Abstract

The synthesis and biological evaluation of N-benzyl-(piperidin or pyrrolidin)-purines are described. Compounds derived from N-benzylpiperidine and N-substituted purines showed moderate acetyleholinesterase inhibition. Preliminary structure-activity relationships and a superimposition of the best compound with the active conformation of donepezil have revealed structural features that have been used in the design of more potent N-benzylpiperidine inhibitors bearing an 8-substituted caffeine fragment and a methoxymethyl linker. These new compounds are interesting dual inhibitors of acetylcholinesterase and butyrylcholinesterase and have been chosen for further optimisation. (c) 2005 Elsevier Ltd. All rights reserved.