Design, synthesis and antiproliferative activity of methyl 4-iodo-1-b-D-ribofuranosyl-pyrazole-3-carboxylate and related compounds

Continuing our studies on the structure-activity relationships of some pyrazole nucleosides (1a-h) structurally related to ribavirin, tiazofurin and selenazofurin, we describe here the synthesis and antitumor/antiviral/antimicrobial activity of a new series of 1-tetrahydropyranyl-4-substituted pyrazoles. In this study, the tetrahydropyranyl moiety (THP), designed as a mimic of the glycosidic portion of the parent compounds 1a-h, has led to a few derivatives with moderate cytotoxic activity against leukemia/lymphoma and solid tumor-derived cell lines (IC50 14-100 microM). The compounds obtained through substitution of the ribofuranosyl moiety by the THP moiety were still active, the free heterocyclic bases were devoid of any activity.

In a SAR study on azole-related nucleosides we have designed some pyrazole-nucleoside analogs characterised, for the first time, by a carboxylic ester moiety. 4-Iodo-1-β-D-ribofuranosyl-pyrazole-3-carboxylate showed a wide spectrum of antiproliferative activity and a particularly low cytotoxicity against resting PBL, being, unlike the other azole nucleosides, more active than the corresponding primary amide. Copyright © 1996 Elsevier Science Ltd.