Synthesis and biological evaluation of clitocine analogues as adenosine kinase inhibitors

Adenosine kinase (AK) is the primary enzyme responsible for adenosine metab olism. Inhibition of AK effectively increases extracellular adenosine conce ntrations and represents an alternative approach to enhance the beneficial actions of adenosine as compared to direct-acting receptor agonists. Clitoc ine (3), isolated from the mushroom Clitocybe inversa, has been found to be a weak inhibitor of AK. We have prepared a number of analogues of clitocin e in order to improve its potency and demonstrated that 5 ' -deoxy-5 ' -ami no-clitocine (7) improved AK inhibitory potency by 50-fold. (C) 2001 Elsevi er Science Ltd. All rights reserved.