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Synthesis and pharmacological screening of derivatives of isoxazolo[4,5-d]pyrimidine

2008; Elsevier BV; Volume: 43; Issue: 11 Linguagem: Inglês

10.1016/j.ejmech.2008.01.035

1768-3254

Edwin Wagner, Kamal Al‐Kadasi, Michał Zimecki, W. Sawka‐Dobrowolska,

Synthesis and Characterization of Heterocyclic Compounds

A number of derivatives of isoxazolo[4,5-d]pyrimidine were prepared with structures similar to that of purine. Condensation of the hydrazide of 4-amino-5-benzoylisoxazolo-3-carboxylic acid 2 with ethyloxalyl chloride followed by cyclization gave 3-oxdiazolo-[1,3,4]-4-amino-5-benzoylisoxazole 7 which, upon cyclization with acetonitrile followed by reactions with different amines, gave derivatives of isoxazolo[4,5-d]pyrimidine 9 and 10d–g. Compounds 8g and 10f were tested for their effects on the immune response in the mouse model. Both compounds significantly inhibited the humoral immune response in vivo to sheep erythrocytes at a dose of 100 μg, whereas in the delayed type hypersensitivity assay a suppressive activity was shown only by compound 10f. In addition, compound 8g inhibited and compound 10f stimulated the proliferative response of mouse splenocytes to concanavalin A. The results indicated that compound 10f was a universal inhibitor of the immune response, while compound 8g selectively suppressed the humoral immune response.