The synthesis of some polycyclic N-H acids with quinoxaline and [1,2,4]triazines1
Iveta Wiedermannová., Michal Otyepkab, Jakub Stýskalaa, and Jan Sloukaa
aDepartment of Organic Chemistry, Palacký University, Tr. Svobody 8, 771 46 Olomouc, Czech Republic
bDepartment of Physical Chemistry, Palacký University, Tr. Svobody 26, 771 46 Olomouc, Czech Republic
(received 26 Jun 03; accepted 13 Nov 03; published on the web 17 Dec 03)
Abstract
3-(4-Aminophenyl)-1,2-dihydro-quinoxaline-2-one (2b), 3-(2-aminophenyl)-6,7-dimethyl-1,2- dihydro-quinoxaline-2-one (1b), its 3-(4-aminophenyl)-isomer (3b), 3-(2-aminobenzyl)-1,2- dihydro-quinoxaline-2-one (4b), its 3-(4-aminobenzyl)-isomer (6b), 3-(2-aminobenzyl)-6,7- dimethyl-1,2-dihydro-quinoxaline-2-one (5b) and its 3-(4-aminobenzyl)-isomer (7b) were diazotised and the resulting diazonium salts were coupled with ethyl cyanoacetylcarbamate, 3- methyl-1,2-dihydro-quinoxaline-2-one, 3,6,7-trimethyl-1,2-dihydro-quinoxaline-2-one and 3- methyl-6,7-dichloro-1,2-dihydro-quinoxaline-2-one. In this manner the corresponding hydrazones with one 1,2-dihydro-quinoxaline-2-one ring (1d, 3d, 5d, 7d) and hydrazones with two 1,2-dihydro-quinoxaline-2-one rings (3e-3g, 4e-4g, 5e-5g, 6e-6g, 7e-7g) were obtained. Cyclization of hydrazones (1d, 3d, 5d, 7d) afforded compounds (1h, 3h, 5h, 7h) containing 6- azauracil and also 1,2-dihydroquinoxaline-2-one rings. The starting amino derivative (1b) was prepared by the reaction of N-acetylisatine with 4,5-dimethyl-o-phenylenediamine followed by hydrolysis of the N-acetyl derivative. The amino derivative (5b) was prepared by the condensation of 2-nitrophenylpyruvic acid with 4,5-dimethyl-o-phenylenediamine and by reduction of the formed nitro derivative (5a). The amino derivative (3b) was prepared by the condensation of 4-acetylaminophenylglyoxylic acid with 4,5-dimethyl-o-phenylenediamine and hydrolysis of the N-acetyl derivative. The amino derivative (7b) resulted from the condensation of 4,5-dimethyl-o-phenylenediamine with 4-aminophenylpyruvic acid.
Keywords: Anti-prion compounds, 1-aryl-6-azauracils, 1,2-dihydroquinoxaline-2-ones
Introduction
Neurological diseases such as Creutsfeldt-Jacob disease, bovine spongiform encephalopathy and scrapie are caused by induced conformational changes of a normal host protein designated as PrPc to an abnormally folded protein designated as PrPSc. Compounds which can affect the conformation of the protein chain could be helpful in treatment of such diseases. The newly discovered anti-prion compounds can be grouped into branched polyamines or rigid condensed heterocycles with tetrapyrrole or acridine skeletons2.
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