Novel carbamate cholinesterase inhibitors that release biologically active amines following enzyme inhibition.

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Verheijen JC, Wiig KA, Du S, Connors SL, Martin AN, Ferreira JP, Slepnev VI, Kochendorfer U

Novel carbamate cholinesterase inhibitors that release biologically active amines following enzyme inhibition.

Bioorg Med Chem Lett. 2009 Jun 15;19(12):3243-6. doi: 10.1016/j.bmcl.2009.04.089. Epub 2009 Apr 24.

PubMed ID
19423342 [ View in PubMed
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Abstract

Conjugation of the phenol derived from rivastigmine with amphetamines gave access to novel carbamate cholinesterase inhibitors. All compounds possessed increased affinity and selectivity for AChE compared to rivastigmine and were orally bioavailable. Compound 4a, incorporating d-amphetamine, caused significant inhibition of cholinesterase in vivo at doses that were well tolerated. Release of amphetamine from 4a was demonstrated following in vitro and in vivo inhibition of cholinesterase. Compound 4a was also effective in alleviating scopolamine induced amnesia in a rat passive avoidance model.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
RivastigmineAcetylcholinesteraseIC 50 (nM)2615N/AN/ADetails