Quaternary Salts of E2020 Analogues as Acetylcholinesterase Inhibitors for the Reversal of Neuromuscular Block

Clark, John K.; Cowley, Phill; Muir, Alan W.; Palin, Ronald; Pow, Eleanor; Prosser, Alan; Taylor, Robert T.; Zhang, Ming‐Qiang

doi:10.1016/s0960-894x(02)00482-1

Cited by 22 publications

(15 citation statements)

References 9 publications

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“…The experimental biological potency for this benzylpiperidine derivative assayed in HuAChE is reported with different values such as pIC 50 ¼ 7.74 M (IC 50 ¼ 18 nM) [65] and pIC 50 ¼ 8.10 M (IC 50 ¼ 8 nM) [35], but both are in the range from 5.59 to 9.48 M of biological potency of training and test sets. We should note that the experimental pIC 50 values reported for E2020 do not mention its stereochemistry (absolute configuration), and probably are derived from the racemate (rac) (i.e.…”

Section: Prediction Of the Biological Potency (Pic 50 ) Of An Externamentioning

confidence: 99%

“…Moreover, the literature does not report the experimental potency of the pure (R) and (S) enantiomers of E2020, probably because the enantiomers are interconverted in the biological medium [66]. Therefore, we calculated hypothetical pIC 50Exp values for the R enantiomer, using the pIC 50Exp from the racemate [35,65], considering two hypotheses: the R and S enantiomers are equipotent and the R enantiomer is the eutomer.…”

Section: Prediction Of the Biological Potency (Pic 50 ) Of An Externamentioning

confidence: 99%

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Receptor-dependent (RD) 3D-QSAR approach of a series of benzylpiperidine inhibitors of human acetylcholinesterase (HuAChE)

Araújo

Brito

Hoelz

et al. 2011

European Journal of Medicinal Chemistry

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Section: Prediction Of the Biological Potency (Pic 50 ) Of An Externamentioning

confidence: 99%

Section: Prediction Of the Biological Potency (Pic 50 ) Of An Externamentioning

confidence: 99%

Receptor-dependent (RD) 3D-QSAR approach of a series of benzylpiperidine inhibitors of human acetylcholinesterase (HuAChE)

Araújo

Brito

Hoelz

et al. 2011

European Journal of Medicinal Chemistry

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“…In the search for new methods of reversal of non‐depolarising neuromuscular block at Organon Laboratories in Newhouse, Scotland (now part of Schering Plough), studies were started with new anticholinesterase inhibitors [14, 15]. These were disappointing because the new compounds retained the muscarinic side effects observed with the older traditional cholinesterase inhibitors.…”

Section: The Birth Of An Ideamentioning

confidence: 99%

Cyclodextrins and the emergence of sugammadex

Booij

2009

Anaesthesia

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Residual paralysis, with its subsequent postoperative pulmonary sequelae, is one of the major complications of anaesthesia, and was recognised shortly after the introduction of neuromuscular blocking drugs into routine clinical practice. Although its incidence decreased with the introduction of intermediate duration drugs, and further diminished with routine neuromuscular monitoring and reversal with cholinesterase inhibitors, residual paralysis still remained a problem. In the search for alternatives to stop the effect of neuromuscular blocking drugs and to match their duration of action to clinical need, chelation of the non-depolarising neuromuscular blocking drugs was considered. It was recognised that cyclodextrins could encapsulate steroidal molecules and thereby inactivate the aminosteroidal neuromuscular blocking drugs. In order to improve the binding of rocuronium to the cyclodextrin and to increase the compound's water solubility, the molecule was modified. This led to the development of sugammadex (Org 25969), a modified gamma-cyclodextrin. The modification of the molecule and the initial in vitro studies that led to in vivo and later human studies of this conceptually new drug for anaesthesia are described.

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“…Moreover, if this feature combines with the aromaticity, an additional interaction with an aromatic moiety of AChE will happen . In accord with these findings, several compounds with positively charged substituted nitrogen have been synthesized . In view of the above structural characteristics of the enzyme‐inhibitors interaction and to achieve dual binding site inhibitors, some N ‐substituted heteroarylidene methyl pyridinium compounds were designed and synthesized as potential dual AChE‐BuChE inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Some New 3‐Coumaranone and Coumarin Derivatives as Dual Inhibitors of Acetyl‐ and Butyrylcholinesterase

Alipour

Khoobi

Nadri

et al. 2013

Archiv der Pharmazie

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A series of dithiocarbamates were synthesized and evaluated for their anticholinesterase activity. The most potent acetylcholinesterase inhibitor was found as compound 2g followed by compounds 2f and 2j when compared with donepezil. Compounds 2f and 2g were also more effective than donepezil on butyrylcholinesterase inhibition. Kinetic analysis and molecular docking studies of the most active compound 2g were also carried out.

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Quaternary Salts of E2020 Analogues as Acetylcholinesterase Inhibitors for the Reversal of Neuromuscular Block

Cited by 22 publications

References 9 publications

Receptor-dependent (RD) 3D-QSAR approach of a series of benzylpiperidine inhibitors of human acetylcholinesterase (HuAChE)

Receptor-dependent (RD) 3D-QSAR approach of a series of benzylpiperidine inhibitors of human acetylcholinesterase (HuAChE)

Cyclodextrins and the emergence of sugammadex

Synthesis of Some New 3‐Coumaranone and Coumarin Derivatives as Dual Inhibitors of Acetyl‐ and Butyrylcholinesterase

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