ADX71743

• 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: ADX71743
• 英文别名: 6-(2,4-Dimethylphenyl)-2-ethyl-4,5,6,7-tetrahydro-1,3-benzoxazol-4-one；6-(2,4-dimethylphenyl)-2-ethyl-6,7-dihydro-5H-1,3-benzoxazol-4-one
• 化学式: C₁₇H₁₉NO₂
• 分子量: 269.343
• InChiKey: CPKZCQHJDFSOJT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  43.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2,4-二甲基苯甲醛 在 dirhodium tetraacetate 、 对甲苯磺酰叠氮 、 sodium ethanolate 、 potassium carbonate 作用下， 以 甲醇 、 乙醇 、 水 、 甲苯 、 乙腈 为溶剂， 反应 24.5h， 生成 ADX71743
  参考文献：
  名称：

  Phasic and Tonic mGlu7 Receptor Activity Modulates the Thalamocortical Network

  摘要：

  Mutation of the metabotropic glutamate receptor type 7 (mGlu7) induces absence -like epileptic seizures, but its precise role in the somatosensory thalamocortical network remains unknown. By combining electrophysiological recordings, optogenetics, and pharmacology, we dissected the contribution of the mGlu7 receptor at mouse thalamic synapses. We found that mGlu7 is functionally expressed at both glutamatergic and GABAergic synapses, where it can inhibit neurotransmission and regulate short-term plasticity. These effects depend on the PDZ-ligand of the receptor, as they are lost in mutant mice. Interestingly, the very low affinity of mGlu7 receptors for glutamate raises the question of how it can be activated, namely at GABAergic synapses and in basal conditions. Inactivation of the receptor activity with the mGlu7 negative allosteric modulator (NAM), ADX71743, enhances thalamic synaptic transmission. In vivo administration of the NAM induces a lethargic state with spindle and/or spike and -wave discharges accompanied by a behavioral arrest typical of absence epileptic seizures. This provides evidence for mGlu7 receptor -mediated tonic modulation of a physiological function in vivo preventing synchronous and potentially pathological oscillations.

  DOI：

  10.3389/fncir.2016.00031

文献信息

• NOVEL HETEROCYCLIC COMPOUNDS AS MODULATORS OF MGLUR7
  申请人：Pragma Therapeutics

  公开号：EP3459939A1

  公开（公告）日：2019-03-27

  The present invention relates to novel heterocyclic compounds. The invention is also directed to compounds which are modulators of the metabotropic glutamate receptors (mGluR), preferably of the metabotropic glutamate receptor subtype 7 ("mGluR7"). The present invention also relates to pharmaceutical composition comprising such compound and their use for the treatment of prevention of disorders associated with glutamate dysfunction.

  本发明涉及新颖的杂环化合物。该发明还涉及调节代谢型谷氨酸受体（mGluR）的化合物，优选是代谢型谷氨酸受体亚型7（"mGluR7"）。本发明还涉及包含这种化合物的药物组合物及其用于治疗或预防与谷氨酸功能障碍相关的疾病的用途。
• HETEROCYCLIC COMPOUNDS AS MODULATORS OF MGLUR7
  申请人：PRAGMA Therapeutics

  公开号：US20220363664A1

  公开（公告）日：2022-11-17

  The present invention relates to novel heterocyclic compounds. The invention is also directed to compounds which are modulators of the metabotropic glutamate receptors (mGluR), preferably of the metabotropic glutamate receptor subtype 7 (“mGluR7”). The present invention also relates to pharmaceutical composition comprising such compounds and their use for the treatment or prevention of disorders associated with glutamate dysfunction or in which metabotropic glutamate receptor, preferably mGluR7 subtype of metabotropic glutamate receptors, is involved.
• [EN] NOVEL HETEROCYCLIC COMPOUNDS AS MODULATORS OF MGLUR7<br/>[FR] NOUVEAUX COMPOSES HÉTÉROCYCLIQUES UTILISÉS EN TANT QUE MODULATEURS DE MGLUR7
  申请人：PRAGMA THERAPEUTICS

  公开号：WO2019063596A1

  公开（公告）日：2019-04-04

  The present invention relates to novel heterocyclic compounds. The invention is also directed to compounds which are modulators of the metabotropic glutamate receptors (m Glu R), preferably of the metabotropic glutamate receptor subtype 7 ("m Glu R7"). The present invention also relates to pharmaceutical composition comprising such compounds and their use for the treatment or prevention of disorders associated with glutamate dysfunction or in which metabotropic glutamate receptor, preferably m Glu R7 subtype of metabotropic glutamate receptors, is involved.
• Phasic and Tonic mGlu7 Receptor Activity Modulates the Thalamocortical Network
  作者：Valériane Tassin、Benoît Girard、Apolline Chotte、Pierre Fontanaud、Delphine Rigault、Mikhail Kalinichev、Julie Perroy、Francine Acher、Laurent Fagni、Federica Bertaso

  DOI：10.3389/fncir.2016.00031

  日期：——

  Mutation of the metabotropic glutamate receptor type 7 (mGlu7) induces absence -like epileptic seizures, but its precise role in the somatosensory thalamocortical network remains unknown. By combining electrophysiological recordings, optogenetics, and pharmacology, we dissected the contribution of the mGlu7 receptor at mouse thalamic synapses. We found that mGlu7 is functionally expressed at both glutamatergic and GABAergic synapses, where it can inhibit neurotransmission and regulate short-term plasticity. These effects depend on the PDZ-ligand of the receptor, as they are lost in mutant mice. Interestingly, the very low affinity of mGlu7 receptors for glutamate raises the question of how it can be activated, namely at GABAergic synapses and in basal conditions. Inactivation of the receptor activity with the mGlu7 negative allosteric modulator (NAM), ADX71743, enhances thalamic synaptic transmission. In vivo administration of the NAM induces a lethargic state with spindle and/or spike and -wave discharges accompanied by a behavioral arrest typical of absence epileptic seizures. This provides evidence for mGlu7 receptor -mediated tonic modulation of a physiological function in vivo preventing synchronous and potentially pathological oscillations.