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Synthesis, physicochemical and anticonvulsant properties of new N-phenylamino derivatives of 2-azaspiro[4.4]nonane- and [4.5]decane-1,3-diones: part V.

Authors :
Kamiński K
Obniska J
Dybała M
Source :
European journal of medicinal chemistry [Eur J Med Chem] 2008 Jan; Vol. 43 (1), pp. 53-61. Date of Electronic Publication: 2007 Mar 18.
Publication Year :
2008

Abstract

The synthesis, physicochemical and pharmacological properties of new N-phenylamino derivatives of 2-azaspiro[4.4]nonane-1,3-dione (8-10), 2-azaspiro[4.5]decane-1,3-dione (11-18) and 3-cyclohexyl-pyrrolidine-2,5-dione (19, 20) derivatives were described. The anticonvulsant properties of those compounds were examined by a maximal electroshock (MES) and a pentylenetetrazole (scPTZ) tests, and their neurotoxicity was determined using a rota-rod test. The most active was N-[(2,4-dichlorophenyl)-amino]-2-azaspiro[4.4]nonane-1,3-dione (9), which exhibited anti-seizure properties in the MES model at a dose of 100mg/kg in mice and at a dose of 30mg/kg in rats. To explain the possible mechanism of action, for chosen active derivatives N-[(2,4-dichlorophenyl)-amino]-2-azaspiro[4.4]nonane-1,3-dione (9), N-[(4-bromophenyl)-amino]-2-azaspiro[4.4]nonane-1,3-dione (10), N-[(2,4-dichlorophenyl)-amino]-2-azaspiro[4.5]decane-1,3-dione (12) and N-[(4-bromophenyl)-amino]-2-azaspiro[4.5]decane-1,3-dione (13) their influence on GABA(A) receptors were tested in vitro. Moreover, for all compounds obtained the lipophilic properties were determined by use of RP-HPLC method.

Details

Language :
English
ISSN :
0223-5234
Volume :
43
Issue :
1
Database :
MEDLINE
Journal :
European journal of medicinal chemistry
Publication Type :
Academic Journal
Accession number :
17475369
Full Text :
https://doi.org/10.1016/j.ejmech.2007.02.024