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ID: ALA1139306
Journal: Bioorg Med Chem Lett
Title: Design and synthesis of pyrazole derivatives as potent and selective inhibitors of tissue-nonspecific alkaline phosphatase (TNAP).
Authors: Sidique S, Ardecky R, Su Y, Narisawa S, Brown B, Millán JL, Sergienko E, Cosford ND.
Abstract: Tissue-nonspecific alkaline phosphatase (TNAP) plays a central role in regulating extracellular matrix calcification during bone formation and growth. High-throughput screening (HTS) for small molecule TNAP inhibitors led to the identification of hits in the sub-micromolar potency range. We report the design, synthesis and in vitro evaluation of a series of pyrazole derivatives of a screening hit which are potent TNAP inhibitors exhibiting IC(50) values as low as 5nM. A representative of the series was characterized in kinetic studies and determined to have a mode of inhibition not previously observed for TNAP inhibitors.
CiteXplore: 19038545