L. Messini

8-Aza-analogues of PMEA and PMEG: Synthesis and In Vitro Anti-HIV Activity

Abstract 8-Aza-analogues of the potent antiviral nucleotide analogues 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA) and 9-[2-(phosphonomethoxy)-ethyl]guanine (PMEG) were prepared and evaluated for activity against human immunodeficiency viruses. When compared to the parent compounds, 8-aza-PMEA (1) and -PMEG (2) were less cytotoxic for MT-4 cells, but also less potent against HIV-1 and HIV-2. A new synthesis of PMEG starting from guanine is also reported.

8-Aza Derivatives of 3-Deazapurine Nucleosides. Synthesis and in vitro Evaluation of Antiviral and Antitumor Activity

The syntheses of 4-amino-1-(β-D-ribofuranosyl)-1H-1,2,3-triazolo[4,5-c]pyridine (8-aza-3-deazaadenosine, 1), 4-amino-1-(2-deoxy-β-D-erythro-pentofuranosyl)-1H-1,2,3-triazolo[4,5-c]pyridine (2′-deoxy-8-aza-3-deazaadenosine, 2), and their N8 and N7 glycosylated analogues (12,13, 21,22) and 4-amino-1-(2,3-dideoxy-β-D-erythro-pentof uranosyl)-1H-1,2,3-triazolo [4,5-c]pyridine (2′,3′-dideoxy-8-aza-3-deazaadenosine, 3) were carried out by glycosylation of the 4-chloro-3H-1,2,3-triazolo[4,5-c]pyridine anion. The anomeric configuration as well as the position of glycosylation were determined by 1H-, 13C-NMR, UV and N.O.E. difference spectroscopy. Nucleoside (2) and its parent compound 2′-deoxy-3-deazaadenosine were found active against ASFV and VSV. The 4-chloro-2-(β-D-ribofuranosyl)-2H-1,2,3-triazolo[4,5-c] pyridine (9) was active against Coxsackie B1, whereas none of the 8-aza-3-deaza purine nucleosides, compound (3) included, was active against HIV-1. The 6-chloro derivatives of 8-aza-3-deazapurine ribo- and 2′-deoxyribonucleosides (11) and (20) showed some activity against LoVo human colon adenocarcinoma.

8-Aza-1-deazapurine Nucleosides as Antiviral Agents

Abstract 2′,3′-Dideoxy-8-aza-1-deazaadenosine (21) and its α-anomer (20) were synthesized via glycosylation of 7-chloro-3H-1,2,3-triazolo[4,5-b]pyridi-ne with 2,3-dideoxy-5-O-[(1, 1)-dimethylethyl)diphenylsilyl]-D-glycero-o-pen-tofuranosyl chloride. The reaction gave a mixture of α- and β-anomers of N3-, N4- and N1-glycosylated regioisorners (12–15). The α- and β-anomers of the N4-glycosylated isomer 26 and 27 were also synthesized through the glycosylation of 8-aza-1-deazaadenine with 1-acetoxy-2,3-dideoxy-5-O-f(1,1-di-methylethyl)dimethylsilyl]-D-glycero-pentouranose. These dideoxynucleo-sides and a series of previously synthesized 8-aza-1-deazapurine nucleosidcs were tested for activity against several DNA and RNA viruses, HIV-1 included. The α- and β-anomers of 7-chloro-3-(2-deoxy-D-erythro-pentofuranosyl)-3H-1,2,3-triazolo[4,5-b]pyridine (3a and 4) showed activities against Sb-1 and Coxs viruses. The α- and β-anomers of 2′,3′-dideoxy-8-aza-1-deazaadenosine (20 and 21) were found active as inhibitors ...

A new facile synthesis and antiviral activity of oxazofurin

Abstract A new, more facile synthesis of oxazofurin, a structural analogue of tiazofurin, selenazofurin and ribavirin, has been carried out by rhodium catalyzed reaction of ethyl α-formyl-diazoacetate with 2,3, 5-tri-O-benzoyl-β-D-ribofu-ranosyl cyanide. When evaluated against DNA and RNA viruses, HIV-1 inclu-ded, oxazofurin was found inactive. It was also ineffective in potentiating the anti-HIV activity of 2′, 3′-dideoxyadenosine.

Synthesis, antitumor activity and crystallographic studies of analogues of tiazofurin

Abstract The syntheses and antitumor activity of 2-β-D-ribofuranosylfuran-4-carboxamide (furanfurin) and 2-β-D-ribofuranosylthiophene-4-carboxamide (thiophenfurin) are reported. The X-ray structure of ethyl 2-β-D-ribofuranosylthiophene-4-carboxylate, precursor of thiophenfurin, is also presented. Only thiophenfurin showed activity as an antitumor agent both in vitro and in vivo.