Flow Synthesis and Biological Studies of an Analgesic Adamantane Derivative That Inhibits P2X7‐Evoked Glutamate Release

Battilocchio, C; Guetzoyan, L; Cervetto, C; Di Cesare Mannelli, Lorenzo; Frattaroli, D; Baxendale, Ir; Maura, G; Rossi, A; Sautebin, L; Biava, M; Ghelardini, Carla; Marcoli, M; Ley, Sv

doi:10.1021/ml400079h

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. KEYWORDS: Adamantane derivatives, 2-aminoadamantane-2-carboxylic acid, analgesic agents, flow chemistry, purinergic receptors

Flow Synthesis and Biological Studies of an Analgesic Adamantane Derivative That Inhibits P2X7‐Evoked Glutamate Release / Battilocchio C, Guetzoyan L, Cervetto C, Di Cesare Mannelli L, Frattaroli D, Baxendale IR, Maura G, Rossi A, Sautebin L, Biava M, Ghelardini C, Marcoli M, Ley SV. - In: ACS MEDICINAL CHEMISTRY LETTERS. - ISSN 1948-5875. - STAMPA. - 4:(2013), pp. 704-709. [10.1021/ml400079h]