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Bioorg Med Chem Lett. 2012 Jul 1;22(13):4341-7. doi: 10.1016/j.bmcl.2012.05.020. Epub 2012 May 11.

Discovery of pyrazole carboxylic acids as potent inhibitors of rat long chain L-2-hydroxy acid oxidase.

Author information

  • 1Drug Discovery Facility, Advinus Therapeutics, Quantum Towers, Plot-9, Phase-I, Rajiv Gandhi InfoTech Park, Hinjewadi, Pune 411 057, India. dinesh.barawkar@advinus.com

Abstract

Long chain L-2-hydroxy acid oxidase 2 (Hao2) is a peroxisomal enzyme expressed in the kidney and the liver. Hao2 was identified as a candidate gene for blood pressure (BP) quantitative trait locus (QTL) but the identity of its physiological substrate and its role in vivo remains largely unknown. To define a pharmacological role of this gene product, we report the development of selective inhibitors of Hao2. We identified pyrazole carboxylic acid hits 1 and 2 from screening of a compound library. Lead optimization of these hits led to the discovery of 15-XV and 15-XXXII as potent and selective inhibitors of rat Hao2. This report details the structure activity relationship of the pyrazole carboxylic acids as specific inhibitors of Hao2.

Copyright © 2012 Elsevier Ltd. All rights reserved.

PMID:
22658862
[PubMed - indexed for MEDLINE]
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