10-[(2-methyl-2'-trifluoromethyl-[1,1'-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid | 473260-51-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 10-[(2-methyl-2'-trifluoromethyl-[1,1'-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid
• 英文别名: 10-(2-methyl-2′-trifluoromethylbiphenyl-4-carbonyl)-10,11-dihydro-5H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-3-carboxylic acid；10-(2-methyl-2'-trifluoromethyl-biphenyl-4-carbonyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid；10-[(2-Methyl-2'-trifluoromethyl-[1,1'-biphenyl]4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo [2,1-c][1,4]benzodiazepine-3-carboxylic acid；5-[3-methyl-4-[2-(trifluoromethyl)phenyl]benzoyl]-6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepine-9-carboxylic acid
• CAS: 473260-51-4
• 化学式: C₂₈H₂₁F₃N₂O₃
• 分子量: 490.482
• InChiKey: KGFYJHKUAZGBQF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  36
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  62.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  10-[(2-methyl-2'-trifluoromethyl-[1,1'-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid 在 sodium hydride 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 氘代四氢呋喃 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 1.0h， 生成 10-(2-methyl-2′-trifluoromethylbiphenyl-4-carbonyl)-10,11-dihydro-5H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-3-carboxylic acid (2-fluoroethyl)methyl amide
  参考文献：
  名称：

  新型非肽18 F标签放射性示踪剂的开发，用于正电子发射断层摄影术对催产素受体的体内成像。

  摘要：

  为了使用正电子发射断层扫描（PET）对活体大脑中的催产素受体（OTR）进行成像和定量，我们开发了一种18 F标记的小分子放射性示踪剂，并研究了其在小鼠和猪中的体内药代动力学。[ 18 F] 6b（K D = 12.3 nM）经两步法使用微波系统进行放射性标记，放射化学收率为26.9±4.7％。器官分布和小动物PET研究均显示有限的[ 18 F] 6b脑摄取在老鼠身上（在pi的30分钟时，SUV平均为0.04）。此外，在垂体中观察到显着的放射性吸收（在pi 30分钟时SUV为0.7）。在对一只仔猪进行的动态PET研究中，我们检测到嗅球中[ 18 F] 6b的摄取较高（在pi 30分钟时SUV为0.34），而整个大脑的摄取较低。猪脑切片的体外放射自显影研究表明[ 18 F] 6b与几种脱靶受体的相互作用。

  DOI：

  10.1021/acs.jmedchem.5b01080
• 作为产物：
  描述：

  4-溴-3-甲基苯甲酸甲酯 在 四(三苯基膦)钯 、 sodium carbonate 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 30.0h， 生成 10-[(2-methyl-2'-trifluoromethyl-[1,1'-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid
  参考文献：
  名称：

  新型非肽18 F标签放射性示踪剂的开发，用于正电子发射断层摄影术对催产素受体的体内成像。

  摘要：

  为了使用正电子发射断层扫描（PET）对活体大脑中的催产素受体（OTR）进行成像和定量，我们开发了一种18 F标记的小分子放射性示踪剂，并研究了其在小鼠和猪中的体内药代动力学。[ 18 F] 6b（K D = 12.3 nM）经两步法使用微波系统进行放射性标记，放射化学收率为26.9±4.7％。器官分布和小动物PET研究均显示有限的[ 18 F] 6b脑摄取在老鼠身上（在pi的30分钟时，SUV平均为0.04）。此外，在垂体中观察到显着的放射性吸收（在pi 30分钟时SUV为0.7）。在对一只仔猪进行的动态PET研究中，我们检测到嗅球中[ 18 F] 6b的摄取较高（在pi 30分钟时SUV为0.34），而整个大脑的摄取较低。猪脑切片的体外放射自显影研究表明[ 18 F] 6b与几种脱靶受体的相互作用。

  DOI：

  10.1021/acs.jmedchem.5b01080

文献信息

• Novel tricyclic diazepines tocolytic oxytocin receptor antagonists
  申请人：Wyeth

  公开号：US20030008863A1

  公开（公告）日：2003-01-09

  This invention provides novel tricyclic diazepine compounds as well as methods and pharmaceutical compositions utilizing these compounds for the treatment and/or prevention and/or suppression of disorders which may be remedied or alleviated by oxytocin antagonist activity, including treatment of preterm labor, dysmenorrhea, endometritis, and for suppressing labor prior to caesarean delivery. These compounds are also useful in enhancing fertility rates, enhancing survival rates and synchronizing estrus in farm animals; and may be useful in the prevention and treatment of disfunctions of the oxytocin system in the central nervous system including obsessive compulsive disorder (OCD) and neuropsychiatric disorders.

  这项发明提供了新颖的三环二氮杂平烯类化合物，以及利用这些化合物进行治疗和/或预防和/或抑制可能通过催产素拮抗剂活性得到缓解或减轻的疾病的方法和药物组合物，包括早产、经痛、子宫内膜炎的治疗，以及在剖宫产前抑制分娩。这些化合物还可用于提高农场动物的生育率、生存率和同步发情；并且可能在预防和治疗中枢神经系统中催产素系统功能障碍，包括强迫症（OCD）和神经精神障碍方面有用。
• Novel tricyclic pyridyl carboxamides and derivatives thereof tocolytic oxytocin receptor antagonists
  申请人：Wyeth

  公开号：US20030055047A1

  公开（公告）日：2003-03-20

  This invention provides novel substituted tricyclic pyridyl carboxamides which act as oxytocin receptor competitive antagonists, as well as methods of their manufacture, pharmaceutical compositions and methods of their use in treatment, inhibition, suppression or prevention of preterm labor, dysmenorrhea, endometritis, suppression of labor at term prior to caesarean delivery, and to facilitate antinatal transport to a medical facility. These compounds are also useful in enhancing fertility rates, enhancing survival rates and synchronizing estrus in farm animals; and may be useful in the prevention and treatment of disfunctions of the oxytocin system in the central nervous system including obsessive compulsive disorder (OCD) and neuropsychiatric disorders.

  这项发明提供了新型的取代三环吡啶基羧酰胺，其作为催产素受体竞争性拮抗剂，以及其制备方法、药物组合物和在治疗、抑制、压制或预防早产、痛经、子宫内膜炎、术前剖宫产前期压制分娩以及促进孕产妇前往医疗机构的使用方法。这些化合物还可用于提高农场动物的生育率、生存率和同步发情；并且可能有助于预防和治疗中枢神经系统中催产素系统功能障碍，包括强迫症（OCD）和神经精神障碍。
• Novel tricyclic hydroxy carboxamides and derivatives thereof tocolytic oxytocin receptor antagonists
  申请人：Wyeth

  公开号：US20030018026A1

  公开（公告）日：2003-01-23

  This invention provides novel substituted tricyclic carboxamides which act as oxytocin receptor competitive antagonists, as well as methods of their manufacture, pharmaceutical compositions and methods of their use in treatment, inhibition, suppression or prevention of preterm labor, dysmenorrhea and endometritis, suppression of labor at term prior to caesarean delivery, and to facilitate antinatal transport to a medical facility. These compounds are also useful in enhancing fertility rates, enhancing survival rates and synchronizing estrus in farm animals; and may be useful in the prevention and treatment of disfunctions of the oxytocin system in the central nervous system including obsessive compulsive disorder (OCD) and neuropsychiatric disorders.

  该发明提供了新颖的替代三环羧酰胺，其作为催产素受体竞争性拮抗剂，以及其制备方法、药物组合物和在治疗、抑制、压制或预防早产、痛经和子宫内膜炎、在剖宫产前抑制分娩以及促进孕妇转运至医疗机构的使用方法。这些化合物还可用于提高农场动物的生育率、提高存活率和同步动物的发情期；并且可能在预防和治疗中枢神经系统中催产素系统功能障碍，包括强迫症（OCD）和神经精神障碍方面具有用处。
• Tricyclic hydroxy carboxamides and derivatives thereof tocolytic oxytocin receptor antagonists
  申请人：Failli Amedeo Arturo

  公开号：US06900200B2

  公开（公告）日：2005-05-31

  This invention provides novel substituted tricyclic carboxamides which act as oxytocin receptor competitive antagonists, as well as methods of their manufacture, pharmaceutical compositions and methods of their use in treatment, inhibition, suppression or prevention of preterm labor, dysmenorrhea and endometritis, suppression of labor at term prior to caesarean delivery, and to facilitate antinatal transport to a medical facility. These compounds are also useful in enhancing fertility rates, enhancing survival rates and synchronizing estrus in farm animals; and may be useful in the prevention and treatment of disfunctions of the oxytocin system in the central nervous system including obsessive compulsive disorder (OCD) and neuropsychiatric disorders.

  该发明提供了新型的取代三环羧酰胺，其作为催产素受体竞争性拮抗剂，并提供其制造方法、药物组合物以及在治疗、抑制、压制或预防早产、痛经和子宫内膜炎、在剖腹产前抑制足月分娩以及促进孕妇前往医疗机构的使用方法。这些化合物还可用于提高农业动物的生育率、提高生存率和同步发情；并且可能有助于预防和治疗中枢神经系统中催产素系统功能障碍，包括强迫症和神经精神障碍。
• Tricyclic pyridyl carboxamides and derivatives thereof tocolytic oxytocin receptor antagonists
  申请人：Wyeth

  公开号：US07064120B2

  公开（公告）日：2006-06-20

  This invention provides novel substituted tricyclic pyridyl carboxamides which act as oxytocin receptor competitive antagonists, as well as methods of their manufacture, pharmaceutical compositions and methods of their use in treatment, inhibition, suppression or prevention of preterm labor, dysmenorrhea, endometritis, suppression of labor at term prior to caesarean delivery, and to facilitate antinatal transport to a medical facility. These compounds are also useful in enhancing fertility rates, enhancing survival rates and synchronizing estrus in farm animals; and may be useful in the prevention and treatment of disfunctions of the oxytocin system in the central nervous system including obsessive compulsive disorder (OCD) and neuropsychiatric disorders.

  本发明提供了一种新型的取代三环吡啶基羧酰胺，其作为催产素受体竞争性拮抗剂，以及它们的制造方法、制药组合物和在治疗、抑制、压制或预防早产、痛经、子宫内膜炎、剖腹产前晚期抑制分娩以及促进孕前转运至医疗设施方面的使用方法。这些化合物还可用于增强农业动物的生育率、生存率和同步发情；并且可能有助于预防和治疗中枢神经系统中催产素系统功能障碍，包括强迫症(OCD)和神经精神障碍。