3-[[5-(2,3-二氯苯基)-1-1H-四氮唑]甲基]吡啶盐酸盐 | 899507-36-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 3-[[5-(2,3-二氯苯基)-1-1H-四氮唑]甲基]吡啶盐酸盐
• 中文别名: 3-[[5-(2,3-二氯苯基)-1H-四唑-1-基]甲基]吡啶；3-[[5-(2,3-二氯苯基)-1H-四唑-1-基]甲基]吡啶盐酸盐；3-[[5-(2,3-二氯苯基)-1H-四唑-1-基]甲基]吡啶单盐酸盐
• 英文名称: A-438079
• 英文别名: 3-(5-(2,3-dichlorophenyl)-1H-tetrazol-1-yl)methylpyridine hydrochloride；A 438079 hydrochloride；3-[[5-(2,3-dichlorophenyl)tetrazol-1-yl]methyl]pyridine;hydrochloride
• CAS: 899507-36-9；899431-18-6
• 化学式: C₁₃H₉Cl₂N₅*ClH
• 分子量: 342.615
• InChiKey: MBTJFFMIPPMRGR-UHFFFAOYSA-N

物化性质

• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  3.51
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  56.5
• 氢给体数：
  1
• 氢受体数：
  4

制备方法与用途

生物活性

A 438079 是一种有效的，选择性的 P2X7 受体拮抗剂，pIC50 值为 6.9。

靶点

pIC50: 6.9 (P2X ₇ receptor)

体外研究

In 1321N1 cells stably expressing rat P2X ₇ receptors, A 438079 blocks BzATP-(10 μM) evoked changes in intracellular calcium concentrations with an IC ₅₀ of 321 nM. A 438079 is also selective for the P2X ₇ receptor, at concentrations up to 100 μM.

体内研究

A 438079 (80 μmol/kg, i.v.) reduces noxious and innocuous evoked activity of different classes of spinal neurons in neuropathic rats. A 438079 (100 and 300 μmol/kg, i.p.) significantly raises withdrawal thresh-olds in both the SNL and CCI models. Intraperitoneal injection of A 438079 (5 and 15 mg/kg) 60 min after triggering seizures reduces seizure severity and neuronal death within the hippocampus. A 438079 has superior neuroprotective effects compared with an equally dose of phenobarbital (25 mg/kg). A 438079 partially but significantly prevents the 6-OHDA-induced depletion of striatal DA stores. Pretreatment with A 438079 reduces nociceptive behaviour scores in the HC model.

反应信息

• 作为产物：
  描述：

  A438079 在 盐酸 作用下， 以 乙醇 为溶剂， 生成 3-[[5-(2,3-二氯苯基)-1-1H-四氮唑]甲基]吡啶盐酸盐
  参考文献：
  名称：

  WO2006/86229

  摘要：

  公开号：

文献信息

• AURIS FORMULATIONS FOR TREATING OTIC DISEASES AND CONDITIONS
  申请人：LICHTER Jay

  公开号：US20090306225A1

  公开（公告）日：2009-12-10

  Disclosed herein are compositions and methods for the treatment of otic disorders with immunomodulating agents and auris pressure modulators. In these methods, the auris compositions and formulations are administered locally to an individual afflicted with an otic disorder, through direct application of the immunomodulating and/or auris pressure modulating compositions and formulations onto the auris media and/or auris interna target areas, or via perfusion into the auris media and/or auris interna structures.

  本文公开了使用免疫调节剂和耳压调节剂治疗耳部疾病的组合物和方法。在这些方法中，通过将免疫调节剂和/或耳压调节剂组合物和配方直接应用于耳媒介和/或耳内靶区，或通过灌注进入耳媒介和/或耳内结构，局部给患有耳部疾病的个体进行治疗。
• Auris Formulations for Treating Otic Diseases and Conditions
  申请人：Otonomy, Inc.

  公开号：US20160228357A1

  公开（公告）日：2016-08-11

  Disclosed herein are compositions and methods for the treatment of otic disorders with immunomodulating agents and auris pressure modulators. In these methods, the auris compositions and formulations are administered locally to an individual afflicted with an otic disorder, through direct application of the immunomodulating and/or auris pressure modulating compositions and formulations onto the auris media and/or auris interna target areas, or via perfusion into the auris media and/or auris interna structures.

  本文介绍了使用免疫调节剂和耳压调节剂治疗耳部疾病的组合物和方法。在这些方法中，通过直接将免疫调节剂和/或耳压调节剂组合物和配方局部应用于患有耳部疾病的个体的耳媒体和/或耳内靶区，或通过灌注到耳媒体和/或耳内结构中。
• P2x7 antagonists as frontline or adjunctive treatment against status epilepticus
  申请人：Royal College of Surgeons in Ireland (RCSI)

  公开号：EP2604265A1

  公开（公告）日：2013-06-19

  P2X7 antagonists as frontline or adjunctive treatment against status epilepticus. It is shown that P2X7 antagonists can be used for frontline or adjunctive treatment for the ameloration or termination of status epilepticus and neonatal seizures, especially refractory status epilepticus or neonatal seizures. Combination with current anticonvulsants, particularly GABA-based anticonvulsants such as benzodiazepines or barbiturates, results in the effective termination of status epilepticus, even when it is refractory.

  将 P2X7 拮抗剂作为治疗癫痫状态的前线药物或辅助药物。研究表明，P2X7 拮抗剂可用于一线或辅助治疗，以缓解或终止癫痫状态和新生儿癫痫发作，尤其是难治性癫痫状态或新生儿癫痫发作。与目前的抗惊厥药（尤其是基于 GABA 的抗惊厥药，如苯二氮卓类药物或巴比妥类药物）联合使用，可有效终止癫痫状态，即使是难治性癫痫状态。
• Auris formulations for treating otic diseases and conditions
  申请人：Otonomy, Inc.

  公开号：US10751281B2

  公开（公告）日：2020-08-25

  Disclosed herein are compositions and methods for the treatment of otic disorders with immunomodulating agents and auris pressure modulators. In these methods, the auris compositions and formulations are administered locally to an individual afflicted with an otic disorder, through direct application of the immunomodulating and/or auris pressure modulating compositions and formulations onto the auris media and/or auris interna target areas, or via perfusion into the auris media and/or auris interna structures.

  本文公开了使用免疫调节剂和耳压调节剂治疗耳部疾病的组合物和方法。在这些方法中，通过将免疫调节剂和/或免疫调节压力调节剂组合物和制剂直接施用到耳道介质和/或耳道间质目标区域，或通过灌注到耳道介质和/或耳道间质结构中，对耳道疾病患者进行局部给药。
• Auris formulations for treating OTIC diseases and conditions
  申请人：Otonomy, Inc.

  公开号：US11123285B2

  公开（公告）日：2021-09-21

  Disclosed herein are compositions and methods for the treatment of otic disorders with immunomodulating agents and auris pressure modulators. In these methods, the auris compositions and formulations are administered locally to an individual afflicted with an otic disorder, through direct application of the immunomodulating and/or auris pressure modulating compositions and formulations onto the auris media and/or auris interna target areas, or via perfusion into the auris media and/or auris interna structures.

  本文公开了使用免疫调节剂和耳压调节剂治疗耳部疾病的组合物和方法。在这些方法中，通过将免疫调节剂和/或免疫调节压力调节剂组合物和制剂直接施用到耳道介质和/或耳道间质目标区域，或通过灌注到耳道介质和/或耳道间质结构中，对耳道疾病患者进行局部给药。