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In this paper we describe two new basic conditions for the synthesis of quinoxaline 1,4-dioxide derivatives in moderate to good yields. These conditions, exemplified by the use of K2C03 in acetone or KF/A1203 in the absence of an organic solvent, were reproducible and applicable to the synthesis of 2-(carboethoxy)-3-phenylquinoxaline 1,4-dioxide derivatives substituted in position 4 with electron-donating or electron-withdrawing groups.

The synthesis of new cyclic compounds, arylethanolamine derivatives, with potential beta3-adrenoceptor agonist selectivity, which are associated with thermogenesis and regulation of insulin release, are described. Oxazolidine, oxazolidin-2-one, and perhydro-1,4-oxazine derivatives were obtained. The preliminary evaluation of the pharmacological effects of some of the synthesized compounds showed an activation of lypolysis in rat adipocytes with potency and efficiency similar to that observed for other accredited beta3-adrenergic agonists.

Starting with 3-aminoindole-2-carbohydrazide 1 a series of arylidene hydrazones 2 was obtained with good yields (79–85%). Upon treating 2 with nitrous acid a series of 3-arylidineamino-5H-1,2,3-triazino[5,4-b]indol-4-ones 3 was obtained (80–86%). The reaction of 4-methoxybenzylidene derivative 3e with hydrazine hydrate, in ethanol, gave 3-amino-5H-1,2,3-triazino[5,4-b]indol-4-one 4 (64%). However, by treating 3e in boiling hydrate, 3-aminoindole-2-carbaldehyde azine 5 was obtained (44%). By boiling 1 in N,N-dimethylformamide, 3-amino-5H-pyrimido[5,4-b]indol-4-one, 6 was obtained (52%).

This paper describes the synthesis of the previously unknown 11H-1,2,4-triazolo[4,3-b]pyridazino[4,5-b]indoles (2) and 11H-tetrazolo[4,5-b]pyridazino[4,5-b]indoles (3) from 4-hydrazino-5H-pyridazino[4,5-b]indoles (1), as well as the synthesis of 1,2,4-triazolo[3,4-f]-1,2,4-triazino-[4,5-a]indoles (10) from 2-indolecarbohydrazide (4). Compounds 2 were obtained by acylation of compounds 1, followed of thermal cyclization and compounds 3 by treating compounds 1 with nitrous acid. The reactions of compound 4 with formic acid or ethyl orthoformiate gave 1,2-dihydro-1-oxo-1,2,4-triazino[4,5-a]indole (6). Treating this last compound with phosphorus oxychloride or phosphorus pentasulfide, followed by hydrazine, gave 1-hydrazino-1,2,4-triazino-[4,5-a]indole (9). Acylation of this last compound, followed of cyclization gave compounds 10. All the compounds were characterized by elemental analysis and ir and 1H-nmr spectra.

This paper describes the synthesis of 1-chloro-4-hydrazino-5H-pyridazino[4,5-b]indole (4) and some of the triazoles (6–8), tetrazoles (10–11), triazolotetrazoles (9) and bis-tetrazoles (12) derived from it. All of these were previously unknown compounds. Treating 1,4-dioxo-1,2,3,4-tetrahydro-5H-pyridazino[4,5-b]indole (1) with phosphorus oxychloride gave 1,4-dichloro-5H-pyridazino[4,5-b]indole (2), which reacts regioselectively with hydrazine to give compound 4. The reactions of 4 with formic and acetic acids gave 6-chloro-11 H-1,2,4-triazolo[4,3-b]pyridazino[4,5-b]indoles (6a-6b), respectively. Reaction of compound 6a with hydrazine gave 6-hydrazino-11H-1,2,4-triazolo[4,3–6]-pyridazino[4,5,-b]indole (8). This with nitrous acid gave 6-azido-11H-1,2,4-triazolo[4,3-b]pyridazino[4,5-b]-indole (9). Compound 4 reacted with nitrous acid to give 6-chloro-11H-tetrazolo[4,5-b]pyridazino[4,5-b]-indole (10), which gave 1,4-diazydo-5H-pyridazino[4,5-b]indole (12), through successive reactions with hydrazine and nitrous acid. All compounds were characterized by elemental analysis, ir and 1H-nmr spectra.