Synthesis and structure-activity relationships of a series of insecticidal dioxatricyclododecenes acting as the noncompetitive antagonist of GABAA receptors

Nitrogen Analogues of Aldrin as Noncompetitive Antagonists of GABA_A Receptor

“…The presence of a subsite accepting the electronegative moiety of NGRAs is postulated in the binding site. 5…”

Interactions with the Gamma-Aminobutyric Acid A-Receptor

“…Furthermore, Ozoe et al (1993) showed that the extended structure 4 (Figure 96.10) is highly insecticidal and that compound 5 has intermediate toxicity, which is entirely lost by any chlorination in the norbornene nucleus. Thus, the dioxan (5) loses its housefly toxicity (LD 50 , 5.5 g/g) completely when one-or two-bridge chlorines are introduced and there is evidently a crossover point between the two structural types, because the fully chlorinated but not extended dioxan (6) has the same toxicity, which is much reduced in various partially dechlorinated analogues (see Section 96.4.3 for further discussion).…”

γ-Aminobutyric Acid Receptors: A Rationale for Developing Selective Insect Pest Control Chemicals

“…This discovery came from the observation that the cyclodiene insecticide heptachlor epoxide and g-HCH structurally resemble the first NCA, picrotoxinin (Matsumura and Ghiasuddin 1983). Later, simple dechlorinated cyclic hydrocarbons or lactones were found to retain certain levels of insecticidal and NCA activities on GABARs, indicating that the chlorine atoms are not essential for the action, although they enhance it (Ozoe and Matsumura 1986;Ozoe et al 1993b). Antagonist actions of OC insecticides were clearly demonstrated by electrophysiological studies in addition to initial binding studies.…”

“…5). To reconcile this pharmacophore model and the SARs of EBOB analogs, many hybrids of cyclodienes and EBOB analogs were synthesized (Ozoe et al 1990(Ozoe et al , 1993b. This SAR study led to the suggestion that the NCA binding-site should have an additional pocket (P1) that accommodates the phenyl group of EBOB and related analogs as well as that of 2-phenyl-1,3-dithianes (Fig.…”

“…5). Consequently, the NCA binding-site model consisting of four subsites (P1-P4) was constructed (Ozoe et al 1993b) (Fig. 5).…”