Premium
Synthesis of N ‐(phenoxyalkyl)‐, N ‐{2‐[2‐(phenoxy)ethoxy]ethyl}‐ or N ‐(phenoxyacetyl)piperazine Derivatives and Their Activity Within the Central Nervous System
Author(s) -
Pańczyk Katarzyna,
Pytka Karolina,
Jakubczyk Magdalena,
Rapacz Anna,
Siwek Agata,
GłuchLutwin Monika,
Gryboś Anna,
Słoczyńska Karolina,
Koczurkiewicz Paulina,
Ryszawy Damian,
Pękala Elżbieta,
Budziszewska Bogusława,
StarekŚwiechowicz Beata,
SurajPrażmowska Joanna,
Walczak Maria,
Żesławska Ewa,
Nitek Wojciech,
Bucki Adam,
Kołaczkowski Marcin,
Żelaszczyk Dorota,
Francik Renata,
Marona Henryk,
Waszkielewicz Anna M.
Publication year - 2019
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201902648
Subject(s) - piperazine , chemistry , context (archaeology) , antagonist , in vivo , pharmacology , stereochemistry , receptor , medicine , biochemistry , biology , organic chemistry , paleontology , microbiology and biotechnology
Depression, anxiety and epilepsy share some etiology factors, causing frequently observed multimodal activity of centrally active compounds. This might raise the risk of central adverse effects of potential drugs, but on the other hand ‐ in a light of common comorbidity of these diseases ‐ also make an opportunity for avoiding polypragmasy. The presented study combines rational drug design methods, chemical synthesis, receptor studies and in vivo pharmacological screening (mice, i. p .) in order to obtain new centrally active piperazine derivatives in a context of their potential multimodality, investigate the mechanism of their activity and establish relationship between their structure, molecular mechanism and in vivo central activity(‐ies). The most promising pharmacological profile showed 1‐(2‐(2,5‐dimethylphenoxy)ethyl)‐4‐phenylpiperazine dihydrochloride ( 1 ), which was active in the four‐plate test (anxiolytic‐like activity) at 1.25 mg/kg b.w. and possessed high affinities towards several tested molecular targets (5‐HT 1A K i =35 nM ‐ weak antagonist, 5‐HT 2A K i =121 nM, 5‐HT 7 K i =130 nM ‐ weak antagonist, α 1 K i =82 nM, μ K i =240 nM).