Herve Dumas

Synthesis and potential antiallergic activity of new pteridinones and related compounds

Summary The synthesis and pharmacological profile of a series of 2-alkoxy and 2-phenoxymethyl-3 H -pteridin-4-ones and related compounds are described. These compounds displayed antiallergic activity in the passive cutaneous anaphylaxis test in rats. In contrast to both sodium cromoglycate and nedocromil sodium, many of our compounds were active when administered orally. The most potent in this series, 2-ethoxymethyl-3 H -pteridin-4-one 2b (LCB 2183) was investigated in other models of allergy and inflammation. The antiallergic activity was confirmed and interesting antiinflammatory properties were observed. It was therefore selected for further development as a human therapeutic agent.

Synthèse et activité hypo-uricémiante de nouvelles ptéridines

Resume A series of new pteridines and 3,4-dihydropteridines with substitution in position 2, showed a hypouricemic activity in rats. After a single oral administration in this species, the hypouricemic effect of 2-(methoxymethoxymethyl)-3,4-dihydropteridine maleate 26b and 2-(2,2,2-trifluoroethoxymethyl)-3,4-dihydropteridine maleate 32b is as potent as that of 1H-pyrazolo[3,4-d]pyrimidin-4-ol (allopurinol). We showed a long-lasting fall of uricemia in further investigation of compound 26b; this fall can reach 80%. Compound 26b, unlike allopurinol, is not an in vitro xanthine oxidase inhibitor, but the ex vivo inhibition could be proved. It could be useful in the treatment of fout in human beings.