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Synthesis and evaluation of thiophenyl derivatives as inhibitors of alkaline phosphatase |
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| Authors: | Chang Lei Duy Do Le Mébarek Saida Popowycz Florence Pellet-Rostaing Stéphane Lemaire Marc Buchet René |
| Institution: | a Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, UMR-CNRS 5246, Equipe Catalyse Synthèse Environnement, Université de Lyon, Université Claude Bernard-Lyon 1, Bâtiment Curien, 43 Bd du 11 Novembre 1918, F-69622 Villeurbanne, France b Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, UMR-CNRS 5246, Equipe Organisation et Dynamique des Membranes Biologiques, Université de Lyon, Université Claude Bernard-Lyon 1, Bâtiment Raulin, 43 Bd du 11 Novembre 1918, F-69622 Villeurbanne, France c Institut de Chimie Séparative de Marcoule, UMR-CNRS 5257, Site de Marcoule, Université Montpellier 2, F-30207 Bagnols sur Cèze, France |
| Abstract: | Pathological calcifications induced by deposition of basic phosphate crystals or hydroxyapatite (HA) on soft tissues are a large family of diseases comprising of ankylosing spondylitis (AS), end-stage osteoarthritis (OA) and vascular calcification. High activity of tissue non-specific alkaline phosphatase (TNAP) is a hallmark of pathological calcifications induced by HA deposition. The use of TNAP inhibitor is a possible therapeutic option to address calcific diseases produced by HA deposition on soft tissues. We report the synthesis of a series of thiopheno-imidazo2,1-b]thiazole derivatives which were evaluated as potential inhibitors of TNAP displaying a large range of IC50 at pH 10.4 (from 42 ± 13 μM to more than 800 μM). |
| Keywords: | Thiophene Alkaline phosphatase Inhibitor Calcification disease |
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