196872-17-0Relevant articles and documents
Novel tacrine analogues for potential use against Alzheimer's disease: Potent and selective acetylcholinesterase inhibitors and 5-HT uptake inhibitors
McKenna, Maureen T.,Proctor, George R.,Young, Louise C.,Harvey, Alan L.
, p. 3516 - 3523 (1997)
Several novel analogues of tactine have been synthesized and tested for their ability to inhibit acetylcholinesterase, butyrylcholinesterase, and neuronal uptake of 5-HT (serotonin) and noradrenaline. Changes in the size of the carbocyclic ring of tactine produced modest potency against cholinesterase enzymes. Addition of a fourth ring resulted in compounds with marked selectivity for acetylcholinesterase (AChE) over butyrylcholinesterase [BChE): e.g. 6-amino-4,5-benzo-5H-cyclopenta[1,2-b]-quinoline (14a) had an IC50 of 0.35μM against AChE and 3.1 μM against BChE. Some tetracyclic compounds are 100-400 times more active than tacrine as inhibitors of neuronal uptake of serotonin, in particular 13-amino-6,7-dihydro-5H- benzo[3,4]cyclohepta[1,2-b]quinoline (18), which had an IC50 of 20 nM. These compounds would be expected to facilitate both cholinergic and monoaminergic transmission. They should be worth investigating in models of memory impairment.
