161105-48-2Relevant articles and documents
Design, synthesis and biological evaluation of ambenonium derivatives as AChE inhibitors
Bolognesi, Maria Laura,Cavalli, Andrea,Andrisano, Vincenza,Bartolini, Manuela,Banzi, Rita,Antonello, Alessandra,Rosini, Michela,Melchiorre, Carlo
, p. 917 - 928 (2003)
Ambenonium (1), an old AChE inhibitor, is endowed with an outstanding affinity and a peculiar mechanism of action that, taken together, make it a very promising pharmacological tool for the treatment of Alzheimer's disease (AD). Unfortunately, the bisquaternary structure of 1 prevents its passage through the blood brain barrier. In a search of centrally active ambenonium derivatives, we planned to synthesize tertiary amines of 1, such as 2 and 3. In addition, to add new insights into the binding mechanism of the inhibitor, we designed constrained analogues of ambenonium by incorporating the diamine functions into cyclic moieties (4-12). The biological evaluation of the new compounds has been assessed in vitro against human AChE and BChE. All tertiary amine derivatives resulted more than 1000-fold less potent than 1 and, unlike prototype, did not show any selectivity between the two enzymes. This result, because of recent findings concerning the role of BChE in AD, makes our compounds, endowed with a well-balanced profile of AChE/BChE inhibition, valuable candidates for further development. To better clarify the interactions that account for the high affinity of 1, docking simulations and molecular dynamics studies on the AChE-1 complex were also carried out.
Toward the rational design of superoxide dismutase mimics: Mechanistic studies for the elucidation of substituent effects on the catalytic activity of macrocyclic manganese(II) complexes
Riley, Dennis P.,Lennon, Patrick J.,Neumann, William L.,Weiss, Randy H.
, p. 6522 - 6528 (2007/10/03)
Two new isomeric bis(trans-fused cyclohexano) substituted 1,4,7,10,13-pentaazacyclopentadecane ligands and their Mn(II) complexes, 3 and 4, have been synthesized, and their activity as superoxide dismutase (SOD) catalysts has been studied. Complex 3 is an
