Discovery of GS-9256: A novel phosphinic acid derived inhibitor of the hepatitis C virus NS3/4A protease with potent clinical activity
A potent and novel class of phosphinic acid derived product-like inhibitors of the HCV NS3/4A protease was discovered previously. Modification of the phosphinic acid and quinoline heterocycle led to GS-9256 with potent cell-based activity and favorable pharmacokinetic parameters. Based on these attr...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2012-02, Vol.22 (3), p.1394-1396 |
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| container_title | Bioorganic & medicinal chemistry letters |
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| creator | Sheng, X. Christopher Casarez, Anthony Cai, Ruby Clarke, Michael O. Chen, Xiaowu Cho, Aesop Delaney, William E. Doerffler, Edward Ji, Mingzhe Mertzman, Michael Pakdaman, Rowchanak Pyun, Hyung-Jung Rowe, Tanisha Wu, Qiaoyin Xu, Jie Kim, Choung U. |
| description | A potent and novel class of phosphinic acid derived product-like inhibitors of the HCV NS3/4A protease was discovered previously. Modification of the phosphinic acid and quinoline heterocycle led to GS-9256 with potent cell-based activity and favorable pharmacokinetic parameters. Based on these attributes, GS-9256 was advanced to human clinical trial as a treatment for chronic infection with genotype 1 HCV. |
| doi_str_mv | 10.1016/j.bmcl.2011.12.038 |
| format | Article |
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Christopher ; Casarez, Anthony ; Cai, Ruby ; Clarke, Michael O. ; Chen, Xiaowu ; Cho, Aesop ; Delaney, William E. ; Doerffler, Edward ; Ji, Mingzhe ; Mertzman, Michael ; Pakdaman, Rowchanak ; Pyun, Hyung-Jung ; Rowe, Tanisha ; Wu, Qiaoyin ; Xu, Jie ; Kim, Choung U.</creator><creatorcontrib>Sheng, X. Christopher ; Casarez, Anthony ; Cai, Ruby ; Clarke, Michael O. ; Chen, Xiaowu ; Cho, Aesop ; Delaney, William E. ; Doerffler, Edward ; Ji, Mingzhe ; Mertzman, Michael ; Pakdaman, Rowchanak ; Pyun, Hyung-Jung ; Rowe, Tanisha ; Wu, Qiaoyin ; Xu, Jie ; Kim, Choung U.</creatorcontrib><description>A potent and novel class of phosphinic acid derived product-like inhibitors of the HCV NS3/4A protease was discovered previously. Modification of the phosphinic acid and quinoline heterocycle led to GS-9256 with potent cell-based activity and favorable pharmacokinetic parameters. Based on these attributes, GS-9256 was advanced to human clinical trial as a treatment for chronic infection with genotype 1 HCV.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2011.12.038</identifier><identifier>PMID: 22244938</identifier><language>eng</language><publisher>Amsterdam: Elsevier Ltd</publisher><subject>Animals ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antiviral agents ; Biological and medical sciences ; Carboxylate isostere ; Carrier Proteins - antagonists & inhibitors ; Chronic infection ; Clinical trials ; Dogs ; Drug Discovery ; Enzyme Inhibitors - chemical synthesis ; Enzyme Inhibitors - chemistry ; Enzyme Inhibitors - pharmacology ; genotype ; Genotypes ; GS-9256 ; HCV ; Hepacivirus - drug effects ; Hepacivirus - enzymology ; Hepatitis C virus ; Humans ; Inhibitory Concentration 50 ; Medical sciences ; Molecular Structure ; NS3/4A protease inhibitor ; Peptides, Cyclic - chemical synthesis ; Peptides, Cyclic - chemistry ; Peptides, Cyclic - pharmacology ; Pharmacokinetics ; Pharmacology. Drug treatments ; Phosphinic acid ; Phosphinic Acids - chemical synthesis ; Phosphinic Acids - chemistry ; Phosphinic Acids - pharmacology ; Proteinase ; proteinases ; quinoline ; Quinolines ; Swine ; Viral Nonstructural Proteins - antagonists & inhibitors</subject><ispartof>Bioorganic & medicinal chemistry letters, 2012-02, Vol.22 (3), p.1394-1396</ispartof><rights>2011</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011. Published by Elsevier Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c442t-cce2970a4566c2b96462a2a19b3ac5d18e53c780ff9354ffbc43c666420592a33</citedby><cites>FETCH-LOGICAL-c442t-cce2970a4566c2b96462a2a19b3ac5d18e53c780ff9354ffbc43c666420592a33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bmcl.2011.12.038$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,45974</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25476095$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22244938$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sheng, X. Christopher</creatorcontrib><creatorcontrib>Casarez, Anthony</creatorcontrib><creatorcontrib>Cai, Ruby</creatorcontrib><creatorcontrib>Clarke, Michael O.</creatorcontrib><creatorcontrib>Chen, Xiaowu</creatorcontrib><creatorcontrib>Cho, Aesop</creatorcontrib><creatorcontrib>Delaney, William E.</creatorcontrib><creatorcontrib>Doerffler, Edward</creatorcontrib><creatorcontrib>Ji, Mingzhe</creatorcontrib><creatorcontrib>Mertzman, Michael</creatorcontrib><creatorcontrib>Pakdaman, Rowchanak</creatorcontrib><creatorcontrib>Pyun, Hyung-Jung</creatorcontrib><creatorcontrib>Rowe, Tanisha</creatorcontrib><creatorcontrib>Wu, Qiaoyin</creatorcontrib><creatorcontrib>Xu, Jie</creatorcontrib><creatorcontrib>Kim, Choung U.</creatorcontrib><title>Discovery of GS-9256: A novel phosphinic acid derived inhibitor of the hepatitis C virus NS3/4A protease with potent clinical activity</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>A potent and novel class of phosphinic acid derived product-like inhibitors of the HCV NS3/4A protease was discovered previously. Modification of the phosphinic acid and quinoline heterocycle led to GS-9256 with potent cell-based activity and favorable pharmacokinetic parameters. Based on these attributes, GS-9256 was advanced to human clinical trial as a treatment for chronic infection with genotype 1 HCV.</description><subject>Animals</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antiviral agents</subject><subject>Biological and medical sciences</subject><subject>Carboxylate isostere</subject><subject>Carrier Proteins - antagonists & inhibitors</subject><subject>Chronic infection</subject><subject>Clinical trials</subject><subject>Dogs</subject><subject>Drug Discovery</subject><subject>Enzyme Inhibitors - chemical synthesis</subject><subject>Enzyme Inhibitors - chemistry</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>genotype</subject><subject>Genotypes</subject><subject>GS-9256</subject><subject>HCV</subject><subject>Hepacivirus - drug effects</subject><subject>Hepacivirus - enzymology</subject><subject>Hepatitis C virus</subject><subject>Humans</subject><subject>Inhibitory Concentration 50</subject><subject>Medical sciences</subject><subject>Molecular Structure</subject><subject>NS3/4A protease inhibitor</subject><subject>Peptides, Cyclic - chemical synthesis</subject><subject>Peptides, Cyclic - chemistry</subject><subject>Peptides, Cyclic - pharmacology</subject><subject>Pharmacokinetics</subject><subject>Pharmacology. Drug treatments</subject><subject>Phosphinic acid</subject><subject>Phosphinic Acids - chemical synthesis</subject><subject>Phosphinic Acids - chemistry</subject><subject>Phosphinic Acids - pharmacology</subject><subject>Proteinase</subject><subject>proteinases</subject><subject>quinoline</subject><subject>Quinolines</subject><subject>Swine</subject><subject>Viral Nonstructural Proteins - antagonists & inhibitors</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc2O0zAUhS0EYjoDL8ACvEGwScf_jRGbqgMD0ggWZSR2luPcEFdpEmw3qC_Ac-OoBXazsq71nXN_DkIvKFlSQtX1blntXbdkhNIlZUvCy0doQYUSBRdEPkYLohUpSi2-X6DLGHeEUEGEeIouGGNCaF4u0O8bH90wQTjiocG320Izqd7hNe7zZ4fHdohj63vvsHW-xjUEP0GNfd_6yqchzKrUAm5htMknH_EGTz4cIv6y5ddijccwJLAR8C-fWjzmok_YdbOl7bJp8pNPx2foSWO7CM_P7xW6__jh2-ZTcff19vNmfVc4IVgqnAOmV8QKqZRjlVZCMcss1RW3Tta0BMndqiRNo7kUTVM5wZ1SSjAiNbOcX6E3J9881s8DxGT2eX_oOtvDcIhG01KudMlpJt8-SOYEBCUrRXRG2Ql1YYgxQGPG4Pc2HDM0c8rszJyUmZMylJmcVBa9PPsfqj3U_yR_o8nA6zNgYz5VE2zvfPzPSTE3l5l7deIaOxj7I2Tmfps7yRw3l1rOq7w_EZAvO3kIJjoPvYPaB3DJ1IN_aNI_R6W5ng</recordid><startdate>20120201</startdate><enddate>20120201</enddate><creator>Sheng, X. 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Christopher ; Casarez, Anthony ; Cai, Ruby ; Clarke, Michael O. ; Chen, Xiaowu ; Cho, Aesop ; Delaney, William E. ; Doerffler, Edward ; Ji, Mingzhe ; Mertzman, Michael ; Pakdaman, Rowchanak ; Pyun, Hyung-Jung ; Rowe, Tanisha ; Wu, Qiaoyin ; Xu, Jie ; Kim, Choung U.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c442t-cce2970a4566c2b96462a2a19b3ac5d18e53c780ff9354ffbc43c666420592a33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Antibiotics. Antiinfectious agents. 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Christopher</au><au>Casarez, Anthony</au><au>Cai, Ruby</au><au>Clarke, Michael O.</au><au>Chen, Xiaowu</au><au>Cho, Aesop</au><au>Delaney, William E.</au><au>Doerffler, Edward</au><au>Ji, Mingzhe</au><au>Mertzman, Michael</au><au>Pakdaman, Rowchanak</au><au>Pyun, Hyung-Jung</au><au>Rowe, Tanisha</au><au>Wu, Qiaoyin</au><au>Xu, Jie</au><au>Kim, Choung U.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Discovery of GS-9256: A novel phosphinic acid derived inhibitor of the hepatitis C virus NS3/4A protease with potent clinical activity</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2012-02-01</date><risdate>2012</risdate><volume>22</volume><issue>3</issue><spage>1394</spage><epage>1396</epage><pages>1394-1396</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>A potent and novel class of phosphinic acid derived product-like inhibitors of the HCV NS3/4A protease was discovered previously. Modification of the phosphinic acid and quinoline heterocycle led to GS-9256 with potent cell-based activity and favorable pharmacokinetic parameters. Based on these attributes, GS-9256 was advanced to human clinical trial as a treatment for chronic infection with genotype 1 HCV.</abstract><cop>Amsterdam</cop><pub>Elsevier Ltd</pub><pmid>22244938</pmid><doi>10.1016/j.bmcl.2011.12.038</doi><tpages>3</tpages></addata></record> |
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| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2012-02, Vol.22 (3), p.1394-1396 |
| issn | 0960-894X 1464-3405 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animals Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral agents Biological and medical sciences Carboxylate isostere Carrier Proteins - antagonists & inhibitors Chronic infection Clinical trials Dogs Drug Discovery Enzyme Inhibitors - chemical synthesis Enzyme Inhibitors - chemistry Enzyme Inhibitors - pharmacology genotype Genotypes GS-9256 HCV Hepacivirus - drug effects Hepacivirus - enzymology Hepatitis C virus Humans Inhibitory Concentration 50 Medical sciences Molecular Structure NS3/4A protease inhibitor Peptides, Cyclic - chemical synthesis Peptides, Cyclic - chemistry Peptides, Cyclic - pharmacology Pharmacokinetics Pharmacology. Drug treatments Phosphinic acid Phosphinic Acids - chemical synthesis Phosphinic Acids - chemistry Phosphinic Acids - pharmacology Proteinase proteinases quinoline Quinolines Swine Viral Nonstructural Proteins - antagonists & inhibitors |
| title | Discovery of GS-9256: A novel phosphinic acid derived inhibitor of the hepatitis C virus NS3/4A protease with potent clinical activity |
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