methyl 6-amino-3-cyclopropyl-4-oxo-3,4-dihydro-1,2,3-benzotriazine-7-carboxylate | 1134102-09-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并-1,2,3-三嗪类化合物
• 英文名称: methyl 6-amino-3-cyclopropyl-4-oxo-3,4-dihydro-1,2,3-benzotriazine-7-carboxylate
• 英文别名: methyl 6-amino-3-cyclopropyl-4-oxo-1,2,3-benzotriazine-7-carboxylate
• CAS: 1134102-09-2
• 化学式: C₁₂H₁₂N₄O₃
• 分子量: 260.252
• InChiKey: MVHPMPDLYUVJLL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  97.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-氨基-3-丁炔 、 dimethyl 2-(formylamino)-5-nitrobenzene-1,4-dicarboxylate 、 methyl 6-amino-3-cyclopropyl-4-oxo-3,4-dihydro-1,2,3-benzotriazine-7-carboxylate 生成 methyl 3-but-3-yn-1-yl-6-(formylamino)-4-oxo-3,4-dihydro-1,2,3-benzotriazine-7-carboxylate
  参考文献：
  名称：

  3-SUBSTITUTED-1,2,3-TRIAZIN-4-ONE'S AND 3 SUBSTITUTED 1,3-PYRIMIDINONE'S FOR ENHANCING GLUTAMATERGIC SYNAPTIC RESPONSES

  摘要：

  本发明涉及化合物、药物组合物和方法，用于预防和治疗脑血液不足，包括增强大脑网络中负责基本和高级行为的突触中受体功能。这些大脑网络参与调节呼吸和认知能力，与记忆障碍相关，如多种痴呆症观察到的那样，以及在不同大脑区域之间的神经活动失衡中，如帕金森病、精神分裂症、呼吸抑制、睡眠呼吸暂停、注意力缺陷多动障碍和情感或情绪障碍中，以及神经营养因子缺乏有关的疾病，以及呼吸方面的疾病，如酒精、鸦片、阿片、巴比妥酸盐、麻醉剂或神经毒素过量，或呼吸抑制是由中枢性睡眠呼吸暂停、中风引起的中枢性睡眠呼吸暂停、阻塞性睡眠呼吸暂停、先天性低通气综合征、肥胖性低通气综合征、婴儿猝死综合征、雷特综合征、脊髓损伤、创伤性脑损伤、切尼-斯托克斯呼吸、温迪恩氏诅咒、普拉德-威利综合征和溺水等医学情况引起的。在特定方面，本发明涉及用于治疗此类疾病的化合物以及使用这些化合物进行此类治疗的方法。

  公开号：

  US20100267728A1
• 作为产物：
  描述：

  dimethyl 2-(formylamino)phenyl-1,4-dicarboxylate 在 盐酸 、 硫酸 、 palladium 10% on activated carbon 、 氢气 、 硝酸 、 sodium nitrite 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， -10.0~20.0 ℃ 、344.75 kPa 条件下， 反应 3.0h， 生成 methyl 6-amino-3-cyclopropyl-4-oxo-3,4-dihydro-1,2,3-benzotriazine-7-carboxylate 、 methyl 3-cyclopropyl-6-(formylamino)-4-oxo-3,4-dihydro-1,2,3-benzotriazine-7-carboxylate
  参考文献：
  名称：

  Benzobistriazinones and related heterocyclic ring systems as potent, orally bioavailable positive allosteric AMPA receptor modulators

  摘要：

  AMPA receptors (AMPARs) are an important therapeutic target in the CNS. A series of substituted benzobistriazinone, benzobispyrimidinone and related derivatives have been prepared with high potency and selectivity for the allosteric binding site of AMPARs. Further improvements have been made to previously reported series of positive AMPAR modulators and these compounds exhibit excellent in vivo activity and improved in vivo metabolic stability with up to 100% oral bioavailability in rat. (C) 2011 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2011.09.132

文献信息

• [EN] 3-SUBSTITUTED 1,2,3-TRIAZIN-4-ONE'S AND 3-SUBSTITUTED 1,3-PYRIMIDINONE'S FOR ENHANCING GLUTAMATERGIC SYNAPTIC RESPONSES<br/>[FR] 1,2,3-TRIAZINE-4-ONES 3-SUBSTITUÉES ET 1,3-PYRIMIDINONES 3-SUBSTITUÉES POUR AMÉLIORER LES RÉPONSES SYNAPTIQUES GLUTAMATERGIQUES
  申请人：CORTEX PHARMA INC

  公开号：WO2009038752A3

  公开（公告）日：2009-07-09
• 3-SUBSTITUTED 1,2,3-TRIAZIN-4-ONE'S AND 3-SUBSTITUTED 1,3-PYRIMIDINONE'S FOR ENHANCING GLUTAMATERGIC SYNAPTIC RESPONSES
  申请人：CORTEX PHARMACEUTICALS, INC.

  公开号：EP2195303A2

  公开（公告）日：2010-06-16
• Benzobistriazinones and related heterocyclic ring systems as potent, orally bioavailable positive allosteric AMPA receptor modulators
  作者：Rudolf Mueller、Stanislaw Rachwal、Mark A. Varney、Steven A. Johnson、Kashinatham Alisala、Sheng Zhong、Yong-Xin Li、Peter Haroldsen、Todd Herbst、Leslie J. Street

  DOI：10.1016/j.bmcl.2011.09.132

  日期：2011.12

  AMPA receptors (AMPARs) are an important therapeutic target in the CNS. A series of substituted benzobistriazinone, benzobispyrimidinone and related derivatives have been prepared with high potency and selectivity for the allosteric binding site of AMPARs. Further improvements have been made to previously reported series of positive AMPAR modulators and these compounds exhibit excellent in vivo activity and improved in vivo metabolic stability with up to 100% oral bioavailability in rat. (C) 2011 Published by Elsevier Ltd.
• 3-SUBSTITUTED-1,2,3-TRIAZIN-4-ONE'S AND 3 SUBSTITUTED 1,3-PYRIMIDINONE'S FOR ENHANCING GLUTAMATERGIC SYNAPTIC RESPONSES
  申请人：Mueller Rudolf

  公开号：US20100267728A1

  公开（公告）日：2010-10-21

  This invention relates to compounds, pharmaceutical compositions and methods for use in the prevention and treatment of cerebral insufficiency, including enhancement of receptor functioning in synapses in brain networks responsible for basic and higher order behaviors. These brain networks, which are involved in regulation of breathing, and cognitive abilities related to memory impairment, such as is observed in a variety of dementias, in imbalances in neuronal activity between different brain regions, as is suggested in disorders such as Parkinson's disease, schizophrenia, respiratory depression, sleep apneas, attention deficit hyperactivity disorder and affective or mood disorders, and in disorders wherein a deficiency in neurotrophic factors is implicated, as well as in disorders of respiration such as overdose of an alcohol, an opiate, an opioid, a barbiturate, an anesthetic, or a nerve toxin, or where the respiratory depression results form a medical condition such as central sleep apnea, stroke-induced central sleep apnea, obstructive sleep apnea, congenital hypoventilation syndrome, obesity hypoventilation syndrome, sudden infant death syndrome, Rett syndrome, spinal cord injury, traumatic brain injury, Cheney-Stokes respiration, Ondines curse, Prader-Willi's syndrome and drowning. In a particular aspect, the invention relates to compounds useful for treatment of such conditions, and methods of using these compounds for such treatment.

  本发明涉及化合物、药物组合物和方法，用于预防和治疗脑血液不足，包括增强大脑网络中负责基本和高级行为的突触中受体功能。这些大脑网络参与调节呼吸和认知能力，与记忆障碍相关，如多种痴呆症观察到的那样，以及在不同大脑区域之间的神经活动失衡中，如帕金森病、精神分裂症、呼吸抑制、睡眠呼吸暂停、注意力缺陷多动障碍和情感或情绪障碍中，以及神经营养因子缺乏有关的疾病，以及呼吸方面的疾病，如酒精、鸦片、阿片、巴比妥酸盐、麻醉剂或神经毒素过量，或呼吸抑制是由中枢性睡眠呼吸暂停、中风引起的中枢性睡眠呼吸暂停、阻塞性睡眠呼吸暂停、先天性低通气综合征、肥胖性低通气综合征、婴儿猝死综合征、雷特综合征、脊髓损伤、创伤性脑损伤、切尼-斯托克斯呼吸、温迪恩氏诅咒、普拉德-威利综合征和溺水等医学情况引起的。在特定方面，本发明涉及用于治疗此类疾病的化合物以及使用这些化合物进行此类治疗的方法。