Synthesis, physicochemical and anticonvulsant properties of new N-(pyridine-2-yl) derivatives of 2-azaspiro[4.4]nonane and [4.5]decane-1,3-dione. Part II.
A series of N-(pyridine-2-yl) derivatives of 2-azaspiro[4.4]nonane- (1a-e), 2-azaspiro[4.5]decane- (2a-e) and 6-methyl-2-azaspiro[4.5]decane-1,3-dione (3a-e) were synthesized and tested for their anticonvulsant activity in the maximum electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure threshold tests. To explain the possible mechanism of action, the most active compounds N-(3-methylpyridine-2-yl)-2-azaspiro[4.4]nonane-1,3-dione (1b), N-(3-methylpyridine-2-yl)-2-azaspiro[4.5]decane-1,3-dione (2b), N-(4-methylpyridine-2-yl)-2-azaspiro[4.5]decane-1,3-dione (2c), and N-(3-methylpyridine-2-yl)-6-methyl-2-azaspiro[4.5]decane-1,3-dione (3b) were tested in vitro for their influence on voltage-sensitive calcium channel receptors, however, they revealed low affinities. For all synthesized compounds the lipophilicity was determined by use of RP-TLC method. The correlation between the lipophilicity and anticonvulsant activity was obtained--the higher the lipophilicity the stronger the anticonvulsant efficacy.
Kaminski
Krzysztof
K
Department of Pharmaceutical Chemistry, Jagiellonian University Medical College, Krakow, Poland.
Obniska
Jolanta
J
Zagorska
Agnieszka
A
Maciag
Dorota
D
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D051379:Mice; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D051381:Rats; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D011725:Pyridines