The rational design of inhibitors of nitric oxide formation by inducible nitric oxide synthase
A novel class of compounds that block nitric oxide formation from cells overexpressing iNOS is described. A series of compounds was rationally designed as inhibitors of dimer formation of the inducible isoform of nitric oxide synthase, and subsequent nitric oxide production. The conformation of two...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2007-05, Vol.17 (9), p.2505-2508 |
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| container_title | Bioorganic & medicinal chemistry letters |
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| creator | Whitlow, Marc Adler, Marc Davey, David Huang, Qinglan Koovakkat, Sunil Parkinson, John F. Pham, Eric Polokoff, Mark Xu, Wei Yuan, Shendong Phillips, Gary |
| description | A novel class of compounds that block nitric oxide formation from cells overexpressing iNOS is described.
A series of compounds was rationally designed as inhibitors of dimer formation of the inducible isoform of nitric oxide synthase, and subsequent nitric oxide production. The conformation of two fragments obtained from a crystal structure was utilized to design a tether connecting those same two fragments. The resulting compounds were potent dimerization inhibitors that bound to the enzyme in a similar conformation as the fragments. |
| doi_str_mv | 10.1016/j.bmcl.2007.02.018 |
| format | Article |
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A series of compounds was rationally designed as inhibitors of dimer formation of the inducible isoform of nitric oxide synthase, and subsequent nitric oxide production. The conformation of two fragments obtained from a crystal structure was utilized to design a tether connecting those same two fragments. The resulting compounds were potent dimerization inhibitors that bound to the enzyme in a similar conformation as the fragments.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2007.02.018</identifier><identifier>PMID: 17336523</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Analytical, structural and metabolic biochemistry ; Binding Sites ; Biological and medical sciences ; Cell Line, Tumor ; Chemistry, Pharmaceutical - methods ; Crystallization ; Crystallography, X-Ray ; Dimerization ; Dimerization inhibitors ; Drug Design ; Enzyme Inhibitors - chemical synthesis ; Enzyme Inhibitors - pharmacology ; Enzymes and enzyme inhibitors ; Fundamental and applied biological sciences. Psychology ; Humans ; iNOS ; Medical sciences ; Miscellaneous ; Models, Chemical ; Molecular Conformation ; Nitric Oxide Synthase Type II - antagonists & inhibitors ; Oxidoreductases ; Pharmacology. Drug treatments</subject><ispartof>Bioorganic & medicinal chemistry letters, 2007-05, Vol.17 (9), p.2505-2508</ispartof><rights>2007 Elsevier Ltd</rights><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c415t-91bfbd6ccdf4ee310f17b44faeaf5082aa1caf1c08c0649614b2ee65fc93fd533</citedby><cites>FETCH-LOGICAL-c415t-91bfbd6ccdf4ee310f17b44faeaf5082aa1caf1c08c0649614b2ee65fc93fd533</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0960894X07002053$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18676928$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17336523$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Whitlow, Marc</creatorcontrib><creatorcontrib>Adler, Marc</creatorcontrib><creatorcontrib>Davey, David</creatorcontrib><creatorcontrib>Huang, Qinglan</creatorcontrib><creatorcontrib>Koovakkat, Sunil</creatorcontrib><creatorcontrib>Parkinson, John F.</creatorcontrib><creatorcontrib>Pham, Eric</creatorcontrib><creatorcontrib>Polokoff, Mark</creatorcontrib><creatorcontrib>Xu, Wei</creatorcontrib><creatorcontrib>Yuan, Shendong</creatorcontrib><creatorcontrib>Phillips, Gary</creatorcontrib><title>The rational design of inhibitors of nitric oxide formation by inducible nitric oxide synthase</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>A novel class of compounds that block nitric oxide formation from cells overexpressing iNOS is described.
A series of compounds was rationally designed as inhibitors of dimer formation of the inducible isoform of nitric oxide synthase, and subsequent nitric oxide production. The conformation of two fragments obtained from a crystal structure was utilized to design a tether connecting those same two fragments. The resulting compounds were potent dimerization inhibitors that bound to the enzyme in a similar conformation as the fragments.</description><subject>Analytical, structural and metabolic biochemistry</subject><subject>Binding Sites</subject><subject>Biological and medical sciences</subject><subject>Cell Line, Tumor</subject><subject>Chemistry, Pharmaceutical - methods</subject><subject>Crystallization</subject><subject>Crystallography, X-Ray</subject><subject>Dimerization</subject><subject>Dimerization inhibitors</subject><subject>Drug Design</subject><subject>Enzyme Inhibitors - chemical synthesis</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Enzymes and enzyme inhibitors</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>iNOS</subject><subject>Medical sciences</subject><subject>Miscellaneous</subject><subject>Models, Chemical</subject><subject>Molecular Conformation</subject><subject>Nitric Oxide Synthase Type II - antagonists & inhibitors</subject><subject>Oxidoreductases</subject><subject>Pharmacology. 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A series of compounds was rationally designed as inhibitors of dimer formation of the inducible isoform of nitric oxide synthase, and subsequent nitric oxide production. The conformation of two fragments obtained from a crystal structure was utilized to design a tether connecting those same two fragments. The resulting compounds were potent dimerization inhibitors that bound to the enzyme in a similar conformation as the fragments.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>17336523</pmid><doi>10.1016/j.bmcl.2007.02.018</doi><tpages>4</tpages></addata></record> |
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| ispartof | Bioorganic & medicinal chemistry letters, 2007-05, Vol.17 (9), p.2505-2508 |
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| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Analytical, structural and metabolic biochemistry Binding Sites Biological and medical sciences Cell Line, Tumor Chemistry, Pharmaceutical - methods Crystallization Crystallography, X-Ray Dimerization Dimerization inhibitors Drug Design Enzyme Inhibitors - chemical synthesis Enzyme Inhibitors - pharmacology Enzymes and enzyme inhibitors Fundamental and applied biological sciences. Psychology Humans iNOS Medical sciences Miscellaneous Models, Chemical Molecular Conformation Nitric Oxide Synthase Type II - antagonists & inhibitors Oxidoreductases Pharmacology. Drug treatments |
| title | The rational design of inhibitors of nitric oxide formation by inducible nitric oxide synthase |
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