Novel nucleoside analogues of both D and L enantiomeric series were prepared by coupling reaction between a 2',3'-dideoxy-3'-modified furanose moiety and four different nucleobases. Though in all cases anomeric mixtures of nucleosides were obtained, the presence of the sterically bulky 3-tris(methylthio)methyl group allowed a good stereo selectivity level. All the compounds of both enantiomeric series showed high IC50 values as HSV-1 TK inhibitors and scarce ability to be phosphorylated by HSV-1 TK. In order to overcome possible problems related to the first phosphorylation step and to facilitate the penetration of the molecule through the cellular membrane, a monophosphate prodrug containing a long lipophilic chain was synthesized. No appreciable antiviral activity was exhibited by this molecule. (C) 2002 Elsevier Science Ltd. All rights reserved.
Mugnaini, C., Botta, M., Coletta, M., Corelli, F., Focher, F., Marini, S., et al. (2003). Research on L-nucleosides. Synthesis and biological evaluation of a series of L- and D-2 ',3 '-Dideoxv-3 '-[tris(methylthio)methyl]beta-pentofuranosyl nucleosides. BIOORGANIC & MEDICINAL CHEMISTRY, 11(3), 357-366 [10.1016/S0968-0896(02)00460-1].
Research on L-nucleosides. Synthesis and biological evaluation of a series of L- and D-2 ',3 '-Dideoxv-3 '-[tris(methylthio)methyl]beta-pentofuranosyl nucleosides
COLETTA, MASSIMILIANO;MARINI, STEFANO;
2003-01-01
Abstract
Novel nucleoside analogues of both D and L enantiomeric series were prepared by coupling reaction between a 2',3'-dideoxy-3'-modified furanose moiety and four different nucleobases. Though in all cases anomeric mixtures of nucleosides were obtained, the presence of the sterically bulky 3-tris(methylthio)methyl group allowed a good stereo selectivity level. All the compounds of both enantiomeric series showed high IC50 values as HSV-1 TK inhibitors and scarce ability to be phosphorylated by HSV-1 TK. In order to overcome possible problems related to the first phosphorylation step and to facilitate the penetration of the molecule through the cellular membrane, a monophosphate prodrug containing a long lipophilic chain was synthesized. No appreciable antiviral activity was exhibited by this molecule. (C) 2002 Elsevier Science Ltd. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
