TY - JOUR
T1 - Synthesis, in vitro pharmacology, and molecular modeling of syn-huprines as acetylcholinesterase inhibitors
AU - Camps, P.
AU - Gómez, E.
AU - Muñoz-Torrero, D.
AU - Badia, A.
AU - Vivas, N. M.
AU - Barril, X.
AU - Orozco, M.
AU - Luque, F. J.
PY - 2001/12/20
Y1 - 2001/12/20
N2 - Two 12-amino-6,7,8,11-tetrahydro-7,11-methanocycloocta[b]quinoline derivatives [9-Me(Et)] (syn-huprines) have been obtained by condensation of known 7-alkylbicyclo[3.3.1]non-6-en-3-ones with 2-(trifluoromethyl)aniline, followed by basic cyclization of the resulting imine, and chromatographic separation of the regioisomeric mixture of products, thus obtained. The new (±)-syn-huprines were shown to be slightly less active bovine or human acetylcholinesterase inhibitors than the corresponding anti-derivatives. Molecular modeling simulations allow us to explain the differences in inhibitory activity of these compounds on the basis of an inverse solvation effect.
AB - Two 12-amino-6,7,8,11-tetrahydro-7,11-methanocycloocta[b]quinoline derivatives [9-Me(Et)] (syn-huprines) have been obtained by condensation of known 7-alkylbicyclo[3.3.1]non-6-en-3-ones with 2-(trifluoromethyl)aniline, followed by basic cyclization of the resulting imine, and chromatographic separation of the regioisomeric mixture of products, thus obtained. The new (±)-syn-huprines were shown to be slightly less active bovine or human acetylcholinesterase inhibitors than the corresponding anti-derivatives. Molecular modeling simulations allow us to explain the differences in inhibitory activity of these compounds on the basis of an inverse solvation effect.
U2 - 10.1021/jm010949b
DO - 10.1021/jm010949b
M3 - Article
SN - 0022-2623
VL - 44
SP - 4733
EP - 4736
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
ER -