First Total Synthesis of Phenylpyridine Analogues of the Antimitotic Rhazinilam
The first synthesis of phenylpyridine analogues of rhazinilam and evaluation of these new structures as inhibitors of microtubule disassembly by interaction with tubulin are described. The synthesis is based on such key steps as picolinic metalation, hetero-ring cross-coupling and reduction of an ac...
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| Veröffentlicht in: | Journal of organic chemistry 2001-04, Vol.66 (8), p.2654-2661 |
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| container_end_page | 2661 |
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| container_issue | 8 |
| container_start_page | 2654 |
| container_title | Journal of organic chemistry |
| container_volume | 66 |
| creator | Pasquinet, Eric Rocca, Patrick Richalot, Sébastien Guéritte, Françoise Guénard, Daniel Godard, Alain Marsais, Francis Quéguiner, Guy |
| description | The first synthesis of phenylpyridine analogues of rhazinilam and evaluation of these new structures as inhibitors of microtubule disassembly by interaction with tubulin are described. The synthesis is based on such key steps as picolinic metalation, hetero-ring cross-coupling and reduction of an acetyl group to an ethyl group. Elaboration of a quaternary picolinic carbon is one of the challenges of the synthesis. Biological evaluation of compounds bearing a quaternary picolinic carbon showed interactions with tubulin similar to (−)-rhazinilam but at a lower level. |
| doi_str_mv | 10.1021/jo0014156 |
| format | Article |
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The synthesis is based on such key steps as picolinic metalation, hetero-ring cross-coupling and reduction of an acetyl group to an ethyl group. Elaboration of a quaternary picolinic carbon is one of the challenges of the synthesis. Biological evaluation of compounds bearing a quaternary picolinic carbon showed interactions with tubulin similar to (−)-rhazinilam but at a lower level.</description><identifier>ISSN: 0022-3263</identifier><identifier>EISSN: 1520-6904</identifier><identifier>DOI: 10.1021/jo0014156</identifier><identifier>PMID: 11304183</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Alkaloids - chemical synthesis ; Alkaloids - pharmacology ; Animals ; Antineoplastic Agents - chemical synthesis ; Antineoplastic Agents - pharmacology ; Humans ; Indolizines ; Inhibitory Concentration 50 ; Lactams ; Microtubules - drug effects ; Pyridines - chemical synthesis ; Pyridines - pharmacology ; Stereoisomerism ; Tubulin Modulators</subject><ispartof>Journal of organic chemistry, 2001-04, Vol.66 (8), p.2654-2661</ispartof><rights>Copyright © 2001 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a349t-e21b34ca48956a9671f1f17fc6a4c99dc8d69718189bfceb9db034f78386e7c33</citedby><cites>FETCH-LOGICAL-a349t-e21b34ca48956a9671f1f17fc6a4c99dc8d69718189bfceb9db034f78386e7c33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jo0014156$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jo0014156$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11304183$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pasquinet, Eric</creatorcontrib><creatorcontrib>Rocca, Patrick</creatorcontrib><creatorcontrib>Richalot, Sébastien</creatorcontrib><creatorcontrib>Guéritte, Françoise</creatorcontrib><creatorcontrib>Guénard, Daniel</creatorcontrib><creatorcontrib>Godard, Alain</creatorcontrib><creatorcontrib>Marsais, Francis</creatorcontrib><creatorcontrib>Quéguiner, Guy</creatorcontrib><title>First Total Synthesis of Phenylpyridine Analogues of the Antimitotic Rhazinilam</title><title>Journal of organic chemistry</title><addtitle>J. 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| identifier | ISSN: 0022-3263 |
| ispartof | Journal of organic chemistry, 2001-04, Vol.66 (8), p.2654-2661 |
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| language | eng |
| recordid | cdi_crossref_primary_10_1021_jo0014156 |
| source | MEDLINE; American Chemical Society Web Editions |
| subjects | Alkaloids - chemical synthesis Alkaloids - pharmacology Animals Antineoplastic Agents - chemical synthesis Antineoplastic Agents - pharmacology Humans Indolizines Inhibitory Concentration 50 Lactams Microtubules - drug effects Pyridines - chemical synthesis Pyridines - pharmacology Stereoisomerism Tubulin Modulators |
| title | First Total Synthesis of Phenylpyridine Analogues of the Antimitotic Rhazinilam |
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