Design and synthesis of pyrazole derivatives as potent and selective inhibitors of tissue-nonspecific alkaline phosphatase (TNAP).
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ABSTRACT:
SUBMITTER: Sidique S
PROVIDER: S-EPMC2752324 | biostudies-literature | 2009 Jan
REPOSITORIES: biostudies-literature
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Design and synthesis of pyrazole derivatives as potent and selective inhibitors of tissue-nonspecific alkaline phosphatase (TNAP).
Sidique Shyama S Ardecky Robert R Su Ying Y Narisawa Sonoko S Brown Brock B Millán José Luis JL Sergienko Eduard E Cosford Nicholas D P ND
Bioorganic & medicinal chemistry letters 20081031 1
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 ser ...[more]
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