The introduction of the isoxazole ring as bioisosteric replacement of the acetyl group of anatoxin-a led to a new series of derivatives binding to nicotinic acetylcholine receptors. Bulkier substitutions than methyl at the 3 position of isoxazole were shown to be detrimental for the activity. The binding potency of the most interesting compounds with alpha 1, alpha 7 and alpha 3 beta 4 receptor subtypes, was, anyway, only at micromolar level. Moreover, differently from known derivatives with pyridine, isoxazole condensed to azabicyclo ring led to no activity. (C) 2011 Elsevier Ltd. All rights reserved.
Synthesis and biological activity of a novel class nicotinic acetylcholine receptors (nAChRs) ligands structurally related to anatoxin-a / Daniele, Simoni; Riccardo, Rondanin; Marchetti, Paolo; Cinzia, Rullo; Riccardo, Baruchello; Giuseppina, Grisolia; Giuseppina, Barbato; Riccardo, Giovannini; Carla, Marchioro; Anna Maria, Capelli; Caterina, Virginio; Andrea, Bozzoli; Pier Andrea, Borea; Stefania, Merighi; Daniele, Donati. - In: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - 21:18(2011), pp. 5423-5427. [10.1016/j.bmcl.2011.06.127]
Synthesis and biological activity of a novel class nicotinic acetylcholine receptors (nAChRs) ligands structurally related to anatoxin-a
MARCHETTI, PAOLO;
2011
Abstract
The introduction of the isoxazole ring as bioisosteric replacement of the acetyl group of anatoxin-a led to a new series of derivatives binding to nicotinic acetylcholine receptors. Bulkier substitutions than methyl at the 3 position of isoxazole were shown to be detrimental for the activity. The binding potency of the most interesting compounds with alpha 1, alpha 7 and alpha 3 beta 4 receptor subtypes, was, anyway, only at micromolar level. Moreover, differently from known derivatives with pyridine, isoxazole condensed to azabicyclo ring led to no activity. (C) 2011 Elsevier Ltd. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
