Iodantipyrine: A new antiviral drug

Abstract

Study of the numerous pyrazolone derivatives showed that these compounds are capable, not only of antiinflammatory and analgesic action, but also of increasing the functional activity of cells in a fibroblast culture of human embryo by reducing the duration of all stages in the mitotic cycle. While not producing any direct virucidal effect in the cell cultures (fibroblasts of human embryo, Hep-2, L-41) these compounds nevertheless inhibit the reproduction of some RNA and DNA-containing viruses [1][2][3]. The antiviral effect is increased by introducing halogen atoms, especially iodine, into the aromatic radical of these compounds [4]. The most promising compound in this respect is iodantipyrine (1-phenyl-2,3-dimethyl-4-iodopyrazolone) obtained upon the electrophilic substitution of iodine for hydrogen in position 4 of the antipyrine cycle by interaction of an aqueous antipyrine solution with a free halogen in the presence of weak bases [5].The antiviral activity ofiodantipyrine is most pronounced with respect to nonpoliomyelitis Coxsackie viruses (A13, A18, A21, B1, B4, B6) and ECHO 11, and the viruses of vesicular stomatitis, vernal encephalitis, influenza, and parainfluenza. The inhibiting dose of the drug with respect to some test viruses in the chicken embryo cell culture is 5-10 ~tg/ml, and the chemotherapeutic ratio amounts to 100-200.Iodantipyrine exhibited interferon-stimulating activity in the mice organism and splenocyte cultures, by inducing the production of "late" 13-interferon (whereby the interferon content in the blood serum of mice increases during one day from 8 to 256 IRU50 / ml) that accounts to some extent for the antiviral effect of the drug [4].Study of the immunotropic properties ofiodantipyrine revealed its immunomodulating activity with respect to erythrocytar and viral antigens [6]. With prolonged administration in rats, the drug stimulated the immunity B-chain (increasing the number of antibody-forming cells in the spleen t Siberian Medical University, Tomsk, Russia. 333and the number of lymphocytes in peripheral blood), induced the monocytar branch ofmeduUary hemopoiesis, and favored the accumulation of microlymphocytes in the lymphoid organs and the expression of Fey receptors on mononuclears of the peritoneal exudate.The combination of antiviral, interferonogenic, and immunomodulating activity of iodantipyrme has inspired tests on the models of viral infections. The most important results were obtained on studying the efficiency of iodantipyrine with respect to vernal encephalitis. These data were obtained on mongrel mice inoculated by subcutaneous injections of the vernal encephalitis (Absettarov's strain) at a dose of 10 LDs0. Peroral administration of iodantipyrine at a dose of 50 mg / kg showed a high antiviral effect upon a prophylactic (double) administration and especially upon the therapeutic (11-day schedule) treatment. The loss of test mice in these experiments was 53 and 40%, and the average survival life amounted to 14 and 16 days, respectively. In the control group, 100...

Polyfluoroalkylated antipyrines in Pd-catalyzed transformations

“…The existence of triple bond was affirmed by the presence in the 13 C NMR spectra of the chemical shis at d 76.4-76.6 and 97.8-98.0 ppm, which are typical of two sp-hybridized carbon atoms. 45,58 Biological testing Iodoantipyrine has been known to be applied in the medicinal practice to treat and prevent tick-borne encephalitis, 59,60 inuenza and infections caused by nonpoliomyelitis enteroviruses of Coxsackie and ECHO groups. 60 We evaluated an antiviral activity of the synthesized polyuoroalkyl-containing iodoantipyrines 5a, b, and aryl-3a, g and phenylethynyl-substituted 6a antipyrines against the inuenza virus A/Puerto Rico/8/34 (H1N1) on MDCK cell line (Table 1) using ribavirin as a reference drug according the published procedure.…”

“…45,58 Biological testing Iodoantipyrine has been known to be applied in the medicinal practice to treat and prevent tick-borne encephalitis, 59,60 inuenza and infections caused by nonpoliomyelitis enteroviruses of Coxsackie and ECHO groups. 60 We evaluated an antiviral activity of the synthesized polyuoroalkyl-containing iodoantipyrines 5a, b, and aryl-3a, g and phenylethynyl-substituted 6a antipyrines against the inuenza virus A/Puerto Rico/8/34 (H1N1) on MDCK cell line (Table 1) using ribavirin as a reference drug according the published procedure. 61 Studying the cytotoxicity of compounds on the MDCK cell line, it was found that compounds 5a, 6a have lower cytotoxicity (CC 50 > 815 mM) compared to the derivatives 5b, 3a and 3g.…”