title: Flow Synthesis and Biological Studies of an Analgesic Adamantane Derivative That Inhibits P2X7-Evoked Glutamate Release.
abstract: We report the biological evaluation of a class of adamantane derivatives, which were achieved via modified telescoped machine-assisted flow procedure. Among the series of compounds tested in this work, 5 demonstrated outstanding analgesic properties. This compound showed that its action was not mediated through direct interaction with opioid and/or cannabinoid receptors. Moreover, it did not display any significant anti-inflammatory properties. Experiments carried out on rat cerebrocortical purified synaptosomes indicated that 5 inhibits the P2X7-evoked glutamate release, which may contribute to its antinociceptive properties. Nevertheless, further experiments are ongoing to characterize the pharmacological properties and mechanism of action of this molecule.
authors.affiliation: Innovative Technology Centre, Department of Chemistry, University of Cambridge , Lensfield Road, CB2 1EW, United Kingdom.
authors.forename: Claudio
authors.initials: C
authors.lastname: Battilocchio
authors.affiliation: Innovative Technology Centre, Department of Chemistry, University of Cambridge , Lensfield Road, CB2 1EW, United Kingdom.
authors.forename: Lucie
authors.initials: L
authors.lastname: Guetzoyan
authors.affiliation: Dipartimento di Farmacia, Sezione di Farmacologia e Tossicologia, Universita'di Genova , Viale Cembrano 4, 16148 Genova, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Cervetto
authors.affiliation: Dipartimento di Neuroscienze, Psicologia Area del Farmaco e Salute del Bambino, Universita' di Firenze , Viale G. Pieraccini 6, 50139 Firenze, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Di Cesare Mannelli
authors.affiliation: Dipartimento di Farmacia, Sezione di Farmacologia e Tossicologia, Universita'di Genova , Viale Cembrano 4, 16148 Genova, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Frattaroli
authors.affiliation: Department of Chemistry, Durham University , South Road, DH1 3LE Durham, United Kingdom.
authors.forename: Ian R
authors.initials: IR
authors.lastname: Baxendale
authors.affiliation: Dipartimento di Farmacia, Sezione di Farmacologia e Tossicologia, Universita'di Genova , Viale Cembrano 4, 16148 Genova, Italy ; Center of Excellence for Biomedical Research, Universita' di Genova , Viale Benedetto XV 5, 16132 Genova, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Maura
authors.affiliation: Dipartimento di Farmacologia Sperimentale, Universita' di Napoli "Federico II" , Via D. Montesano 49, 80131 Napoli, Italy.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Rossi
authors.affiliation: Dipartimento di Farmacologia Sperimentale, Universita' di Napoli "Federico II" , Via D. Montesano 49, 80131 Napoli, Italy.
authors.forename: Lidia
authors.initials: L
authors.lastname: Sautebin
authors.affiliation: Dipartmento di Chimica e Tecnologie del Farmaco, Sapienza Universita' di Roma , P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Biava
authors.affiliation: Dipartimento di Neuroscienze, Psicologia Area del Farmaco e Salute del Bambino, Universita' di Firenze , Viale G. Pieraccini 6, 50139 Firenze, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Ghelardini
authors.affiliation: Dipartimento di Farmacia, Sezione di Farmacologia e Tossicologia, Universita'di Genova , Viale Cembrano 4, 16148 Genova, Italy ; Center of Excellence for Biomedical Research, Universita' di Genova , Viale Benedetto XV 5, 16132 Genova, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Marcoli
authors.affiliation: Innovative Technology Centre, Department of Chemistry, University of Cambridge , Lensfield Road, CB2 1EW, United Kingdom.
authors.forename: Steven V
authors.initials: SV
authors.lastname: Ley
keywords: 2-aminoadamantane-2-carboxylic acid; Adamantane derivatives; analgesic agents; flow chemistry; purinergic receptors