Singh, Sangeeta; Syme, Colin A.; Singh, Ashvani K.; Devor, Daniel C.; Bridges, Robert J. published the artcile< Benzimidazolone activators of chloride secretion: potential therapeutics for cystic fibrosis and chronic obstructive pulmonary disease>, Synthetic Route of 112-63-0, the main research area is chloride channel benzimidazolone preparation cystic fibrosis; structure activity benzimidazolone lung disease cystic fibrosis.
The diseases of cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) are characterized by mucus-congested airways. Agents that stimulate the secretion of Cl- are anticipated to facilitate mucociliary clearance and thus be of benefit in the treatment of CF and COPD. Recently 1-EBIO (1-ethyl-2-benzimidazolinone or 1-ethyl-1,3-dihydro-2H-benzimidazol-2-one) was shown to stimulate chloride secretion albeit at relatively high concentrations (0.6-1 mM). The studies reported here were undertaken to develop a more potent benzimidazolone. Structure activity studies with 30 benzimidazolone derivatives revealed that Et and hydrogen groups at the 1 and 3 nitrogen positions, resp., were critical for the activation of hIK1 K+ channels and that other alkyl groups were not tolerated at these positions without some loss in potency. Substitutions at the 5 and 6 positions improved the potency of 1-EBIO. Compared with 1-EBIO, the most potent of these derivatives, DCEBIO (5,6-dichloro-1-ethyl-1,3-dihydro-2H-benzimidazol-2-one) was severalfold better in a 86Rb+ uptake assay, 20-fold better in short circuit current measurements on T84 monolayers, and 100-fold better in patch-clamp assays of hIK1 activity. Short circuit current studies revealed DCEBIO stimulates Cl- secretion via the activation of hIK1 K+ channels and the activation of an apical membrane Cl- conductance. The improved potency of DCEBIO strengthens the possibility that compounds in this class may be of therapeutic benefit in the treatment of CF and COPD.
Journal of Pharmacology and Experimental Therapeutics published new progress about Chloride channel openers. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Synthetic Route of 112-63-0.
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