Synthesis and antiviral activity of certain thiazole C-nucleosides

Abstract

A general reaction of glycosyl cyanides with liquid hydrogen sulfide in the presence of 4-dimethylaminopyridine to provide the corresponding glycosylthiocarboxamides is described. These glycosylthiocarboxamides were utilized as the precursors for the synthesis of 2-D-ribofuranosylthiazole-4-carboxamide and 2-beta-D-ribofuranosylthiazole-5-carboxamide (23). The structural modification of 2-beta-D-ribofuranosylthiazole-4-carboxamide (12) into 2-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)thiazole-4-carboxamide (15), 2-beta-D-ribofuranosylthiazole-4-thiocarboxamide (17), and 2-(5-deoxy-beta-D-ribofuranosyl)thiazole-4-carboxamide (19) is also described. These thiazole nucleosides were tested for in vitro activity against type 1 herpes virus, type 3 parainfluenza virus, and type 13 rhinovirus and an in vivo experiment was run against parainfluenza virus. They were also evaluated as potential inhibitors of purine nucleotide biosynthesis. It was shown that the compounds (12 and 15) which possessed the most significant antiviral activity were also active inhibitors (40-70%) of guanine nucleotide biosynthesis.

Broad-spectrum antiviral activity of 2-beta-D-ribofuranosylselenazole-4-carboxamide, a new antiviral agent

“…Preliminary studies of tiazofurin 2 (33) indicated that it possesses a spectrum of antiviral activity in cell culture similar to, but somewhat less potent than, that of ribavirin I (1-P-D-ribofurant Contribution no. 1669, Army Research Program on Antiparasitic Drugs. osyl-1,2,4-triazole-3-carboxamide) and that it has a significant activity against several experimental neoplasms, including those of the lung (15,18,26).…”

Synthesis and antiviral studies of a novel isodideoxynucleoside: an analogue of the antiviral compound, tiazofurin

“…The discovery, that tiazofurin (2-β-D-ribofuranosylthiazole-4-carboxamide, 1 possesses antitumor activity 1 and is also endowed with broad-spectrum antiviral activity, 1,2 led to the synthesis of several tiazofurin derivatives, including analogs 2 and 3. [3][4][5] In more recent studies, a series of isomeric dideoxynucleosides was synthesized in our laboratory.…”

Modulation of nicotinamide adenine dinucleotide and poly(adenosine diphosphoribose) metabolism by the synthetic "C" nucleoside analogs, tiazofurin and selenazofurin. A new strategy for cancer chemotherapy.

“…Abbreviations used in this paper: 3-AB, 3-aminobenzamide; ADPribose, adenosine diphospho-ribose; BCNU, 1,3-bis(2-chloroethyl)-1-nitrosourea; DMS, dimethylsulfate; GMP, guanosine 5'-monophosphate; IMP, inosine 5'-monophosphate; MNNG, N-methyl-N'-nitro-N-nitrosoguanidine; NMN, nicotinamide mononucleotide; SAD, selenazofurinadenine dinucleotide; Sel, selenazofurin; TAD, tiazofurin-adenine dinucleotide; Taz, tiazofurin. boxamide) are synthetic "C" nucleoside analogs with potent antineoplastic activity in experimental murine and human tumors (1)(2)(3)(4)(5). They are highly effective in treating a variety of murine tumors including L1210 leukemia, P388 leukemia, and the highly resistant Lewis lung carcinoma (1)(2)(3)(4).…”

“…boxamide) are synthetic "C" nucleoside analogs with potent antineoplastic activity in experimental murine and human tumors (1)(2)(3)(4)(5). They are highly effective in treating a variety of murine tumors including L1210 leukemia, P388 leukemia, and the highly resistant Lewis lung carcinoma (1)(2)(3)(4). They are also effective in vitro against several human tumors including the human colon adenocarcinoma line LoVo/L and the human promyelocytic leukemia cell line HL-60 (6,7).…”

“…3 compares the effects of these agents on the activity of purified poly(ADP-ribose) polymerase in the presence of two different substrate concenUptakes in control cells were performed at each time point and were essentially the same as the point indicated in each figure at 0 time. Treated cells were incubated in media supplemented with 1 AM Sel (n), 10 AM Sel (i), 1 (24). In the presence of 450 ,MM NAD, Taz and Sel were weak inhibitors producing only 10 and 20% inhibition at inhibitor concentrations of 5 mM.…”