| Literature DB >> 22658862 |
Dinesh A Barawkar1, Anish Bandyopadhyay, Anil Deshpande, Summon Koul, Sachin Kandalkar, Pradeep Patil, Goraksha Khose, Samir Vyas, Mahesh Mone, Shubhangi Bhosale, Umesh Singh, Siddhartha De, Ashwin Meru, Jayasagar Gundu, Anita Chugh, Venkata P Palle, Kasim A Mookhtiar, Joseph P Vacca, Prasun K Chakravarty, Ravi P Nargund, Samuel D Wright, Sophie Roy, Michael P Graziano, Doris Cully, Tian-Quan Cai, Sheo B Singh.
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.Entities:
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Year: 2012 PMID： 22658862 DOI： 10.1016/j.bmcl.2012.05.020
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823