To examine the structural parameters necessary for antiviral efficacy of certain purine nucleosides, several 9-beta-D-ribofuranosylpurine-6-carboxamides have been synthesized. Glycosylation of the Me3Si derivative of purine--6-carboxamide with protected ribofuranose in the presence of a Lewis acid gave the blocked nucleoside which on deprotection furnished 9-beta-D-ribofuranosyl-6-iodopurine with cyanide ion. Certain 2-amino- and 2-methyl-9-beta-D-ribofuranosylpurine-6-carboxamides have also been prepared. 8-Carbamoylguanosine (16) has been prepared by homolytic acylation of the parent nucleoside. These compounds were tested against several RNA and DNA viruses in cell culture. 9-beta-D-Ribofuranosylpurine-6-carboxamide (6a), the corresponding 6-thiocarboxamide (7b), and 4-amino-8-(beta-D-ribofuranosylamino)pyrimido[5,4-d]pyrimidine (8) showed significant in vitro antiviral activity at nontoxic dosage levels. 6a employed in the treatment of Rift Valley fever virus infected mice at 50 (mg/kg)/day gave a 55% survival rate on day 21 compared to a 30% survival in the controls.
Et30-ligroin cuHi2na aAll compounds were analyzed for C, H, and N, and all gave values within 0.3% of the calculated figures.(31%), mp 115-118°. Recrystallization raised the melting point to 121-122°.W-Isopropyl-3-(5-carboxy-2-fuiyl)aciylamide ( 5). The known7 3-(5-carboxymethyl-2-furyl)acrylic acid was converted to the isopropyl amide 4 by the general method described above, and 4 (0.52 g, 2.2 mmol) was dissolved in MeOH (10 ml) and 1% aqueous KOH (16.5 ml) and kept at 25°for 55 min. Acidification and extraction with EtOAc gave crude product (0.48 g) which was crystallized from MeOH-Et20 to give 5, mp 201-203°(0.406 g, 83%).jV-Isopropyl-3-(5-hydroxymethyl-2-furyl)acrylamide ( 7). The known* 3-(5-acetoxymethyl-2-furyl)acrylic acid was converted to the isopropyl amide 6 by the general method described above, and a solution of 6 (7.80 g, 0.031 mol) in 40 ml of MeOH and 21 ml of 10% aqueous KOH was kept at 25°for 30 min. The solution was acidified, and the precipitate was filtered off, washed with water, and dried in vacuo. Crystallization from MeOH-Et20 gave 7 (4.75 g, 73%), mp 182-185°; second crop (1.20 g, 18%), mp 181-183°. Recrystallization from MeOH-Et20 raised the melting point to 185-186°.
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