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Synthesis, CYP 450 evaluation, and docking simulation of novel 4‐aminopyridine and coumarin derivatives
Author(s) -
Ghalehshahi Hajar G.,
Balalaie Saeed,
Sohbati Hamid R.,
Azizian Homa,
Alavijeh Mohammad S.
Publication year - 2019
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201800247
Subject(s) - chemistry , coumarin , docking (animal) , hydrazide , stereochemistry , amide , pyrone , pyridine , molecular model , combinatorial chemistry , organic chemistry , medicine , nursing
Four series of novel compounds based on 4‐aminopyridine, glatiramer acetate, pyrone, and coumarin backbones were sufficiently synthesized and identified by spectroscopic methods. CYP enzyme inhibition assays of five predominate human P450 isozymes indicate that all compounds, except for 4‐hydrazide pyridine 1c , seem to be less toxic than 4‐aminopyridine. Further investigation of the compounds using molecular docking experiments revealed different, the same, or stronger binding modes for most of the synthesized compounds, with both polar and hydrophobic interactions with the 1WDA and 1J95 receptors compared to benzoyl l ‐arginine amide and 4‐aminopyridine, respectively. These results introduce the synthesized compounds as K + channel blockers that could be considered for in vivo CNS disease studies.