Potent and selective inhibitors of the TASK-1 potassium channel through chemical optimization of a bis-amide scaffold
TASK-1 is a two-pore domain potassium channel that is important to modulating cell excitability, most notably in the context of neuronal pathways. In order to leverage TASK-1 for therapeutic benefit, its physiological role needs better characterization; however, designing selective inhibitors that avoid the closely related TASK-3 channel has been challenging. In this study, a series of bis-amide derived compounds were found to demonstrate improved TASK-1 selectivity over TASK-3 compared to reported inhibitors. Optimization of a marginally selective hit led to analog 35 which displays a TASK-1 IC 50 = 16 nM with 62-fold selectivity over TASK-3 in an orthogonal electrophysiology assay.
Flaherty, Daniel P.,Simpson, Denise S.,Miller, Melissa,Maki, Brooks E.,Zou, Beiyan,Shi, Jie,Wu, Meng,McManus, Owen B.,Aubé, Jeffrey,Li, Min,Golden, Jennifer E.
p. 3968 - 3973
(2014/09/03)
N-Acylthiourea and N-Acylurea Inhibitors of the Hedgehog Protein Signalling Pathway
The present invention relates to the use of acylthiourea or acylurea derivatives for the treatment of pathologies involving a tissue dysfunction associated with a deregulation of the Hedgehog protein signalling pathway, and also to novel acylthiourea or a
-
Page/Page column 14
(2011/11/13)
A mild and efficient procedure for the conversion of aromatic carboxylic esters to secondary amides
A mild and efficient procedure has been developed for the conversion of aromatic carboxylic esters to secondary amides using reusable Zn dust with microwave heating in the presence of N,N-dimethylformamide or conventional heating by stirring in an oil bath using THF as solvent. Zn dust can be reused several times after simple washing with dil. HC1 and distilled water.
Arora, Revika,Paul, Satya,Gupta, Rajive
p. 1137 - 1140
(2007/10/03)
More Articles about upstream products of 6282-15-1