4BP-Tqs

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4BP-Tqs
• 英文别名: 4-(4-bromophenyl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-8-sulfonamide
• 化学式: C₁₈H₁₇BrN₂O₂S
• 分子量: 405.3
• InChiKey: YNCXHXYZTLIZTO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  80.6
• 氢给体数：
  2
• 氢受体数：
  4

文献信息

• METHODS OF TREATING HIV-ASSOCIATED NEUROLOGICAL DISORDERS (HAND)
  申请人：Rosalind Franklin University of Medicine and Science

  公开号：US20220184036A1

  公开（公告）日：2022-06-16

  In the present disclosure, doxycycline-inducible astrocyte-specific HIV Tat transgenic mice (iTat), a surrogate HAND model, were treated with PNU-125096, a positive allosteric modulator of α7 nicotinic acetylcholine receptor (α7 nAChR) and effects on Tat-induced behavioral impairments and neuropathologies were observed. This disclosure shows that PNU-125096 treatment significantly improved locomotor, learning and memory deficits of iTat mice while inhibited glial activation and increased PSD-95 expression in the cortex and hippocampus of iTat mice. α7 nAChR knockout eliminated the protective effects of PNU-125096 on iTat mice. In addition, inhibition of p38 phosphorylation by SB239063, a p38 MAPK-specific inhibitor, exacerbated Tat neurotoxicity in iTat mice. These findings demonstrated for the first time that α7 nAChR activation led to protection against HAND and suggest that α7 nAChR and PNU-125096 hold significant promise for development of therapeutics for HAND.

  在本公开披露中，使用多西环素诱导的星形胶质细胞特异性HIV Tat转基因小鼠（iTat）作为HAND模型，用PNU-125096，α7烟碱乙酰胆碱受体（α7 nAChR）的正向变构调节剂，治疗了这些小鼠，并观察了对Tat诱导的行为障碍和神经病理的影响。本公开披露表明，PNU-125096治疗显著改善了iTat小鼠的运动、学习和记忆障碍，同时抑制了星形胶质细胞的激活，并增加了iTat小鼠皮层和海马体中PSD-95的表达。α7 nAChR基因敲除消除了PNU-125096对iTat小鼠的保护作用。此外，p38 MAPK特异性抑制剂SB239063抑制p38磷酸化，加重了iTat小鼠的Tat神经毒性。这些发现首次证明了α7 nAChR的激活导致对HAND的保护，并表明α7 nAChR和PNU-125096在开发HAND治疗药物方面具有重要的前景。
• LIGANDS FOR ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTORS AND METHODS OF TREATING NEUROLOGICAL AND INFLAMMATORY CONDITIONS
  申请人：Northeastern University

  公开号：EP3180086A1

  公开（公告）日：2017-06-21
• ANTITUSSIVE COMPOSITIONS AND METHODS
  申请人：Attenua, Inc.

  公开号：EP3328383A1

  公开（公告）日：2018-06-06
• COMBINATIONS OF POSITIVE ALLOSTERIC MODULATORS AND NICOTINIC ACETYLCHOLINE RECEPTOR AGONISTS FOR TREATING OCULAR CONDITIONS
  申请人：Oyster Point Pharma, Inc.

  公开号：EP3820443A1

  公开（公告）日：2021-05-19
• Ligands for Alpha-7 Nicotinic Acetylcholine Receptors and Methods of Treating Neurological and Inflammatory Conditions
  申请人：Northeastern University

  公开号：US20170217984A1

  公开（公告）日：2017-08-03

  Compounds are provided which bind to an allosteric site on the mammalian alpha-7 nicotinic acetylcholine receptor (alpha-7 nAChR) and act as positive allosteric modulators with or without allosteric agonist activity. The compounds are useful in diagnosing, preventing, or treating a variety of disorders involving cognition, learning, memory, neurodegeneration, drug addiction, inflammation, chronic pain, and neuropathic pain. The compounds also can be used to enhance memory and learning in normal individuals.