5,11-Dioxo-10,11-dihydro-5H-pyrrolo<2,1-c><1,4>benzodiazepine | 76447-29-5

• 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: 5,11-Dioxo-10,11-dihydro-5H-pyrrolo<2,1-c><1,4>benzodiazepine
• 英文别名: 5,11-Dioxo-10,11-dihydro-5H-pyrrolo<2,1-c>(1,4)benzodiazepine；5H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11(10H)-dione；5H-pyrrolo[2,1-c][1,4]benzodiazepine-6,11-dione
• CAS: 76447-29-5
• 化学式: C₁₂H₈N₂O₂
• 分子量: 212.208
• InChiKey: VUMOEZLRLXJCIQ-UHFFFAOYSA-N

物化性质

• 沸点：
  241.6±23.0 °C(Predicted)
• 密度：
  1.41±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  51.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5,11-Dioxo-10,11-dihydro-5H-pyrrolo<2,1-c><1,4>benzodiazepine 在 氨 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以95%的产率得到N-(2-氨基甲酰基苯基)-1H-吡咯-2-甲酰胺
  参考文献：
  名称：

  芳族吡咯并[2,1- c ] [1,4]苯并二氮杂的简便途径及其反应性研究

  摘要：

  2-羟基吡咯并[2,1- c ^ ] [1,4]苯并二氮杂类中在回流的亚硫酰氯为11个氯吡咯芳香烃[2,1- c ^ ] [1,4]高收率苯二氮。该芳族体系对亲核试剂具有双反应性，从而导致重排产物，如亚氨基苯并恶嗪和喹唑啉。

  DOI：

  10.1016/s0040-4039(01)00957-1
• 作为产物：
  描述：

  2-吡咯甲酸甲酯 在 palladium on activated charcoal 盐酸 、 氢气 、 sodium hydride 作用下， 反应 24.0h， 生成 5,11-Dioxo-10,11-dihydro-5H-pyrrolo<2,1-c><1,4>benzodiazepine
  参考文献：
  名称：

  Singh, Rajeshwar; Jain, Padam C.; Anand, Nitya, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1982, vol. 21, # 3, p. 225 - 227

  摘要：

  DOI：

文献信息

• CHELATE NANOEMULSION FOR MRI
  申请人：Port Marc

  公开号：US20130309176A1

  公开（公告）日：2013-11-21

  The present invention relates to an oil-in-water nanoemulsion composition for MRI, comprising: an aqueous phase, representing 70% to 90% by weight of the composition, advantageously 75% to 85% and more advantageously from 78% to 82% a lipid phase comprising an oil, representing 9.5% to 29.5% by weight of the composition, advantageously 14% to 25% and more advantageously 17% to 21%, a surfactant at the interface between the aqueous and lipid phases, the surfactant comprising at least one amphiphilic paramagnetic metal chelate and optionally an amphiphilic lipid; the total content of surfactant by weight relative to the oil being between 4% and 10% and advantageously between 5% and 8%; the total content of surfactant by weight relative to the composition being between 0.35% and 2.95% and advantageously between 0.5% and 2%; the oil comprising at least 70%, advantageously at least 80%, advantageously at least 95% by weight and especially at least 97% of saturated C6-C18, advantageously C6-C14 and more advantageously C6-C10 fatty acids.

  本发明涉及一种用于磁共振成像的油包水纳米乳液组合物，包括： 水相，表示组合物重量的70%至90%，优选75%至85%，更优选78%至82%； 脂相包括一种油，表示组合物重量的9.5%至29.5%，优选14%至25%，更优选17%至21%； 表面活性剂位于水相和脂相之间的界面上，表面活性剂包括至少一种两性磁性金属螯合物和可选的两性脂质； 相对于油的重量，表面活性剂的总含量在4%至10%之间，优选在5%至8%之间； 相对于组合物的重量，表面活性剂的总含量在0.35%至2.95%之间，优选在0.5%至2%之间； 油包括至少70%，优选至少80%，优选至少95%的饱和C6-C18，优选C6-C14，更优选C6-C10脂肪酸。
• Vectorised Magnetic Emulsion
  申请人：GUERBET

  公开号：US20150320889A1

  公开（公告）日：2015-11-12

  An oil-in-water nanoemulsion composition for MRI, comprising an aqueous phase, a lipid phase as nanodroplets comprising an oil and magnetic particles based on an iron compound and covered with one or several C8-C22 fatty acids, and a mixture of surfactants at the interface between the aqueous and lipid phases, the mixture of surfactants comprising at least one amphiphilic lipid and at least one amphiphilic targeting ligand.

  一种用于磁共振成像的油包水纳米乳液组合物，包括水相、作为纳滴的脂肪相，其中包括一种油和基于铁化合物的磁性粒子，并且被一种或几种C8-C22脂肪酸覆盖，以及存在于水相和脂肪相之间界面的表面活性剂混合物，该表面活性剂混合物包括至少一种两性脂质和至少一种两性靶向配体。
• [EN] 11-HYDROXY-5H-PYRROLO[2,1-C][1,4]BENZODIAZEPIN-5-ONE DERIVATIVES AS KEY INTERMEDIATES FOR THE PREPARATION OF C2 SUBSTITUTED PYRROLOBENZODIAZEPINES<br/>[FR] DERIVES DE 11-HYDROXY-5H-PYRROLO[2,1-C][1,4] BENZODIAZEPINE-5-ONE EN TANT QU'INTERMEDIAIRES CLES POUR LA PREPARATION DE PYRROLOBENZODIAZEPINES SUBSTITUEES C2
  申请人：SPIROGEN LTD

  公开号：WO2005085251A1

  公开（公告）日：2005-09-15

  The present inventors have developed a key intermediate for the production of C2 substituted PBDs, which has a leaving group at the C2 position, a carbamate protecting group at the N10 position and a protected hydroxy group at the C11 position. In a first aspect, the present invention comprises a compound with a the formula (I), wherein : R10 is a carbamate-based nitrogen protecting group; R11 is an oxygen protecting group; and R2 is a labile leaving group. In a further aspect, the present invention comprises a method of synthesising a compound of formula (III), or a solvate thereof, from a compound of formula (I) as defined in the first aspect, R16 is either O-R11, wherein R11 is as defined in the first aspect, or OH, or R10 and R16 together form a double bond between N10 and C11; and R15 is R. The other substituents are defined in the claims. Further aspects of the present invention relate to compounds of formula (III) (including solvates thereof when R10 and R16 form a double bond between N10 and C11, and pharmaceutical salts thereof), pharmaceutical compositions comprising these, and their use in the manufacture of a medicament for the treatment of a proliferative disease.

  本发明人已经开发出一种用于生产C2取代PBDs的关键中间体，该中间体在C2位置具有一个离去基团，在N10位置具有一个氨基甲酸酯保护基团，在C11位置具有一个受保护的羟基。根据第一方面，本发明涉及一种具有以下式（I）的化合物，其中：R10是一种基于氨基甲酸酯的氮保护基团；R11是一种氧保护基团；R2是一种不稳定的离去基团。根据进一步方面，本发明涉及一种从根据第一方面中定义的式（I）的化合物合成式（III）的方法，或者其溶剂化物，其中R16是O-R11，其中R11如第一方面中定义，或OH，或者R10和R16一起形成N10和C11之间的双键；R15是R。其他取代基在权利要求中定义。本发明的进一步方面涉及式（III）的化合物（包括当R10和R16形成N10和C11之间的双键时的溶剂化物，以及其药用盐），包括这些化合物的药用组合物，以及它们在制造用于治疗增殖性疾病的药物的药物的用途。
• Pyrrolo-benzodiazepines, method of preparation and method of use
  申请人：American Cyanamid Company

  公开号：US03947408A1

  公开（公告）日：1976-03-30

  Derivatives of 1,2,3,5,10,11a-hexahydro-11H-pyrrolo[2,1-c][1,4]benzodiazepin-11-one in the form of their racemic mixtures, optical isomers and salts, their method of preparation and method of use are described. The compounds are useful in treating anxiety in warm-blooded animals.

  本文描述了1,2,3,5,10,11a-hexahydro-11H-pyrrolo[2,1-c][1,4]苯并二氮平-11-酮的衍生物，包括它们的外消旋混合物，光学异构体和盐，以及它们的制备方法和使用方法。这些化合物可用于治疗温血动物的焦虑症。
• 11-Hydroxy-5h-pyrrolo[2,1-c][1,4] benzodiazepin-5-one derivatives as key intermediates for the preparation of c2 substituted pyrrolobenzodiazepines
  申请人：Howard Wilson Philip

  公开号：US20070173497A1

  公开（公告）日：2007-07-26

  The present inventors have developed a key intermediate for the production of C2 substituted PBDs, which has a leaving group at the C2 position, a carbamate protecting group at the N10 position and a protected hydroxy group at the C11 position. In a first aspect, the present invention comprises a compound with a the formula (I), wherein: R 10 is a carbamate-based nitrogen protecting group; R 11 is an oxygen protecting group; and R 2 is a labile leaving group. In a further aspect, the present invention comprises a method of synthesising a compound of formula (III), or a solvate thereof, from a compound of formula (I) as defined in the first aspect, R 16 is either O—R11, wherein R 11 is as defined in the first aspect, or OH, or R 10 and R 16 together form a double bond between N10 and C11; and R 15 is R. The other substituents are defined in the claims. Further aspects of the present invention relate to compounds of formula (III) (including solvates thereof when R 10 and R 16 form a double bond between N10 and C11, and pharmaceutical salts thereof), pharmaceutical compositions comprising these, and their use in the manufacture of a medicament for the treatment of a proliferative disease.

  本发明的发明人开发了一种用于生产C2取代PBD的关键中间体，该中间体在C2位置具有离去基团，在N10位置具有氨基甲酸酯保护基团，在C11位置具有保护羟基。在第一个方面，本发明涉及一种具有式(I)的化合物，其中：R10是基于氨基甲酸酯的氮保护基团；R11是氧保护基团；R2是易离基团。在进一步方面，本发明涉及一种从式(I)的化合物中合成式(III)的化合物或其溶剂化物的方法，其中R16是O-R11，其中R11如第一个方面中所定义，或者是OH，或者是R10和R16共同形成N10和C11之间的双键；R15是R。其他取代基在权利要求中定义。本发明的其他方面涉及式(III)的化合物（包括当R10和R16形成N10和C11之间的双键及其药物盐时的溶剂化物），包含这些的药物组合物，并将其用于制造用于治疗增生性疾病的药物。