4379-01-5Relevant academic research and scientific papers
Synthesis and Pharmacological Characterization of Conformationally Restricted Retigabine Analogues as Novel Neuronal Kv7 Channel Activators
Ostacolo, Carmine,Miceli, Francesco,Di Sarno, Veronica,Nappi, Piera,Iraci, Nunzio,Soldovieri, Maria Virginia,Ciaglia, Tania,Ambrosino, Paolo,Vestuto, Vincenzo,Lauritano, Anna,Musella, Simona,Pepe, Giacomo,Basilicata, Manuela Giovanna,Manfra, Michele,Perinelli, Diego Romano,Novellino, Ettore,Bertamino, Alessia,Gomez-Monterrey, Isabel M.,Campiglia, Pietro,Taglialatela, Maurizio
, p. 163 - 185 (2020/01/09)
Kv7 K+ channels represent attractive pharmacological targets for the treatment of different neurological disorders, including epilepsy. In this paper, 42 conformationally restricted analogues of the prototypical Kv7 activator retigabine have been synthesized and tested by electrophysiological patch-clamp experiments as Kv7 agonists. When compared to retigabine (0.93 ± 0.43 μM), the EC50s for Kv7.2 current enhancements by compound 23a (0.08 ± 0.04 μM) were lower, whereas no change in potency was observed for 24a (0.63 ± 0.07 μM). In addition, compared to retigabine, 23a and 24a showed also higher potency in activating heteromeric Kv7.2/Kv7.3 and homomeric Kv7.4 channels. Molecular modeling studies provided new insights into the chemical features required for optimal interaction at the binding site. Stability studies evidenced improved chemical stability of 23a and 24a in comparison with retigabine. Overall, the present results highlight that the N5-alkylamidoindole moiety provides a suitable pharmacophoric scaffold for the design of chemically stable, highly potent and selective Kv7 agonists.
Aliphatic thioacetate deprotection using catalytic tetrabutylammonium cyanide
Holmes, Brian T.,Snow, Arthur W.
, p. 12339 - 12342 (2007/10/03)
A series of thiol-functionalized organic compounds were selected to analyze the scope and efficiency of a new thioacetate deprotection method using catalytic tetrabutylammonium cyanide (TBACN) to effect the transformation of a thioacetate group to a free thiol in the presence of a protic solvent. Particularly attractive are the mild reaction and workup conditions, reduced byproduct formation typically seen using literature methods and yields of greater than 80% for the free aliphatic thiols. This method is effective on aliphatic thiols with trityl, benzyl, p-halo-benzyl, phenethyl, phenoxyethyl, and cyclohexylethyl structural moieties, but it is not effective with thiophenols.
