Fluorinated pyridinium oximes as potential reactivators for acetylcholinesterases inhibited by paraoxon organophosphorus agent

Antimycobacterial and antitumor activities of Palladium(II) complexes containing isonicotinamide (isn): X-ray structure of trans-[Pd(N3)2(isn)2]

“…In addition, the existence of terminally coordinated pseudohalides is evidenced in the IR spectra of 2, 3 and 4 by the presence of one single and strong band at 2008 cm À1 (2), 2118 cm À1 (3) and 2258 cm À1 (4), assigned to n as N 3 [34], n as SCN [35] and n as NCO [36] modes, respectively. NMR studies in DMSO-d 6 also support the attachment of isonicotinamide via pyridine-type nitrogen atom. The 1 H NMR spectrum of isonicotinamide (isn) consists of two dublets at 8.71 ppm ( 3 J ¼ 6.0 Hz) and 7.76 ppm ( 3 J ¼ 6.0 Hz), associated to the two adjacent protons present on either side of the pyridine ring, whereas the two broad signals at 8.23 and 7.70 ppm are attributed to the amide protons.…”

“…The angle values are 92.25 (15) for N 4 ePdeN 1 and 87.75 (15) [40]. Another structural parameter of interest is the quasi-linearity and the asymmetry observed for the NeN distances in the azido group coordinated to palladium atom (N 1 eN 2 eN 3 ¼ 174.59 (6) , N 1 eN 2 ¼ 1.130 (7) A and N 2 eN 3 ¼ 1.180 (7) A). It is worth mentioning that the existence of strong intermolecular NeH/O hydrogen bonds are responsible for the selfassembly of the monomers into a two-dimensional supramolecular array, Fig.…”

“…For instance, some isn basedcompounds are promising reactivators for the acetylcholinesterase inhibited by sarin [5] and paraoxon organophosphorus agent [6]. Another relevant property of isn is related to its ability to enhance Sirt1 deacetylase activity by competing with the endogenous Sirt1 inhibitor nicotinamide [7].…”

A comparison of reactivating and therapeutic efficacy of the oxime K203 and its fluorinated analog (KR-22836) with currently available oximes (obidoxime, trimedoxime, HI-6) against tabun in rats and mice

“…Enhanced lipophilicity should facilitate BBB penetration. One way to increase the lipophilicity of oximes is by their fluorination 15,16 . It was described that fluorine substitution can lead to an increase in BBB permeability due to changes in lipophilicity [20][21][22] .…”

“…Unfortunately, the oxime K203, as the other known oximes, especially bispyridinium oximes, has rather low potency to reactivate nerve agent-inhibited AChE in the brain due to its limited penetration across the blood-brain barrier (BBB) 14 . Therefore, the fluorinated analog of the oxime K203, KR-22836 [(E)-1-(4-carbamoylpyridinium)-4-(3-fluoro-4-hydroxyiminomethylpyridinium)-but-2-ene dibromide] was synthesized in the Medicinal Science Division of the Korea Research Institute of Chemical Technology to increase its penetration through the BBB 15,16 .…”