Dinesh A Barawkar,
Anish Bandyopadhyay,
Anil Deshpande,
Summon Koul,
Sachin Kandalkar,
Pradeep Patil, Goraksha Khose,
Samir Vyas,
Mahesh Mone,
Shubhangi Bhosale, [......],
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
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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.
Bioorganic & medicinal chemistry letters 05/2012; 22(13):4341-7. · 2.65 Impact Factor
