Potent inhibitors of HCV-NS3 protease derived from boronic acids
Chronic hepatitis C infection is the leading causes for cirrhosis of the liver and hepatocellular carcinoma, leading to liver failure and liver transplantation. The etiological agent, HCV virus produces a single positive strand of RNA that is processed with the help of serine protease NS3 to produce...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2009-01, Vol.19 (1), p.180-183 |
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| creator | Venkatraman, Srikanth Wu, Wanli Prongay, Andrew Girijavallabhan, Viyyoor George Njoroge, F. |
| description | Chronic hepatitis C infection is the leading causes for cirrhosis of the liver and hepatocellular carcinoma, leading to liver failure and liver transplantation. The etiological agent, HCV virus produces a single positive strand of RNA that is processed with the help of serine protease NS3 to produce mature virus. Inhibition of NS3 protease can be potentially used to develop effective drugs for HCV infections. Numerous efforts are now underway to develop potent inhibitors of HCV protease that contain ketoamides as serine traps. Herein we report the synthesis of a series of potent inhibitors that contain a boronic acid as a serine trap. The activity of these compounds were optimized to 200
pM. X-ray structure of compound
17 bound to NS3 protease is also discussed. |
| doi_str_mv | 10.1016/j.bmcl.2008.10.124 |
| format | Article |
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pM. X-ray structure of compound
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Drug treatments</subject><subject>Protease Inhibitors - chemical synthesis</subject><subject>Protease Inhibitors - pharmacology</subject><subject>RNA</subject><subject>SERINE</subject><subject>SYNTHESIS</subject><subject>Viral Nonstructural Proteins - antagonists & inhibitors</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU1rFEEQhpsQMWv0D3iQIaC32VR_zgx4SFjUCMEIfpBb0x81pJeZ6aR7NuC_t8dd9Kaemq56qniph5CXFNYUqDrfru3ohjUDaNdLjYkjsqJCiZoLkMdkBZ2Cuu3E7Ql5lvMWgAoQ4ik5oR0wphpYkYvPccZprsJ0F2yYY8pV7Kurzff60xde3afSNRkrjyk8oq_6FMfKxhSn4Crjgs_PyZPeDBlfHN5T8u39u6-bq_r65sPHzeV17STv5tqqjremlYC-azq0XjALLVqlWtPzvgVJG2Vl-Yiee-s5emkc5YaBaJRi_JSc7ffGPAedXZjR3bk4TehmTQFkw2SB3uyhEvxhh3nWY8gOh8FMGHdZK9U0ALz7J8iACwUS_gNkSlAhCsj2oEsx54S9vk9hNOlHCacXXXqrF1160fWrxpahV4ftOzui_zNy8FOA1wfAZGeGPpnJhfybYxQ4UNoU7u2ew6LgMWBaLoSTQx_SciAfw99y_AT0yLCT</recordid><startdate>20090101</startdate><enddate>20090101</enddate><creator>Venkatraman, Srikanth</creator><creator>Wu, Wanli</creator><creator>Prongay, Andrew</creator><creator>Girijavallabhan, Viyyoor</creator><creator>George Njoroge, F.</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope><scope>OTOTI</scope></search><sort><creationdate>20090101</creationdate><title>Potent inhibitors of HCV-NS3 protease derived from boronic acids</title><author>Venkatraman, Srikanth ; Wu, Wanli ; Prongay, Andrew ; Girijavallabhan, Viyyoor ; George Njoroge, F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c539t-b6938a850ed979ebd42b08eb668af3f805176b58af4f3dbd3ed5ac13a20476623</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Amides - chemical synthesis</topic><topic>Amides - pharmacology</topic><topic>Antibiotics. 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| subjects | Amides - chemical synthesis Amides - pharmacology Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral agents Antiviral Agents - chemical synthesis Antiviral Agents - pharmacology BASIC BIOLOGICAL SCIENCES Biological and medical sciences Boronic acid BORONIC ACIDS Boronic Acids - chemical synthesis Boronic Acids - pharmacology Crystallography, X-Ray GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE HCV HEPATITIS Hepatitis C virus LIVER Medical sciences Molecular Structure NS3 protease Pharmacology. Drug treatments Protease Inhibitors - chemical synthesis Protease Inhibitors - pharmacology RNA SERINE SYNTHESIS Viral Nonstructural Proteins - antagonists & inhibitors |
| title | Potent inhibitors of HCV-NS3 protease derived from boronic acids |
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