5-(8-ethynyl-6-(pyridin-2-yl)-4H-benzo[f]imidazo[1,5-a][1,4]diazepin-3-yl)-3-methyl-1,2,4-oxadiazole

• 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-(8-ethynyl-6-(pyridin-2-yl)-4H-benzo[f]imidazo[1,5-a][1,4]diazepin-3-yl)-3-methyl-1,2,4-oxadiazole
• 英文别名: MP-III-085；5-(8-ethynyl-6-pyridin-2-yl-4H-imidazo[1,5-a][1,4]benzodiazepin-3-yl)-3-methyl-1,2,4-oxadiazole
• 化学式: C₂₁H₁₄N₆O
• 分子量: 366.382
• InChiKey: BDFZSOMNQYUCRC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  82
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-羟基乙脒 、 8-乙炔基-6-吡啶-2-基-4H-咪唑[1,5-a] [1,4]苯并二氮杂-3-羧酸乙酯 在 sodium hydride 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 反应 0.25h， 以74%的产率得到5-(8-ethynyl-6-(pyridin-2-yl)-4H-benzo[f]imidazo[1,5-a][1,4]diazepin-3-yl)-3-methyl-1,2,4-oxadiazole
  参考文献：
  名称：

  Synthesis and Characterization of a Novel γ-Aminobutyric Acid Type A (GABA_A) Receptor Ligand That Combines Outstanding Metabolic Stability, Pharmacokinetics, and Anxiolytic Efficacy

  摘要：

  1,4-Benzodiazepines are used in the treatment of anxiety disorders but have limited long-term use due to adverse effects. HZ-166 (2) has been shown to have anxiolytic-like effects with reduced sedative/ataxic liabilities. A 1,3-oxazole KRM-II-81 (9) was discovered from a series of six bioisosteres with significantly improved pharmacokinetic and pharmacodynamic properties as compared to 2. Oxazole 9 was further characterized and exhibited improved anxiolytic-like effects in a mouse marble burying assay and a rat Vogel conflict test.

  DOI：

  10.1021/acs.jmedchem.6b01332

文献信息

• [EN] GABA(A) RECEPTOR MODULATORS AND METHODS TO CONTROL AIRWAY HYPERRESPONSIVENESS AND INFLAMMATION IN ASTHMA<br/>[FR] MODULATEURS DU RÉCEPTEUR GABA(A) ET PROCÉDÉS DE CONTRÔLE DE L'HYPERRÉACTIVITÉ DES VOIES RESPIRATOIRES ET DE L'INFLAMMATION DANS L'ASTHME
  申请人：UWM RES FOUNDATION INC

  公开号：WO2018035246A1

  公开（公告）日：2018-02-22

  Pyrrolobenzodiazepines target alpha-4 and alpha-5 GABAA receptors for use in the treatment of airway hyperresponsiveness and inflammation in asthma. Compounds selectively partition to the peripheral compartment and have reduced CNS effects.

  吡咯苯二氮䓬啉靶向α-4和α-5 GABAA受体，用于治疗哮喘中的气道高反应性和炎症。这些化合物选择性地分配到外周区，减少了中枢神经系统的影响。
• Treatment of cognitive and mood symptoms in neurodegenerative and neuropsychiatric disorders with ALPHA5-containing GABAA receptor agonists
  申请人：UWM Research Foundation, Inc.

  公开号：US10906909B2

  公开（公告）日：2021-02-02

  Provided herein are alpha5-containing GABAA receptor agonists and pharmaceutical compositions and methods of treatment of cognitive and mood symptoms in neurodegenerative and neuropsychiatric disorders using them.

  本文提供了含α5的GABAA受体激动剂和药物组合物，以及使用它们治疗神经退行性疾病和神经精神疾病中的认知和情绪症状的方法。
• Substituted benzo[f]imidazo[1,5-a][1,4]diazepines as GABA(a) receptor modulators
  申请人：UWM Research Foundation, Inc.

  公开号：US11447495B2

  公开（公告）日：2022-09-20

  Substituted benzo[f]imidazo[1,5-α][1,4]diazepines of formula (I′) target alpha-4 and alpha-5 GABAA receptors for use in the treatment of airway hyperresponsiveness and inflammation in asthma. Compounds selectively partition to the peripheral compartment and have reduced CNS effects.

  式（I′）的取代苯并[f]咪唑并[1,5-α][1,4]二氮杂卓针对α-4 和 α-5 GABAA 受体，用于治疗哮喘的气道高反应性和炎症。该化合物可选择性地进入外周区，并减少对中枢神经系统的影响。
• GABA(A) RECEPTOR MODULATORS AND METHODS TO CONTROL AIRWAY HYPERRESPONSIVENESS AND INFLAMMATION IN ASTHMA
  申请人：UWM Research Foundation, Inc.

  公开号：EP3500573B1

  公开（公告）日：2021-10-06
• TREATMENT OF COGNITIVE AND MOOD SYMPTOMS IN NEURODEGENERATIVE AND NEUROPSYCHIATRIC DISORDERS WITH ALPHA5-CONTAINING GABAA RECEPTOR AGONISTS
  申请人：UWM Research Foundation, Inc.

  公开号：US20200181146A1

  公开（公告）日：2020-06-11

  Provided herein are alpha5-containing GABA A receptor agonists and pharmaceutical compositions and methods of treatment of cognitive and mood symptoms in neurodegenerative and neuropsychiatric disorders using them.