Treatment of anthranilic acid 1 or 3-amino 2-naphthoic acid 5 with butyl isocyanate in THF led to the formation of the ureido derivatives 3 and 7 respectively, which were cyclized to the corresponding diones 4 and 8 by refluxing in DMF, while the treatment of 1 or 5 with butyl isocyanate in DMF afforded the same diones 4 and 8 respectively. Treatment of 2,4-Bis (trimethylsilyloxy) quinazoline 9 with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)quinazoline-2,4(1H-3H)-dione 11. Debenzolation led to the free nucleoside 12. Structural proofs of the prepared compounds are based on spectroscopic methods.
The synthesis of five 4-aminouracil derivatives has been described. These compounds, which are chemically related to xanthines, were tested for possible diuretic activity. The increase in urine output by compounds I, III, and V was comparable to that produced by caffeine in an equimolar dose (5 x 10(-3) M). On the isolated rabbit's heart (Langendorff's preparation), compounds I, III, and V (5 x 10(-5) M) significantly increased the amplitude of contractions without having any significant effect on heart rate. Only these three compounds (4.4 x 10(-8) M) relaxed the isolated rabbit thoracic aorta and rat anococcygeus smooth muscle which were precontracted with norepinephrine (4 x 10(-8) M). This action was not antagonized by atropine, propranolol, or methylene blue, ruling out the involvement of acetylcholine, beta receptors, or endothelium-derived relaxing factor (EDRF). The relaxant effect, however, was reversed by the addition of calcium chloride, suggesting that this relaxation may be due to inhibition of the entry of extracellular calcium into the cells.
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