86177-04-0Relevant articles and documents
Novel naphthalene diimides as activatable precursors of bisalkylating agents, by reduction and base catalysis
Di Antonio, Marco,Doria, Filippo,Mella, Mariella,Merli, Daniele,Profumo, Antonella,Freccero, Mauro
, p. 8354 - 8360 (2007)
(Chemical Equation Presented) Mild activation of water-soluble naphthalene diimides (NDIs) as bisalkylating agents has been achieved by base catalysis and by chemical and electrochemical reductions. NDI activation by a single electron reduction represents a novelty in the field of activatable electrophiles. Under mild reduction, induced by S2O42- in aqueous solution, the resulting NDI radical anion (NDI?-) undergoes a monomolecular fragmentation to yield a new transient species, where the NDI radical anion is tethered to a quinone methide moiety. The latter still retains electrophilic properties, reacting with amines, thiols, and ethyl vinyl ether. Owing to the NDI recognition properties, these results represent the first step toward selective and bioactivatable cross-linking agents.
Discovery of a potent non-oxime reactivator of nerve agent inhibited human acetylcholinesterase
de Koning, Martijn Constantijn,Horn, Gabriele,Worek, Franz,van Grol, Marco
, p. 151 - 160 (2018/08/10)
Organophosphorous (OP) compounds (such as nerve agents) inhibit the enzyme acetylcholinesterase (AChE) by covalent phosphylation of a key serine residue in the active site of the enzyme resulting in severe symptoms and ultimately death. OP intoxications are currently treated by administration of certain oxime compounds. The presently fielded oximes reactivate OP-inhibited AChE by liberating the phosphylated serine. Recent research towards new reactivators was predominantly devoted to design, synthesis and evaluation of new oxime-based compounds dedicated to overcoming some of the major limitations such as their intrinsic toxicity, their permanent charge which thwarts penetration of brain tissues and their inability to effectively reactivate all types of nerve agent inhibited AChEs. However, in over six decades of research only limited success has been achieved, indicating that there is a need for alternative classes of compounds that could reactivate OP-inhibited AChE. Recently, a number of non-oxime compounds was discovered in which the 4-amino-2-((diethylamino)methyl)phenol (ADOC) motif proved to be able to reactivate OP-inhibited AChE to some extent. In this paper several structural derivatives of ADOC were synthesized and screened for their ability to reactivate human AChE (hAChE) inhibited by the nerve agents VX, sarin, tabun, cyclosarin and paraoxon. We here disclose that one of those compounds showed a remarkable ability to reactivate OP-inhibited hAChE in vitro and that it is the most potent non-oxime reported to date.
Synthesis and antifilarial activity of N-[4-[[4-alkoxy-3-[(dialkylamino)methyl]phenyl]amino]-2-pyrimidinyl]-N'-ph enylguanidines
Angelo,Ortwine,Worth,Werbel,McCall
, p. 1258 - 1267 (2007/10/02)
A series of N-[4-[[4-alkoxy-3-[(dialkylamino)methyl]phenyl]amino]-2-pyrimidinyl]-N' -phenylguanidines have been synthesized for antifilarial evaluation. Reaction of the appropriate benzenamines with N-cyanoguanidine, followed by condensation of the result
