Structure-activity relationships in a new series of insecticidally active dioxatricycloalkenes derived by structural comparison of the GABA antagonists bicycloorthocarboxylates and endosulfan

Polycyclic dinitriles: a novel class of potent GABAergic insecticides provides a new radioligand, [3H]BIDN

“…The pharmacophore model proposed in this study shares much with a number of other models which have been proposed for the GABA convulsant site (Soloway, 1965;Milbrath et al, 1979;Klunk et al, 1983;Ticku and Maksay, 1983;Ozoe and Matsumura, 1986;Matsumura et al, 1987;Wong and Andrews, 1989;Ozoe et al, 1990;Watanabe et al, 1990;Mullin, 1991;Paramonov et al, 1990;Calder et al, 1993;Lees and Calder, 1996;Akamatsu et al, 1997). There are some differences however, particularly with respect to the placement of the isopropenyl group of picrotoxinin in this model compared to the model of Akamatsu (Akamatsu eta/., 1997).…”

Interactions with the Gamma-Aminobutyric Acid A-Receptor

“…Attempts to simplify the orthobenzoate ring system of these potent cage convulsants and the search for structural changes to confer selective toxicity in favor of mammals versus insects produced numerous insecticidal dithianes, oxathianes, and their sulfoxides and sulfones (Palmer and Casida, 1995;Wacher et al, 1992). Figure 96.10 further shows the convergence of structural changes between partly (Brooks and Mace, 1987) and totally (Ozoe et al, 1990) dechlorinated alpha-endosulfan (1, Figure 96.10) (which surprisingly retains measurable housefly toxicity (LD 50 , ca. 43 g/g; 20-fold less toxic than alpha-endosulfan, when co-applied with sesoxane), the toxic t-butyl trioxabicyclooctanes (TBOs) such as 2 (Figure 96.10) , and the dithianes described by Elliott et al (1992).…”

“…With the possibility of oxidation at sulfur in vivo, which may enforce additional conformational rigidity and also increase binding propensity, the situation becomes more complex (see Section 96.4.3). (Brooks and Mace, 1987;Ozoe et al, 1990Ozoe et al, , 1993, the trioxabicyclooctane-derived cage convulsants, and the more recent dioxans and dithianes (Pulman et al, 1996). The bracketed number following a chemical number or structure is the housefly topical LD 50 (g/g; measured in the presence of sesoxane or piperonyl butoxide).…”

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

“…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.…”