9-[2-(Phosphonomethoxy)ethyl]adenine (PMEA) and 9-[2-(Phosphonomethoxy)ethyl]guanine (PMEG) are potent and selective inhibitors of a broad-sprectrum of DNA viruses and retroviruses, including human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) in vitro and in vivo. We report here on the syntheses of 8-aza-analogues of such acyclic nucleotides. 9-Phosphonomethoxyethylation of 8-azaadenine and 8-azaguanine with 2-[1-(diethylphosphonomethoxyethyl] p-toluensulfonate in DMF in the presence of sodium hydride, gave a mixture of regioisomers which were separated and readily distinguished by spectroscopic data. Deprotection of the phosphonate esters with TMSBr gave the desired compounds. In vitro antiviral activities of the title compounds will be reported and discussed.
Synthesis and in vivo antiviral activity of 8-aza-analogues of potent antiviral agents 9-[2-phosphonomethoxy)ethyl]adenine (PMEA) and 9-[2-phosphonomethoxy)ethyl]guanine (PMEG)
FRANCHETTI, Palmarisa;CAPPELLACCI, Loredana;GRIFANTINI, Mario;
1993-01-01
Abstract
9-[2-(Phosphonomethoxy)ethyl]adenine (PMEA) and 9-[2-(Phosphonomethoxy)ethyl]guanine (PMEG) are potent and selective inhibitors of a broad-sprectrum of DNA viruses and retroviruses, including human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) in vitro and in vivo. We report here on the syntheses of 8-aza-analogues of such acyclic nucleotides. 9-Phosphonomethoxyethylation of 8-azaadenine and 8-azaguanine with 2-[1-(diethylphosphonomethoxyethyl] p-toluensulfonate in DMF in the presence of sodium hydride, gave a mixture of regioisomers which were separated and readily distinguished by spectroscopic data. Deprotection of the phosphonate esters with TMSBr gave the desired compounds. In vitro antiviral activities of the title compounds will be reported and discussed.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
