Imino 1,2,3,4-tetrahydrocyclopent[b]indole carbamates as dual inhibitors of acetylcholinesterase and monoamine oxidase

Synthesis and pharmacological evaluation of donepezil-based agents as new cholinesterase/monoamine oxidase inhibitors for the potential application against Alzheimer’s disease

“…Thus, multi-target-directed ligand (MTDL) raises as an effective strategy for the treatment of AD 24,25 . Attempts to combine anti-AChE and anti-MAO activities in one molecular entity have previously been reported 26 . For example, Npyrimidine-4-acetylaniline derivatives possessing AChE and reversible MAO-A inhibitory activity in vitro have been reported, and our group has also reported the synthesis of tacrine-coumarin hybrids as multitargeted agents against AD [27][28][29] .…”

Multifunctional Enzyme Inhibition for Neuroprotection - A Focus on MAO, NOS, and AChE Inhibitors

“…This compound is currently in phase II clinical trials for Alzheimer's disease and diffuse Lewy body disease and will eventually be tested for Parkinson's disease as well. The most exciting information obtained from structure-affinity and structure-selectivity relationship analyses performed during this study was that the R 2 substituent ortho to the carbamate moiety affected both enzymatic activities, leading to the multi-active compounds 2-5 [126]. The synthetic iminic intermediates (2-5, Fig.…”

Recent Advances in the Development of Hybrid Molecules/Designed Multiple Compounds with Antiamnesic Properties

“…In a first approach the structural motive of the AChE inhibitor physostigmine (6) was combined with the one of the irreversible MAO inhibitors selegiline (8) and rasagiline (9) to yield dual inhibitors like (10) [17]. In a first approach the structural motive of the AChE inhibitor physostigmine (6) was combined with the one of the irreversible MAO inhibitors selegiline (8) and rasagiline (9) to yield dual inhibitors like (10) [17].…”

“…In a first approach the structural motive of the AChE inhibitor physostigmine (6) was combined with the one of the irreversible MAO inhibitors selegiline (8) and rasagiline (9) to yield dual inhibitors like (10) [17]. Halogen substitution ortho to the carbamate moiety turned out to be responsible for a strong activity increase [17]. Structural modification led to the identification of several combined inhibitors like compound (11), which show high affinity at AChE and both MAOs.…”

“…Further development of these kinds of compounds was terminated due to low oral activity either due to poor oral availibility or poor penetration of the blood-brain barrier (BBB) [17].…”