Novel derivatives of 1,3,4-oxadiazoles are potent mitostatic agents featuring strong microtubule depolymerizing activity in the sea urchin embryo and cell culture assays.

A series of novel 1,3,4-oxadiazole derivatives based on structural and electronic overlap with combretastatins have been designed and synthesized. Initially, we tested all new compounds in vivo using the phenotypic sea urchin embryo assay to yield a number of agents with anti-proliferative, anti-mitotic, and microtubule destabilizing activities. The experimental data led to identification of 1,3,4-oxadiazole derivatives with isothiazole (5-8) and phenyl (9-12) pharmacophores featuring activity profiles comparable to that of combretastatins, podophyllotoxin and nocodazole.

Synthetic utilization of polynitroaromatic compounds. 6. Remarkable regioselectivity in nucleophilic displacement of aromatic nitro groups with amines.

5,7-Dinitroquinazoline-4-ones undergo nucleophilic displacement of a nitro group with N-, S-, and O-nucleophiles. In contrast to previously studied dinitro-substituted benzoannulated five- and seven-membered heterocycles (where a high degree of selectivity was observed), these quinazolines mostly yield mixtures of regioisomeric substitution products. At the same time, primary and secondary amines react selectively to afford 5-aminoquinazolones (peri-substitution).

Synthetic utilization of polynitroaromatic compounds. 3. Preparation of substituted dibenz[b,f][1,4]oxazepine-11(10H)-ones from 2,4,6-trinitrobenzoic acid via nucleophilic displacement of nitro groups.

[Reaction: see text]. 1,3-dinitrodibenz[b,f][1,4]oxazepin-11(10H)-one, prepared by intramolecular displacement of nitro group in N-(2-hydroxyphenyl)-2,4,6-trinitrobenzamide, reacts with O- and S-nucleophiles to yield the products of mono- or bis-substitution of the nitro groups. The nitro group in position 3 is displaced first.