Patent Evaluation Biologicals & Immunologicals: 6-Oxo-nucleosides with immunosuppressant activity

Abstract

This patent describes the use and preparation of 6-oxo-nucleosides as immunosuppressants, which may have utility in treating patients for transplant rejection or autoimmune diseases. Compounds having the formula 1 and their preparation are described.

The compounds, which are T-cell selective immunosuppressive agents, are similar to compounds previously ascribed to the category of purine nucleoside phosphorylase (PNP) inhibitors. This is an abundantly researched area and several reviews have been written [1]. Marion Merrell Dow appears to have dominated the area in terms of patent activity and has previously patented the preparation of carbocyclic adenosine nucleosides [101], and 5-fluorouridine 9-N-bicyclic nucleoside derivatives [102], among others. Parke-Davis Pharmaceuticals/Warner-Lambert Co. has also been active and has patented 9-substituted-8-halo or 8-hydroxy-9-deazaguanines [103], whereas Burroughs Wellcome has recently disclosed a series of 2-deoxyribofuranosyl imidazopyridine derivatives [104]. Other compounds that have been described in the literature include alkylthio, arylthio and thiocyanato purines [2].