Format

Send to

Choose Destination
See comment in PubMed Commons below
Bioorg Med Chem Lett. 2009 Jan 1;19(1):222-5. doi: 10.1016/j.bmcl.2008.10.107. Epub 2008 Oct 31.

Design and synthesis of pyrazole derivatives as potent and selective inhibitors of tissue-nonspecific alkaline phosphatase (TNAP).

Author information

1
Burnham Center for Chemical Genomics, Burnham Institute for Medical Research, La Jolla, CA 92037, USA.

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.

PMID:
19038545
PMCID:
PMC2752324
DOI:
10.1016/j.bmcl.2008.10.107
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center