Synthesis and anticonvulsant activity of 6-alkoxy-[1,2,4]triazolo[3,4-a]phthalazines.
A new series of 6-alkoxy-[1,2,4]triazolo[3,4-a]phthalazines (3a-3v) were synthesized and their anticonvulsant activity and neurotoxicity were evaluated by the maximal electroshock test and the rotarod test respectively. Significant anticonvulsant activity was displayed by a number of compounds. The most promising compounds 6-(4-chlorobenzyloxy)-[1,2,4]triazolo[3,4-a]phthalazine (3f) and 6-heptyloxy-[1,2,4]triazolo[3,4-a]phthalazine (3s) showed a median effective dose of 7.1 and 11.0 mg/kg, and had protective index value of 5.2 and 8.0 respectively. The two compounds were further found to have potent activity against seizures induced by pentylenetetrazole, isoniazid, thiosemicarbazide, 3-mercaptopropionic acid but not seizures induced by strychnine, indicating that the two compounds might function by enhancing gamma-aminobutyric acid neurotransmission.
Zhang
Lei
L
Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, Yanbian University College of Pharmacy, Yanji 133000, Jilin Province, China.
Guan
Li-Ping
LP
Sun
Xian-Yu
XY
Wei
Cheng-Xi
CX
Chai
Kyu-Yun
KY
Quan
Zhe-Shan
ZS
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use; D004597:Electroshock; D051379:Mice; D008810:Mice, Inbred C57BL; D010793:Phthalazines / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use; D045442:Rotarod Performance Test; D012640:Seizures / Q000139:chemically induced; D013329:Structure-Activity Relationship
C539545:6-(4-chlorophenoxyl)-(1,2,4)triazolo(3,4-a)phthalazine; C539546:6-heptyloxy-(1,2,4)triazolo(3,4-a)phthalazine; D000927:Anticonvulsants; D010793:Phthalazines