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Benzene‐1,2‐, 1,3‐, and 1,4‐di‐ N ‐substituted carbamates as conformationally constrained inhibitors of acetylcholinesterase
Author(s) -
Lin MingCheng,
Hwang MeiTing,
Chang HanGing,
Lin ChungSheng,
Lin Gialih
Publication year - 2007
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.20202
Subject(s) - chemistry , acetylcholinesterase , benzene , stereochemistry , benzene derivatives , enzyme , medicinal chemistry , organic chemistry , biochemistry , in vitro , chemical synthesis
Benzene‐1,2‐, 1,3‐, and 1,4‐di‐ N ‐substituted carbamates (1–15) are synthesized as the conformationally constrained inhibitors of acetylcholinesterase and mimic gauche , eclipsed , and anti ‐conformations of acetylcholine, respectively. All carbamates 1–15 are characterized as the pseudo substrate inhibitors of acetylcholinesterase. For a series of geometric isomers, the inhibitory potencies are as follows: benzene‐1,4‐di‐ N ‐substituted carbamate ( para compound) > benzene‐1,3‐di‐ N ‐substituted carbamate ( meta compound) > benzene‐1,2‐di‐ N ‐substituted carbamate ( ortho compound). Therefore, benzene‐1,4‐di‐ N ‐substituted carbamates ( para compounds), with the angle of 180° between two C(benzene)–O bonds, mimic the preferable anti C–O/C–N conformers of acetylcholine for the choline ethylene backbone in the acetylcholinesterase catalysis. © 2007 Wiley Periodicals, Inc. J Biochem Mol Toxicol 21:348–353, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/jbt.20202