Six-membered Cyclic Phosphonate GABA Antagonists, 2, 5-Disubstituted 1, 3, 2-Dioxaphosphorinanes

Abstract

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. 52μM, and showed insecticidal activity against houseflies with an LD₅₀ value of 2.4μg/fly. This compound and its analogues acted as noncompetitive GABA_A receptor antagonists (NGRAs), and phosphorus-containing cyclo-hexane skeletons may prove useful for the design of novel NGRAs.