Non-nucleoside adenosine deaminase inhibitors: 2000-2004

Adenosine deaminase (ADA) is a crucial enzyme in purine metabolism that irreversibly deaminates adenosine to form inosine. ADA is ubiquitous in human tissues and plays a crucial role in immune system development. ADA inhibitors may be useful for the treatment of ischaemic injury, hypertension, lymphomas and leukaemia. Furthermore, ADA inhibitors have recently also been considered as anti-inflammatory drugs. Most ADA inhibitors to date are purine nucleosides or alkyladenine analogues that have poor pharmacokinetics and/or several toxicities. ADA inhibitors without these problems may improve the treatment of leukaemia and also have potential for use in many other clinical conditions. This hypothesis has generated considerable interest in the development of non-nucleoside ADA inhibitors. Recently, a Fujisawa non-nucleoside ADA inhibitor demonstrated in vivo efficacy in inflammation and lymphoma models after oral administration. This review describes recent advances in the development of non-nucleoside ADA inhibitors, based on the patent literature from January 2000 to December 2004.