di-p-tolyldi(2-pyrrolyl)methane | 1343487-95-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: di-p-tolyldi(2-pyrrolyl)methane
• 英文别名: 5,5-di(p-tolyl)dipyrromethane；2-[bis(4-methylphenyl)-(1H-pyrrol-2-yl)methyl]-1H-pyrrole
• CAS: 1343487-95-5
• 化学式: C₂₃H₂₂N₂
• 分子量: 326.441
• InChiKey: TUINXMOUNMOEGO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  31.6
• 氢给体数：
  2
• 氢受体数：
  0

反应信息

• 作为反应物：
  描述：

  di-p-tolyldi(2-pyrrolyl)methane 在 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 2.08h， 生成
  参考文献：
  名称：

  A Rational Design of a Selective Inhibitor for Kv1.1 Channels Prevalent in Demyelinated Nerves That Improves Their Impaired Axonal Conduction

  摘要：

  K+ channels containing Kv1.1 alpha subunits, which become prevalent at internodes in demyelinated axons, may underlie their dysfunctional conduction akin to muscle weakness in multiple sclerosis. Small inhibitors were sought with selectivity for the culpable hyper-polarizing K+ currents. Modeling of interactions with the extracellular pore in a Kv1.1-deduced structure identified diaryldi(2-pyrrolyeinethane as a suitable scaffold with optimized alkyl ammonium side chains. The resultant synthesized candidate [2,2'-((5,5'(di-p-topyldiaryldi(2-pyrrolyl)methane)bis(2,2'-carbonyl)bis(azanediyl)) diethaneamine center dot 2HCl] (8) selectively blocked Kv1.1 channels (IC50 approximate to 15 mu M) recombinantly expressed in mammalian cells, induced a positive shift in the voltage dependency of K4 current activation, and slowed its kinetics. It preferentially inhibited channels containing two or more Kv1.1 subunits regardless of their positioning in concatenated tetramers. In slices of corpus callosum from mice subjected to a demyelination protocol, this novel inhibitor improved neuronal conduction, highlighting its potential for alleviating symptoms in multiple sclerosis.

  DOI：

  10.1021/acs.jmedchem.6b01262
• 作为产物：
  描述：

  吡咯 、 4,4'-二甲基二苯甲酮 在 三氟化硼乙醚 作用下， 以 甲醇 为溶剂， 反应 120.08h， 以50%的产率得到di-p-tolyldi(2-pyrrolyl)methane
  参考文献：
  名称：

  A Rational Design of a Selective Inhibitor for Kv1.1 Channels Prevalent in Demyelinated Nerves That Improves Their Impaired Axonal Conduction

  摘要：

  K+ channels containing Kv1.1 alpha subunits, which become prevalent at internodes in demyelinated axons, may underlie their dysfunctional conduction akin to muscle weakness in multiple sclerosis. Small inhibitors were sought with selectivity for the culpable hyper-polarizing K+ currents. Modeling of interactions with the extracellular pore in a Kv1.1-deduced structure identified diaryldi(2-pyrrolyeinethane as a suitable scaffold with optimized alkyl ammonium side chains. The resultant synthesized candidate [2,2'-((5,5'(di-p-topyldiaryldi(2-pyrrolyl)methane)bis(2,2'-carbonyl)bis(azanediyl)) diethaneamine center dot 2HCl] (8) selectively blocked Kv1.1 channels (IC50 approximate to 15 mu M) recombinantly expressed in mammalian cells, induced a positive shift in the voltage dependency of K4 current activation, and slowed its kinetics. It preferentially inhibited channels containing two or more Kv1.1 subunits regardless of their positioning in concatenated tetramers. In slices of corpus callosum from mice subjected to a demyelination protocol, this novel inhibitor improved neuronal conduction, highlighting its potential for alleviating symptoms in multiple sclerosis.

  DOI：

  10.1021/acs.jmedchem.6b01262

文献信息

• 5,5-Diaryldipyrromethanes: syntheses and anion binding properties
  作者：K.C. Gowri Sreedevi、Ajesh P. Thomas、P.S. Salini、S. Ramakrishnan、K.S. Anju、M.G. Derry Holaday、M.L.P. Reddy、C.H. Suresh、A. Srinivasan

  DOI：10.1016/j.tetlet.2011.08.163

  日期：2011.11

  A two-step synthesis of 5,5-diaryldipyrromethanes in good yields is described. The adopted synthetic strategy can be used to tune the substituent at the meso-carbon very easily by choosing the Grignard reagent of interest. Further, the influence of the incorporation of various diaryl units at the mesa-carbon atom in the inherent anion binding affinities of the dipyrromethanes through hydrogen bonding was discussed. (C) 2011 Elsevier Ltd. All rights reserved.
• A Rational Design of a Selective Inhibitor for Kv1.1 Channels Prevalent in Demyelinated Nerves That Improves Their Impaired Axonal Conduction
  作者：Ahmed Al-Sabi、Declan Daly、Patrick Hoefer、Gemma K. Kinsella、Charles Metais、Mark Pickering、Caroline Herron、Seshu Kumar Kaza、Kieran Nolan、J. Oliver Dolly

  DOI：10.1021/acs.jmedchem.6b01262

  日期：2017.3.23

  K+ channels containing Kv1.1 alpha subunits, which become prevalent at internodes in demyelinated axons, may underlie their dysfunctional conduction akin to muscle weakness in multiple sclerosis. Small inhibitors were sought with selectivity for the culpable hyper-polarizing K+ currents. Modeling of interactions with the extracellular pore in a Kv1.1-deduced structure identified diaryldi(2-pyrrolyeinethane as a suitable scaffold with optimized alkyl ammonium side chains. The resultant synthesized candidate [2,2'-((5,5'(di-p-topyldiaryldi(2-pyrrolyl)methane)bis(2,2'-carbonyl)bis(azanediyl)) diethaneamine center dot 2HCl] (8) selectively blocked Kv1.1 channels (IC50 approximate to 15 mu M) recombinantly expressed in mammalian cells, induced a positive shift in the voltage dependency of K4 current activation, and slowed its kinetics. It preferentially inhibited channels containing two or more Kv1.1 subunits regardless of their positioning in concatenated tetramers. In slices of corpus callosum from mice subjected to a demyelination protocol, this novel inhibitor improved neuronal conduction, highlighting its potential for alleviating symptoms in multiple sclerosis.