7-chloro-2H-benzo[b][1,4]oxazine-2,3(4H)-dione | 177944-41-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 7-chloro-2H-benzo[b][1,4]oxazine-2,3(4H)-dione
• 英文别名: 7-Chloro-4,1-benzoxazine-2,3-dione；7-chloro-4H-1,4-benzoxazine-2,3-dione
• CAS: 177944-41-1
• 化学式: C₈H₄ClNO₃
• 分子量: 197.578
• InChiKey: WZPYKVJWJDXWSI-UHFFFAOYSA-N

物化性质

• 密度：
  1.540±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  异烟肼 、 7-chloro-2H-benzo[b][1,4]oxazine-2,3(4H)-dione 以 乙醇 为溶剂， 反应 3.0h， 以58%的产率得到N-(4-chloro-2-hydroxyphenyl)-2-(2-isonicotinoylhydrazinyl)-2-oxoacetamide
  参考文献：
  名称：

  Design, synthesis and antimycobacterial activity of benzoxazinone derivatives and open-ring analogues: Preliminary data and computational analysis

  摘要：

  This study examines in depth benzoxazine nucleus for antimycobacterial property. We synthesized some benzoxazin-2-one and benzoxazin-3-one derivatives, which were tested for activity against a panel of Mycobacterium tuberculosis (Mtb) strains, including H37Ra, H37Rv and some resistant strains. Several compounds displayed a high antimycobacterial activity and the three isoniazid analogue derivatives 8a-c exhibited a MIC range of 0.125-0.250 mu g/mL (0.37-0.75 mu M) against strain H37Ra, therefore lower than the isoniazid reference drug. Two benzoxazin-2-one derivatives, 1c and 5j, together with isoniazid-analogue compound 8a, also revealed low MIC values against resistant strains and proved highly selective for mycobacterial cells, compared to mammalian Vero cells. To predict whether molecule 8a is able to interact with the active site of InhA, we docked it into the crystal structure; indeed, during the molecular dynamic simulation the compound never left the protein pocket. The more active compounds were predicted for ADME properties and all proved to be potentially orally active in humans.

  DOI：

  10.1016/j.bmcl.2019.07.025
• 作为产物：
  描述：

  草酰氯 、 2-氨基-5-氯苯酚 以 甲苯 为溶剂， 反应 2.0h， 以73%的产率得到7-chloro-2H-benzo[b][1,4]oxazine-2,3(4H)-dione
  参考文献：
  名称：

  Design, synthesis and antimycobacterial activity of benzoxazinone derivatives and open-ring analogues: Preliminary data and computational analysis

  摘要：

  This study examines in depth benzoxazine nucleus for antimycobacterial property. We synthesized some benzoxazin-2-one and benzoxazin-3-one derivatives, which were tested for activity against a panel of Mycobacterium tuberculosis (Mtb) strains, including H37Ra, H37Rv and some resistant strains. Several compounds displayed a high antimycobacterial activity and the three isoniazid analogue derivatives 8a-c exhibited a MIC range of 0.125-0.250 mu g/mL (0.37-0.75 mu M) against strain H37Ra, therefore lower than the isoniazid reference drug. Two benzoxazin-2-one derivatives, 1c and 5j, together with isoniazid-analogue compound 8a, also revealed low MIC values against resistant strains and proved highly selective for mycobacterial cells, compared to mammalian Vero cells. To predict whether molecule 8a is able to interact with the active site of InhA, we docked it into the crystal structure; indeed, during the molecular dynamic simulation the compound never left the protein pocket. The more active compounds were predicted for ADME properties and all proved to be potentially orally active in humans.

  DOI：

  10.1016/j.bmcl.2019.07.025

文献信息

• US5597922A
  申请人：——

  公开号：US5597922A

  公开（公告）日：1997-01-28
• [EN] GLYCINE RECEPTOR ANTAGONIST PHARMACOPHORE<br/>[FR] PHARMACOPHORE D'ANTAGONISTES DU RECEPTEUR DE LA GLYCINE
  申请人：STATE OF OREGON, acting by and through THE OREGON STATE BOARD OF HIGHER EDUCATION, acting for and on behalf of THE OREGON HEALTH SCIENCES UNIVERSITY AND THE UNIVERSITY OF OREGON, EUGENE OREGON

  公开号：WO1996004288A1

  公开（公告）日：1996-02-15

  (EN) Methods of treating or preventing neuronal loss associated with stroke, ischemia, CNS trauma, hypoglycemia and surgery, as well as treating neurodegenerative diseases including Alzheimer's disease, amyotropic lateral sclerosis, Huntington's disease and Down's syndrome, treating or preventing the adverse consequences of the hyperactivity of the excitatory amino acids, as well as treating anxiety, chronic pain, convulsions and inducing anesthesia are disclosed by administering to an animal in need of such treatment a compound which has high binding to the glycine receptor.(FR) L'invention se rapporte à des procédés de traitement ou de prévention de la perte neuronale associée à l'attaque, à l'ischémie, aux traumatismes du SNC (système nerveux central), à l'hypoglycémie et aux interventions chirurgicales, ainsi qu'au traitement des maladies dégénératives telles que la maladie d'Alzheimer, la sclérose latérale amyotrophique, la maladie de Huntington et le syndrome de Down, et au traitement ou à la prévention des conséquences fâcheuses de l'hyperactivité des acides aminés excitateurs, et au traitement de l'anxiété, de la douleur chronique, des convulsions et à l'induction d'une anesthésie. Ces procédés consistent à administrer à un animal nécessitant ce type de traitement un composé qui se lie fortement au récepteur de la glycine.
• Design, synthesis and antimycobacterial activity of benzoxazinone derivatives and open-ring analogues: Preliminary data and computational analysis
  作者：Daniele Zampieri、Maria Grazia Mamolo、Julia Filingeri、Sara Fortuna、Alessandro De Logu、Adriana Sanna、Davide Zanon

  DOI：10.1016/j.bmcl.2019.07.025

  日期：2019.9

  This study examines in depth benzoxazine nucleus for antimycobacterial property. We synthesized some benzoxazin-2-one and benzoxazin-3-one derivatives, which were tested for activity against a panel of Mycobacterium tuberculosis (Mtb) strains, including H37Ra, H37Rv and some resistant strains. Several compounds displayed a high antimycobacterial activity and the three isoniazid analogue derivatives 8a-c exhibited a MIC range of 0.125-0.250 mu g/mL (0.37-0.75 mu M) against strain H37Ra, therefore lower than the isoniazid reference drug. Two benzoxazin-2-one derivatives, 1c and 5j, together with isoniazid-analogue compound 8a, also revealed low MIC values against resistant strains and proved highly selective for mycobacterial cells, compared to mammalian Vero cells. To predict whether molecule 8a is able to interact with the active site of InhA, we docked it into the crystal structure; indeed, during the molecular dynamic simulation the compound never left the protein pocket. The more active compounds were predicted for ADME properties and all proved to be potentially orally active in humans.