| Autor: |
Michael P. Graziano, Anish Bandyopadhyay, Goraksha Khose, Chandrasekhar Koduru, Venkata P. Palle, Doris F. Cully, Sophie Roy, Sanjay Niranjan, Anil M. Deshpande, Pradeep Rangrao Patil, Prasun K. Chakravarty, Ashwin Meru, Shubhangi Bhosale, Sachin Kandalkar, Ravi P. Nargund, Koshu Mahajan, Chandrashekhar Athare, Sheo B. Singh, Anita Chugh, Abir L. Banerjee, Joseph P. Vacca, Umesh Prasad Singh, Siddhartha De, Sudit S. Mukhopadhyay, Tian-Quan Cai, Sumit Chaudhary, Kasim A. Mookhtiar, Jayasagar Gundu, Samuel D. Wright, Dinesh A. Barawkar, Summon Koul |
| Rok vydání: |
2011 |
| Předmět: |
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| Zdroj: |
ACS medicinal chemistry letters. 2(12) |
| ISSN: |
1948-5875 |
| Popis: |
l-2-Hydroxy acid oxidase (Hao2) is a peroxisomal enzyme with predominant expression in the liver and kidney. Hao2 was recently identified as a candidate gene for blood pressure quantitative trait locus in rats. To investigate a pharmacological role of Hao2 in the management of blood pressure, selective Hao2 inhibitors were developed. Optimization of screening hits 1 and 2 led to the discovery of compounds 3 and 4 as potent and selective rat Hao2 inhibitors with pharmacokinetic properties suitable for in vivo studies in rats. Treatment with compound 3 or 4 resulted in a significant reduction or attenuation of blood pressure in an established or developing model of hypertension, deoxycorticosterone acetate-treated rats. This is the first report demonstrating a pharmacological benefit of selective Hao2 inhibitors in a relevant model of hypertension. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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