2 `-O-Alkyl Derivatives and 5 `-Analogues of 5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) as Potential Hsp90 Inhibitors

Some selective preparations of AICAR-related compounds modified at the 2'- or 5'-position of the ribose moiety are reported herein. In particular, 5'-azido, 5'-amino, 5'-O-benzyl and a series of 2'-O-alkylated AICAR derivatives have been synthesized. These compounds were derived from appropriately functionalized inosines by opening the pyrimidine ring at the hypoxanthine residue. The target derivatives were designed with the purpose of studying the effect of AICAR structural modifications on its ability to inhibit Hsp90, one of the biological targets for the development of anticancer agents. Nevertheless, the development of AICAR-like compounds is an appealing objective also because of their potential therapeutic application in the field of metabolic studies. ((C) Wiley-VCH Verlag GmbH \& Co. KGaA, 69451 Weinheim, Germany, 2009)