Thrombin inhibitors built on an azaphenylalanine scaffold
A series of azaphenylalanine derivatives were investigated as novel thrombin inhibitors based on the prodrug principle. By systematic structural modifications we have identified optimal groups for this series that led us to potent inhibitors of thrombin incorporating the benzamidine fragment at the...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2004-03, Vol.14 (6), p.1563-1567 |
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| container_end_page | 1567 |
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| container_issue | 6 |
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| container_title | Bioorganic & medicinal chemistry letters |
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| creator | Zega, Anamarija Mlinšek, Gregor Šolmajer, Tomaž Trampuš-Bakija, Alenka Stegnar, Mojca Urleb, Uroš |
| description | A series of azaphenylalanine derivatives were investigated as novel thrombin inhibitors based on the prodrug principle. By systematic structural modifications we have identified optimal groups for this series that led us to potent inhibitors of thrombin incorporating the benzamidine fragment at the P1 position, and their potentially orally active benzamidoxime prodrugs. The binding modes in the thrombin active site of two representative compounds were identified by X-ray crystallographic analysis.
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| doi_str_mv | 10.1016/j.bmcl.2003.12.083 |
| format | Article |
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Blood coagulation. Reticuloendothelial system</topic><topic>Medical sciences</topic><topic>Pharmacology. Drug treatments</topic><topic>Phenylalanine - chemistry</topic><topic>Phenylalanine - metabolism</topic><topic>Prodrug</topic><topic>Protein Binding</topic><topic>Serine Proteinase Inhibitors - chemical synthesis</topic><topic>Serine Proteinase Inhibitors - metabolism</topic><topic>Thrombin - antagonists & inhibitors</topic><topic>Thrombin - metabolism</topic><topic>Thrombin inhibitors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zega, Anamarija</creatorcontrib><creatorcontrib>Mlinšek, Gregor</creatorcontrib><creatorcontrib>Šolmajer, Tomaž</creatorcontrib><creatorcontrib>Trampuš-Bakija, Alenka</creatorcontrib><creatorcontrib>Stegnar, Mojca</creatorcontrib><creatorcontrib>Urleb, Uroš</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>Zega, Anamarija</au><au>Mlinšek, Gregor</au><au>Šolmajer, Tomaž</au><au>Trampuš-Bakija, Alenka</au><au>Stegnar, Mojca</au><au>Urleb, Uroš</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Thrombin inhibitors built on an azaphenylalanine scaffold</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2004-03-22</date><risdate>2004</risdate><volume>14</volume><issue>6</issue><spage>1563</spage><epage>1567</epage><pages>1563-1567</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>A series of azaphenylalanine derivatives were investigated as novel thrombin inhibitors based on the prodrug principle. By systematic structural modifications we have identified optimal groups for this series that led us to potent inhibitors of thrombin incorporating the benzamidine fragment at the P1 position, and their potentially orally active benzamidoxime prodrugs. The binding modes in the thrombin active site of two representative compounds were identified by X-ray crystallographic analysis.
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| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2004-03, Vol.14 (6), p.1563-1567 |
| issn | 0960-894X 1464-3405 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Aza Compounds - chemistry Aza Compounds - metabolism Azapeptidomimetics Biological and medical sciences Blood. Blood coagulation. Reticuloendothelial system Medical sciences Pharmacology. Drug treatments Phenylalanine - chemistry Phenylalanine - metabolism Prodrug Protein Binding Serine Proteinase Inhibitors - chemical synthesis Serine Proteinase Inhibitors - metabolism Thrombin - antagonists & inhibitors Thrombin - metabolism Thrombin inhibitors |
| title | Thrombin inhibitors built on an azaphenylalanine scaffold |
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