该氢溴酸盐具有极佳的溶解度（>100 mg/ml），明显优于目前市售或已开发的其他盐类产品，尤其适合制备注射剂，在各种晶型中具有相对较好的稳定性，具有良好的实用价值和市场前景。
• [DE] HYDROXYMETHYL-IMIDAZODIAZEPINE UND DEREN ESTER<br/>[EN] HYDROXYMETHYLIMIDAZODIAZEPINES AND THEIR ESTERS<br/>[FR] HYDROXYMETHYLIMIDAZODIAZEPINES ET LEURS ESTERS
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：WO1996020941A1

  公开（公告）日：1996-07-11

  (DE) Die Erfindung betrifft Hydroxymethyl-imidazodiazepine und deren Ester der allgemeinen Formel (I). Diese Verbindungen können als anxiolytische und/oder antikonvulsive und/oder muskelrelaxierende und/oder sedativ-hypnotische Wirkstoffe angewendet werden, worin A zusammen mit den beiden mit $g(a) und $g(b) bezeichneten Kohlenstoffatomen einen der Reste (A1), (A2) oder (A3), R1 Wasserstoff oder nieder-Alkanoyl; R2 Phenyl, o-Halophenyl oder 2-Pyridyl; R3 Wasserstoff, nieder-Alkyl, Methylaminomethyl, Allylaminomethyl oder Diethylaminomethyl; R4 Halogen, CF3 oder Nitro; R5 Wasserstoff oder Halogen bedeuten.(EN) The invention pertains to hydroxymethylimidazodiazepines of general formula (I) and their esters. These compounds can be used as anxiolytic and/or anticonvulsive and/or muscle-relaxing and/or sedative hypnotic agents. In formula (I), A together with the two carbon atoms designated as $g(a) and $g(b) is one of the radicals (A1), (A2) or (A3); R1 is hydrogen or lower alkanoyl; R2 is phenyl, o-halophenyl or 2-pyridyl; R3 is hydrogen, lower alkyl, methylaminomethyl, allylaminomethyl or diethylaminomethyl; R4 is halogen, CF3 or nitro; R5 is hydrogen or halogen.(FR) L'invention concerne des hydroxyméthylimidazodiazépines de formule générale (I), ainsi que leurs esters. Ces composés peuvent être utilisés sous forme de principes actifs anxiolytiques et/ou anticonvulsifs et/ou myorelaxants et/ou sédatifs hypnotiques. Dans la formule (I), A représente, avec les deux atomes de carbone désignés par $g(a) et $g(b), un des radicaux (A1), (A2) ou (A3); R1 représente hydrogène ou alcanoyle inférieur; R2 représente phényle, o-halophényle ou 2-pyridyle; R3 représente hydrogène, alkyle inférieur, méthylaminométhyle, allylaminométhyle ou diéthylaminométhyle; R4 représente halogène, CF3 ou nitro; R5 représente hydrogène ou halogène.

  这项发明涉及一般公式(I)的羟甲基甲离子杂甲氧环胞嘧啶及其酯。这些化合物可以作为抗焦虑药、抗癫痫药、肌肉 relaxant 和莨菪 alkaloid 使用。在公式(I)中，A与两个标记为 $g(a) 和 $g(b) 的碳原子一起构成(A1)、(A2) 或 (A3)中的一个，R1是氢或低级的酸酐；R2是苯、o-卤苯或2-吡啶；R3是氢、低级烷基、甲基氨基甲基、 allyl氨基甲基或 diethyl氨基甲基；R4是卤素、CF3或硝基；R5是氢或卤素。
• Imidazodiazepine Anticonvulsant, KRM-II-81, Produces Novel, Non-diazepam-like Antiseizure Effects
  作者：Daniel E. Knutson、Jodi L. Smith、Xingjie Ping、Xiaoming Jin、Lalit K. Golani、Guanguan Li、V. V. N. Phani Babu Tiruveedhula、Farjana Rashid、Md Yeunus Mian、Rajwana Jahan、Dishary Sharmin、Rok Cerne、James M. Cook、Jeffrey M. Witkin

  DOI：10.1021/acschemneuro.0c00295

  日期：2020.9.2

  The need for improved medications for the treatment of epilepsy and chronic pain is essential. Epileptic patients typically take multiple antiseizure drugs without complete seizure freedom, and chronic pain is not fully managed with current medications. A positive allosteric modulator (PAM) of alpha 2/3-containing GABA(A) receptors (5-(8-ethynyl-6-(pyridin-2-yl)-4H-benzo[f]imidazole[1,5-alpha][1,4]diazepin-3-yl) oxazole or KRM-II-81 (8) is a lead compound in a series of imidazodiazepines. We previously reported that KRM-II-81 produces broad-based anticonvulsant and antinociceptive efficacy in rodent models and provides a wider margin over motoric side effects than that of other GABA(A) receptor PAMs. The present series of experiments was designed to fill key missing gaps in prior preclinical studies assessing whether KRM-II-81 could be further differentiated from nonselective GABA(A) receptor PAMs using the anticonvulsant diazepam (DZP) as a comparator. In multiple chemical seizure provocation models in mice, KRM-II-81 was either equally or more efficacious than DZP. Most strikingly, KRM-II-81 but not DZP blocked the development of seizure sensitivity to the chemoconvulsants cocaine and pentylenetetrazol in seizure kindling models. These and predecessor data have placed KRM-II-81 into consideration for clinical development requiring the manufacture of kilogram amounts of good manufacturing practice material. We describe here a novel synthetic route amenable to kilogram quantity production. The new biological and chemical data provide key steps forward in the development of KRM-II-81 (8) as an improved treatment option for patients suffering from epilepsy.
• HYDROXYMETHYL-IMIDAZODIAZEPINE UND DEREN ESTER
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0801651B1

  公开（公告）日：2001-07-11
• 8-BROMO-1-METHYL-6-(2-PYRIDINYL)-4H-IMIDAZO[1,2-A][1,4]BENZODIAZEPINE-4-PROPANOIC ACID METHYL ESTER (REMIMAZOLAM, CNS 7056) HYDROBROMIDE (1:1) SALT FOR INJECTION FOR SEDATION AND ANESTHESIA
  申请人：Chengdu Brilliant Pharmaceutical Co., Ltd.

  公开号：EP3553059B1

  公开（公告）日：2021-10-13