Refinement of Structural Leads for Centrally Acting Oxime Reactivators of Phosphylated Cholinesterases*
نویسندگان
چکیده
منابع مشابه
Refinement of structural leads for centrally acting oxime reactivators of phosphylated cholinesterases.
We present a systematic structural optimization of uncharged but ionizable N-substituted 2-hydroxyiminoacetamido alkylamine reactivators of phosphylated human acetylcholinesterase (hAChE) intended to catalyze the hydrolysis of organophosphate (OP)-inhibited hAChE in the CNS. Starting with the initial lead oxime RS41A identified in our earlier study and extending to the azepine analog RS194B, re...
متن کاملNew structural scaffolds for centrally acting oxime reactivators of phosphylated cholinesterases.
We describe here the synthesis and activity of a new series of oxime reactivators of cholinesterases (ChEs) that contain tertiary amine or imidazole protonatable functional groups. Equilibration between the neutral and protonated species at physiological pH enables the reactivators to cross the blood-brain barrier and distribute in the CNS aqueous space as dictated by interstitial and cellular ...
متن کاملTryptoline-3-hydroxypyridinaldoxime conjugates as efficient reactivators of phosphylated human acetyl and butyrylcholinesterases.
Two promising uncharged reactivators for inhibited human BChE and AChE have been described. These compounds show an ability to reactivate VX-inhibited BChE largely superior to those of known pyridinium aldoximes. Moreover, these oximes also exhibit a good ability to reactivate VX-, tabun- and paraoxon-inhibited human AChE.
متن کاملEffect of Centrally Acting a-Adrenergic Agonists
Three studies were undertaken to reevaluate (1) whether there is a peripheral component in the reduction of sympathetic activity caused by centrally acting drugs; and (2) whether the antihypertensive effect of these drugs is due entirely to this reduction. Plasma growth hormone and norepinephrine concentrations were used as respective markers of central a-adrenoceptor stimulation and peripheral...
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ژورنال
عنوان ژورنال: Journal of Biological Chemistry
سال: 2012
ISSN: 0021-9258
DOI: 10.1074/jbc.m111.333732