title: Design and synthesis of N-benzylpiperidine-purine derivatives as new dual inhibitors of acetyl- and butyrylcholinesterase.
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 acetylcholinesterase 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.
authors.affiliation: Instituto de Química Médica (C.S.I.C.), Juan de la Cierva 3, 28006 Madrid, Spain. isabelrguez@iqm.csic.es
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Rodríguez-Franco
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Fernández-Bachiller
authors.forename: Concepción
authors.initials: C
authors.lastname: Pérez
authors.forename: Ana
authors.initials: A
authors.lastname: Castro
authors.forename: Ana
authors.initials: A
authors.lastname: Martínez
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002417:Cattle; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D006736:Horses; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011687:Purines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D002800:Cholinesterase Inhibitors; C507118:N-benzylpiperidine-purine; D010880:Piperidines; D011687:Purines; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; C030985:purine