Six-membered cyclic phosphonate GABA antagonists, 2,5-disubstituted 1,3,2-dioxaphosphorinanes.
The trans isomer of 2-(4-bromophenyl)-5-tert-butyl-2-thiono-1,3,2-dioxaphosphorinane competitively inhibited the specific binding of 35S-tert-butylbicyclophosphorothionate to rat brain membranes with an IC50 value of 0.52 microM, and showed insecticidal activity against houseflies with an LD50 value of 2.4 micrograms/fly. This compound and its analogues acted as noncompetitive GABAA receptor antagonists (NGRAs), and phosphorus-containing cyclohexane skeletons may prove useful for the design of novel NGRAs.
Ozoe
Y
Y
Department of Bioresource Science, Faculty of Agriculture, Shimane University, Japan.
Matsumoto
K
K
Mochida
K
K
Nakamura
T
T
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism; D003510:Cyclohexanes / Q000138:chemical synthesis / Q000378:metabolism / Q000633:toxicity; D005260:Female; D018756:GABA Antagonists / Q000138:chemical synthesis* / Q000378:metabolism / Q000633:toxicity; D006793:Houseflies; D007306:Insecticides / Q000138:chemical synthesis* / Q000378:metabolism / Q000633:toxicity; D007928:Lethal Dose 50; D009682:Magnetic Resonance Spectroscopy; D010753:Phosphoranes / Q000138:chemical synthesis* / Q000378:metabolism / Q000633:toxicity; D051381:Rats; D013329:Structure-Activity Relationship
D019086:Bridged Bicyclo Compounds, Heterocyclic; D003510:Cyclohexanes; D018756:GABA Antagonists; D007306:Insecticides; D010753:Phosphoranes; C037476:tert-butylbicyclophosphorothionate