title: Synthesis and evaluation of thiophenyl derivatives as inhibitors of alkaline phosphatase.
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-imidazo[2,1-b]thiazole derivatives which were evaluated as potential inhibitors of TNAP displaying a large range of IC(50) at pH 10.4 (from 42±13 μM to more than 800 μM).
authors.affiliation: Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, UMR-CNRS 5246, Equipe Catalyse Synthèse Environnement, Université Claude Bernard-Lyon 1, Bâtiment Curien, 43 Bd du 11 Novembre 1918, F-69622 Villeurbanne, France.
authors.forename: Lei
authors.initials: L
authors.lastname: Chang
authors.forename: Do Le
authors.initials: do L
authors.lastname: Duy
authors.forename: Saida
authors.initials: S
authors.lastname: Mébarek
authors.forename: Florence
authors.initials: F
authors.lastname: Popowycz
authors.forename: Stéphane
authors.initials: S
authors.lastname: Pellet-Rostaing
authors.forename: Marc
authors.initials: M
authors.lastname: Lemaire
authors.forename: René
authors.initials: R
authors.lastname: Buchet
mesh_terms: D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002114:Calcinosis / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010636:Phenols / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D004791:Enzyme Inhibitors; D010636:Phenols; D013438:Sulfhydryl Compounds; D013844:Thiazoles; C042983:thiophenol; D000469:Alkaline Phosphatase