5-(1-benzothiophen-2-yl)-8-methyl-1,9-dihydro-2H-[1,3]ox-azolo[4,5-h][2,3]benzodiazepin-2-one | 1398496-52-0

• 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-(1-benzothiophen-2-yl)-8-methyl-1,9-dihydro-2H-[1,3]ox-azolo[4,5-h][2,3]benzodiazepin-2-one
• 英文别名: 5-(1-benzothien-2-yl)-8-methyl-1,9-dihydro-2H-[1,3]oxazolo[4,5-h][2,3]benzodiazepin-2-one；5-(1-Benzothiophen-2-yl)-8-methyl-1,9-dihydro-[1,3]oxazolo[4,5-h][2,3]benzodiazepin-2-one；5-(1-benzothiophen-2-yl)-8-methyl-1,9-dihydro-[1,3]oxazolo[4,5-h][2,3]benzodiazepin-2-one
• CAS: 1398496-52-0
• 化学式: C₁₉H₁₃N₃O₂S
• 分子量: 347.397
• InChiKey: PFRNKLACBZOGIV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  25
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  91.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-(2-hydroxypropyl)-1,3-benzoxazol-2(3H)-one 在 盐酸 、 Jones reagent 、 高氯酸 、 一水合肼 作用下， 以 水 、 乙酸乙酯 、 异丙醇 、 丙酮 为溶剂， 反应 40.17h， 生成 5-(1-benzothiophen-2-yl)-8-methyl-1,9-dihydro-2H-[1,3]ox-azolo[4,5-h][2,3]benzodiazepin-2-one
  参考文献：
  名称：

  A novel GABAA alpha 5 receptor inhibitor with therapeutic potential

  摘要：

  Novel 2,3-benzodiazepine and related isoquinoline derivatives, substituted at position 1 with a 2-benzothiophenyl moiety, were synthesized to produce compounds that potently inhibited the action of GABA on heterologously expressed GABA(A) receptors containing the alpha 5 subunit (GABA(A) alpha(5)), with no apparent affinity for the benzodiazepine site. Substitutions of the benzothiophene moiety at position 4 led to compounds with drug-like properties that were putative inhibitors of extra-synaptic GABA(A) alpha(5) receptors and had substantial blood-brain barrier permeability. Initial characterization in vivo showed that 8-methyl-5-[4-(trifluoromethyl)-1-benzothiophen-2-yl]-1,9-dihydro-2H-[1,3]oxazolo[4,5-h][2,3] benzodiazepin-2-one was devoid of sedative, pro-convulsive or motor side-effects, and enhanced the performance of rats in the object recognition test. In summary, we have discovered a first-in-class GABA-site inhibitor of extra-synaptic GABA(A) alpha(5) receptors that has promising drug-like properties and warrants further development. (C) 2015 Elsevier B.V. All rights reserved

  DOI：

  10.1016/j.ejphar.2015.07.005

文献信息

• DIHYDRO-OXAZOLOBENZODIAZEPINONE COMPOUNDS, A PROCESS FOR THERE PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
  申请人：LING István

  公开号：US20120232065A1

  公开（公告）日：2012-09-13

  Compounds of formula (I): wherein: R 1 represents a hydrogen atom or an alkyl group; R 2 represents an alkyl group; R 3 represents an aryl or heteroaryl group. Medicinal products containing the same which are useful in the treatment or prevention of psychiatric and neurological disorders characterised by cognitive deficits.

  式(I)的化合物：其中：R1代表氢原子或烷基基团；R2代表烷基基团；R3代表芳基或杂环芳基。含有该化合物的药物产品对治疗或预防以认知缺陷为特征的精神疾病和神经系统疾病具有用处。
• Dérivés de dihydro-oxazolobenzodiazépinone, procédés de leur préparation et compositions pharmaceutiques contenant ces composés
  申请人：Les Laboratoires Servier

  公开号：EP2497774B1

  公开（公告）日：2013-10-16
• US8778932B2
  申请人：——

  公开号：US8778932B2

  公开（公告）日：2014-07-15
• A novel GABAA alpha 5 receptor inhibitor with therapeutic potential
  作者：István Ling、Balázs Mihalik、Lori-An Etherington、Gábor Kapus、Adrienn Pálvölgyi、Gábor Gigler、Szabolcs Kertész、Attila Gaál、Katalin Pallagi、Péter Kiricsi、Éva Szabó、Gábor Szénási、Lilla Papp、László G. Hársing、György Lévay、Michael Spedding、Jeremy J. Lambert、Delia Belelli、József Barkóczy、Balázs Volk、Gyula Simig、István Gacsályi、Ferenc A. Antoni

  DOI：10.1016/j.ejphar.2015.07.005

  日期：2015.10

  Novel 2,3-benzodiazepine and related isoquinoline derivatives, substituted at position 1 with a 2-benzothiophenyl moiety, were synthesized to produce compounds that potently inhibited the action of GABA on heterologously expressed GABA(A) receptors containing the alpha 5 subunit (GABA(A) alpha(5)), with no apparent affinity for the benzodiazepine site. Substitutions of the benzothiophene moiety at position 4 led to compounds with drug-like properties that were putative inhibitors of extra-synaptic GABA(A) alpha(5) receptors and had substantial blood-brain barrier permeability. Initial characterization in vivo showed that 8-methyl-5-[4-(trifluoromethyl)-1-benzothiophen-2-yl]-1,9-dihydro-2H-[1,3]oxazolo[4,5-h][2,3] benzodiazepin-2-one was devoid of sedative, pro-convulsive or motor side-effects, and enhanced the performance of rats in the object recognition test. In summary, we have discovered a first-in-class GABA-site inhibitor of extra-synaptic GABA(A) alpha(5) receptors that has promising drug-like properties and warrants further development. (C) 2015 Elsevier B.V. All rights reserved