Nonbenzamidine isoxazoline derivatives as factor Xa inhibitors
Factor Xa (fXa) is an important serine protease in the blood coagulation cascade. Inhibition of fXa has emerged as an attractive target for potential therapeutic applications in the treatments of both arterial and venous thrombosis. Herein, we describe a series of non-benzamidine isoxazoline derivat...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2003-03, Vol.13 (6), p.1023-1028 |
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| container_title | Bioorganic & medicinal chemistry letters |
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| creator | Quan, Mimi L. Ellis, Christopher D. He, Ming Y. Liauw, Ann Y. Lam, Patrick Y.S. Rossi, Karen A. Knabb, Robert M. Luettgen, Joseph M. Wright, Matthew R. Wong, Pancras C. Wexler, Ruth R. |
| description | Factor Xa (fXa) is an important serine protease in the blood coagulation cascade. Inhibition of fXa has emerged as an attractive target for potential therapeutic applications in the treatments of both arterial and venous thrombosis. Herein, we describe a series of non-benzamidine isoxazoline derivatives as fXa inhibitors. The chloroaniline group was found to be the most potent benzamidine mimic in this series. Chloroaniline
1 (ST368) has a
K
i value of 1.5 nM against fXa and is highly selective for fXa relative to thrombin and trypsin.
A series of nonbenzamidine isoxazoline fXa inhibitors is described. The chloroaniline group was found to be the most potent benzamidine mimic in this series. Chloroaniline
1 (ST368) has a
K
i value of 1.2 nM against fXa and is highly selective for fXa relative to thrombin and trypsin. |
| doi_str_mv | 10.1016/S0960-894X(03)00080-5 |
| format | Article |
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1 (ST368) has a
K
i value of 1.5 nM against fXa and is highly selective for fXa relative to thrombin and trypsin.
A series of nonbenzamidine isoxazoline fXa inhibitors is described. The chloroaniline group was found to be the most potent benzamidine mimic in this series. Chloroaniline
1 (ST368) has a
K
i value of 1.2 nM against fXa and is highly selective for fXa relative to thrombin and trypsin.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/S0960-894X(03)00080-5</identifier><identifier>PMID: 12643903</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Animals ; Biological and medical sciences ; Biological Availability ; Blood. Blood coagulation. Reticuloendothelial system ; Chromatography, High Pressure Liquid ; Dogs ; Factor Xa Inhibitors ; Fibrinolytic Agents - chemical synthesis ; Fibrinolytic Agents - pharmacokinetics ; Fibrinolytic Agents - pharmacology ; Half-Life ; Humans ; In Vitro Techniques ; Indicators and Reagents ; Isoxazoles - chemical synthesis ; Isoxazoles - pharmacokinetics ; Isoxazoles - pharmacology ; Kinetics ; Medical sciences ; Models, Molecular ; Pharmacology. Drug treatments ; Rabbits</subject><ispartof>Bioorganic & medicinal chemistry letters, 2003-03, Vol.13 (6), p.1023-1028</ispartof><rights>2003 Elsevier Science Ltd</rights><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c391t-7aaedc747f2013db037a151d752a209ee4d2774bebc4de5ee569402ec12548093</citedby><cites>FETCH-LOGICAL-c391t-7aaedc747f2013db037a151d752a209ee4d2774bebc4de5ee569402ec12548093</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0960894X03000805$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17190003$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12643903$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Quan, Mimi L.</creatorcontrib><creatorcontrib>Ellis, Christopher D.</creatorcontrib><creatorcontrib>He, Ming Y.</creatorcontrib><creatorcontrib>Liauw, Ann Y.</creatorcontrib><creatorcontrib>Lam, Patrick Y.S.</creatorcontrib><creatorcontrib>Rossi, Karen A.</creatorcontrib><creatorcontrib>Knabb, Robert M.</creatorcontrib><creatorcontrib>Luettgen, Joseph M.</creatorcontrib><creatorcontrib>Wright, Matthew R.</creatorcontrib><creatorcontrib>Wong, Pancras C.</creatorcontrib><creatorcontrib>Wexler, Ruth R.</creatorcontrib><title>Nonbenzamidine isoxazoline derivatives as factor Xa inhibitors</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>Factor Xa (fXa) is an important serine protease in the blood coagulation cascade. Inhibition of fXa has emerged as an attractive target for potential therapeutic applications in the treatments of both arterial and venous thrombosis. Herein, we describe a series of non-benzamidine isoxazoline derivatives as fXa inhibitors. The chloroaniline group was found to be the most potent benzamidine mimic in this series. Chloroaniline
1 (ST368) has a
K
i value of 1.5 nM against fXa and is highly selective for fXa relative to thrombin and trypsin.
A series of nonbenzamidine isoxazoline fXa inhibitors is described. The chloroaniline group was found to be the most potent benzamidine mimic in this series. Chloroaniline
1 (ST368) has a
K
i value of 1.2 nM against fXa and is highly selective for fXa relative to thrombin and trypsin.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Biological Availability</subject><subject>Blood. Blood coagulation. Reticuloendothelial system</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Dogs</subject><subject>Factor Xa Inhibitors</subject><subject>Fibrinolytic Agents - chemical synthesis</subject><subject>Fibrinolytic Agents - pharmacokinetics</subject><subject>Fibrinolytic Agents - pharmacology</subject><subject>Half-Life</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Indicators and Reagents</subject><subject>Isoxazoles - chemical synthesis</subject><subject>Isoxazoles - pharmacokinetics</subject><subject>Isoxazoles - pharmacology</subject><subject>Kinetics</subject><subject>Medical sciences</subject><subject>Models, Molecular</subject><subject>Pharmacology. 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Blood coagulation. Reticuloendothelial system</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Dogs</topic><topic>Factor Xa Inhibitors</topic><topic>Fibrinolytic Agents - chemical synthesis</topic><topic>Fibrinolytic Agents - pharmacokinetics</topic><topic>Fibrinolytic Agents - pharmacology</topic><topic>Half-Life</topic><topic>Humans</topic><topic>In Vitro Techniques</topic><topic>Indicators and Reagents</topic><topic>Isoxazoles - chemical synthesis</topic><topic>Isoxazoles - pharmacokinetics</topic><topic>Isoxazoles - pharmacology</topic><topic>Kinetics</topic><topic>Medical sciences</topic><topic>Models, Molecular</topic><topic>Pharmacology. Drug treatments</topic><topic>Rabbits</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Quan, Mimi L.</creatorcontrib><creatorcontrib>Ellis, Christopher D.</creatorcontrib><creatorcontrib>He, Ming Y.</creatorcontrib><creatorcontrib>Liauw, Ann Y.</creatorcontrib><creatorcontrib>Lam, Patrick Y.S.</creatorcontrib><creatorcontrib>Rossi, Karen A.</creatorcontrib><creatorcontrib>Knabb, Robert M.</creatorcontrib><creatorcontrib>Luettgen, Joseph M.</creatorcontrib><creatorcontrib>Wright, Matthew R.</creatorcontrib><creatorcontrib>Wong, Pancras C.</creatorcontrib><creatorcontrib>Wexler, Ruth R.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Quan, Mimi L.</au><au>Ellis, Christopher D.</au><au>He, Ming Y.</au><au>Liauw, Ann Y.</au><au>Lam, Patrick Y.S.</au><au>Rossi, Karen A.</au><au>Knabb, Robert M.</au><au>Luettgen, Joseph M.</au><au>Wright, Matthew R.</au><au>Wong, Pancras C.</au><au>Wexler, Ruth R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nonbenzamidine isoxazoline derivatives as factor Xa inhibitors</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2003-03-24</date><risdate>2003</risdate><volume>13</volume><issue>6</issue><spage>1023</spage><epage>1028</epage><pages>1023-1028</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>Factor Xa (fXa) is an important serine protease in the blood coagulation cascade. Inhibition of fXa has emerged as an attractive target for potential therapeutic applications in the treatments of both arterial and venous thrombosis. Herein, we describe a series of non-benzamidine isoxazoline derivatives as fXa inhibitors. The chloroaniline group was found to be the most potent benzamidine mimic in this series. Chloroaniline
1 (ST368) has a
K
i value of 1.5 nM against fXa and is highly selective for fXa relative to thrombin and trypsin.
A series of nonbenzamidine isoxazoline fXa inhibitors is described. The chloroaniline group was found to be the most potent benzamidine mimic in this series. Chloroaniline
1 (ST368) has a
K
i value of 1.2 nM against fXa and is highly selective for fXa relative to thrombin and trypsin.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>12643903</pmid><doi>10.1016/S0960-894X(03)00080-5</doi><tpages>6</tpages></addata></record> |
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| ispartof | Bioorganic & medicinal chemistry letters, 2003-03, Vol.13 (6), p.1023-1028 |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animals Biological and medical sciences Biological Availability Blood. Blood coagulation. Reticuloendothelial system Chromatography, High Pressure Liquid Dogs Factor Xa Inhibitors Fibrinolytic Agents - chemical synthesis Fibrinolytic Agents - pharmacokinetics Fibrinolytic Agents - pharmacology Half-Life Humans In Vitro Techniques Indicators and Reagents Isoxazoles - chemical synthesis Isoxazoles - pharmacokinetics Isoxazoles - pharmacology Kinetics Medical sciences Models, Molecular Pharmacology. Drug treatments Rabbits |
| title | Nonbenzamidine isoxazoline derivatives as factor Xa inhibitors |
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