IA-102 | 763133-41-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: IA-102
• 英文别名: 4-methyl-2-[3-(4-nitrophenyl)-1H-pyrazol-5-yl]phenol
• CAS: 763133-41-1
• 化学式: C₁₆H₁₃N₃O₃
• 分子量: 295.298
• InChiKey: VNEUYJIONLUYIO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  94.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  IA-102 在 亚硝酸特丁酯 、 tin(II) chloride dihdyrate 、 叠氮基三甲基硅烷 作用下， 以 乙醇 、 氘代苯 、 乙腈 为溶剂， 反应 17.0h， 生成 2-[3-[2-(diethylamino)-3H-azepin-5-yl]-1H-pyrazol-5-yl]-4-methylphenol
  参考文献：
  名称：

  Synthesis and Properties of Molecular Probes for the Rescue Site on Mutant Cystic Fibrosis Transmembrane Conductance Regulator

  摘要：

  Cystic fibrosis is a genetic disease caused by mutations in the gene for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. In vitro experiments have demonstrated that 4-methyl-2-(5-phenyl-1H-pyrazol-3-yl)phenol (VRT-532, 1) is able to partially restore the function of mutant CFTR proteins. To help elucidate the nature of the interactions between 1 and mutant CFTR, molecular probes based on the structure of 1 have been prepared. These include a photoreactive aryl azide derivative 11 and a fluorescent dansyl sulfonamide 15. Additionally, a method for hydrogen isotope exchange on 1 has been developed, which could be used for the incorporation of radioactive tritium. Using iodide efflux assays, the probe molecules have been demonstrated to modulate the activity of mutant CFTR in the same manner as 1. These probe molecules enable a number of biochemical experiments aimed at understanding how 1 rescues the function of mutant CFTR. This understanding can in turn aid in the design and development of more efficacious compounds which may serve as therapeutic agents in the treatment of cystic fibrosis.

  DOI：

  10.1021/jm201335c
• 作为产物：
  描述：

  2-羟基-5-甲基苯乙酮 在 吡啶 、 hydrazine hydrate 、 potassium tert-butylate 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 17.5h， 生成 IA-102
  参考文献：
  名称：

  Synthesis and Properties of Molecular Probes for the Rescue Site on Mutant Cystic Fibrosis Transmembrane Conductance Regulator

  摘要：

  Cystic fibrosis is a genetic disease caused by mutations in the gene for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. In vitro experiments have demonstrated that 4-methyl-2-(5-phenyl-1H-pyrazol-3-yl)phenol (VRT-532, 1) is able to partially restore the function of mutant CFTR proteins. To help elucidate the nature of the interactions between 1 and mutant CFTR, molecular probes based on the structure of 1 have been prepared. These include a photoreactive aryl azide derivative 11 and a fluorescent dansyl sulfonamide 15. Additionally, a method for hydrogen isotope exchange on 1 has been developed, which could be used for the incorporation of radioactive tritium. Using iodide efflux assays, the probe molecules have been demonstrated to modulate the activity of mutant CFTR in the same manner as 1. These probe molecules enable a number of biochemical experiments aimed at understanding how 1 rescues the function of mutant CFTR. This understanding can in turn aid in the design and development of more efficacious compounds which may serve as therapeutic agents in the treatment of cystic fibrosis.

  DOI：

  10.1021/jm201335c

文献信息

• Modulators of ATP-Binding Cassette Transporters
  申请人：VanGoor Frederick F.

  公开号：US20100144798A1

  公开（公告）日：2010-06-10

  The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Regulator (“CFTR”), compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

  本发明涉及ATP结合盒（“ABC”）转运蛋白或其片段的调节剂，包括囊性纤维化跨膜调节因子（“CFTR”），以及其组成物和使用这些调节剂的方法。本发明还涉及使用这些调节剂治疗ABC转运蛋白介导的疾病的方法。
• MODULATORS OF ATP-BINDING CASSETTE TRANSPORTERS
  申请人：Van Goor Frederick F.

  公开号：US20120184583A1

  公开（公告）日：2012-07-19

  The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Regulator (“CFTR”), compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

  本发明涉及ATP结合盒（“ABC”）转运蛋白或其片段的调节剂，包括囊性纤维化跨膜调节器（“CFTR”），以及其组成物和使用这些调节剂的方法。本发明还涉及使用这些调节剂治疗ABC转运蛋白介导的疾病的方法。
• Synthesis and Properties of Molecular Probes for the Rescue Site on Mutant Cystic Fibrosis Transmembrane Conductance Regulator
  作者：Bashar Alkhouri、Robert A. Denning、Patrick Kim Chiaw、Paul D. W. Eckford、Wilson Yu、Canhui Li、Jovanka J. Bogojeski、Christine E. Bear、Russell D. Viirre

  DOI：10.1021/jm201335c

  日期：2011.12.22

  Cystic fibrosis is a genetic disease caused by mutations in the gene for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. In vitro experiments have demonstrated that 4-methyl-2-(5-phenyl-1H-pyrazol-3-yl)phenol (VRT-532, 1) is able to partially restore the function of mutant CFTR proteins. To help elucidate the nature of the interactions between 1 and mutant CFTR, molecular probes based on the structure of 1 have been prepared. These include a photoreactive aryl azide derivative 11 and a fluorescent dansyl sulfonamide 15. Additionally, a method for hydrogen isotope exchange on 1 has been developed, which could be used for the incorporation of radioactive tritium. Using iodide efflux assays, the probe molecules have been demonstrated to modulate the activity of mutant CFTR in the same manner as 1. These probe molecules enable a number of biochemical experiments aimed at understanding how 1 rescues the function of mutant CFTR. This understanding can in turn aid in the design and development of more efficacious compounds which may serve as therapeutic agents in the treatment of cystic fibrosis.