Chemoselective Hydrogenation of ...
Type de document :
Article dans une revue scientifique: Article original
DOI :
PMID :
URL permanente :
Titre :
Chemoselective Hydrogenation of 6-alkynyl-3-fluoro-2-pyridinaldoxime: Access to first-in-class 6-alkyl-3-Fluoro-2-pyridinaldoxime as Reactivator of Sarin-Inhibited AChE with increased BBB Permeability.
Auteur(s) :
Baati, R. [Auteur]
Jagadeesh, Y. [Auteur]
Dias, J. [Auteur]
Reddy Nimmakayala, M. [Auteur]
Courageux, C. [Auteur]
Gastellier, A. J. [Auteur]
Jegoux, J. [Auteur]
Coisne, Caroline [Auteur]
Laboratoire de la Barrière Hémato-Encéphalique [LBHE]
Landry, Christophe [Auteur]
Laboratoire de la Barrière Hémato-Encéphalique [LBHE]
Gosselet, Fabien [Auteur]
Laboratoire de la Barrière Hémato-Encéphalique [LBHE]
Hachani, Johan [Auteur]
Laboratoire de la Barrière Hémato-Encéphalique [LBHE]
Goossens, Jean-Francois [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA]
Dehouck, Marie-Pierre [Auteur]
Laboratoire de la Barrière Hémato-Encéphalique [LBHE]
Nachon, F. [Auteur]
Razafindrainibe, F. [Auteur]
Jagadeesh, Y. [Auteur]
Dias, J. [Auteur]
Reddy Nimmakayala, M. [Auteur]
Courageux, C. [Auteur]
Gastellier, A. J. [Auteur]
Jegoux, J. [Auteur]
Coisne, Caroline [Auteur]
Laboratoire de la Barrière Hémato-Encéphalique [LBHE]
Landry, Christophe [Auteur]
Laboratoire de la Barrière Hémato-Encéphalique [LBHE]
Gosselet, Fabien [Auteur]
Laboratoire de la Barrière Hémato-Encéphalique [LBHE]
Hachani, Johan [Auteur]
Laboratoire de la Barrière Hémato-Encéphalique [LBHE]
Goossens, Jean-Francois [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA]
Dehouck, Marie-Pierre [Auteur]
Laboratoire de la Barrière Hémato-Encéphalique [LBHE]
Nachon, F. [Auteur]
Razafindrainibe, F. [Auteur]
Titre de la revue :
Chemistry
Numéro :
26
Pagination :
5035-15044
Éditeur :
European chemical societies publishing
Date de publication :
2020-07-11
ISSN :
1521-3765
Mot(s)-clé(s) :
synthesis design
chemoselective hydrogenation
chemical warfare agents
blood-brain barrier permeability
3-fluoro-2-pyridinaldoximes
chemoselective hydrogenation
chemical warfare agents
blood-brain barrier permeability
3-fluoro-2-pyridinaldoximes
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [en]
Novel 6-alkyl- and 6-alkenyl-3-fluoro-2-pyridinaldoximes have been synthesised by using a mild and efficient chemoselective hydrogenation of 6-alkynyl-3-fluoro-2-pyridinaldoxime scaffolds, without altering the reducible, ...
Lire la suite >Novel 6-alkyl- and 6-alkenyl-3-fluoro-2-pyridinaldoximes have been synthesised by using a mild and efficient chemoselective hydrogenation of 6-alkynyl-3-fluoro-2-pyridinaldoxime scaffolds, without altering the reducible, unprotected, sensitive oxime functionality and the C−F bond. These novel 6-alkyl-3-fluoro-2-pyridinaldoximes may find medicinal application as antidotes to organophosphate poisoning. Indeed, one low-molecular-weight compound exhibited increased affinity for sarin-inhibited acetylcholinesterase (hAChE) and greater reactivation efficiency or resurrection for sarin-inhibited hAChE, compared with those of 2-pyridinaldoxime (2-PAM) and 1-({[4-(aminocarbonyl)pyridinio]methoxy}methyl)-2-[(hydroxyimino)methyl]pyridinium chloride (HI-6), two pyridinium salts currently used as antidote by several countries. In addition, the uncharged 3-fluorinated bifunctional hybrid showed increased in vitro blood–brain barrier permeability compared with those of 2-PAM, HI-6 and obidoxime. These promising features of novel low-molecular-weight alkylfluoropyridinaldoxime open up a new era for the design, synthesis and discovery of central non-quaternary broad spectrum reactivators for organophosphate-inhibited cholinesterases.Lire moins >
Lire la suite >Novel 6-alkyl- and 6-alkenyl-3-fluoro-2-pyridinaldoximes have been synthesised by using a mild and efficient chemoselective hydrogenation of 6-alkynyl-3-fluoro-2-pyridinaldoxime scaffolds, without altering the reducible, unprotected, sensitive oxime functionality and the C−F bond. These novel 6-alkyl-3-fluoro-2-pyridinaldoximes may find medicinal application as antidotes to organophosphate poisoning. Indeed, one low-molecular-weight compound exhibited increased affinity for sarin-inhibited acetylcholinesterase (hAChE) and greater reactivation efficiency or resurrection for sarin-inhibited hAChE, compared with those of 2-pyridinaldoxime (2-PAM) and 1-({[4-(aminocarbonyl)pyridinio]methoxy}methyl)-2-[(hydroxyimino)methyl]pyridinium chloride (HI-6), two pyridinium salts currently used as antidote by several countries. In addition, the uncharged 3-fluorinated bifunctional hybrid showed increased in vitro blood–brain barrier permeability compared with those of 2-PAM, HI-6 and obidoxime. These promising features of novel low-molecular-weight alkylfluoropyridinaldoxime open up a new era for the design, synthesis and discovery of central non-quaternary broad spectrum reactivators for organophosphate-inhibited cholinesterases.Lire moins >
Langue :
Anglais
Audience :
Internationale
Établissement(s) :
Université de Lille
CHU Lille
CHU Lille
Collections :
Date de dépôt :
2023-05-25T03:31:13Z
2023-09-20T06:23:48Z
2023-09-20T06:23:48Z