1343487-95-5Relevant academic research and scientific papers
A Rational Design of a Selective Inhibitor for Kv1.1 Channels Prevalent in Demyelinated Nerves That Improves Their Impaired Axonal Conduction
Al-Sabi, Ahmed,Daly, Declan,Hoefer, Patrick,Kinsella, Gemma K.,Metais, Charles,Pickering, Mark,Herron, Caroline,Kaza, Seshu Kumar,Nolan, Kieran,Dolly, J. Oliver
, p. 2245 - 2256 (2017)
K+ channels containing Kv1.1 α 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-pyrrolyl)methane 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·2HCl] (8) selectively blocked Kv1.1 channels (IC50 ≈ 15 μM) recombinantly expressed in mammalian cells, induced a positive shift in the voltage dependency of K+ 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.
5,5-Diaryldipyrromethanes: Syntheses and anion binding properties
Gowri Sreedevi,Thomas, Ajesh P.,Salini,Ramakrishnan,Anju,Derry Holaday,Reddy,Suresh,Srinivasan
supporting information; experimental part, p. 5995 - 5999 (2011/11/28)
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 in
