Prodrugs for targeting hypoxic tissues: Regiospecific elimination of aspirin from reduced indolequinones
A series of regioisomeric derivatives of a 1-methylindole-4,7-dione were synthesised, substituted with a 2-acetoxybenzoate leaving group linked through the (indol-2-yl)methyl or (indol-3-yl)methyl (or propenyl) positions. Reductive elimination of the leaving group occurred from the (indol-3-yl)methy...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 1999-01, Vol.9 (1), p.113-118 |
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| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 9 |
| creator | Jaffar, M Everett, S.A Naylor, M.A Moore, S.G Ulhaq, S Patel, K.B Stratford, M.R.L Nolan, J Wardman, P Stratford, I.J |
| description | A series of regioisomeric derivatives of a 1-methylindole-4,7-dione were synthesised, substituted with a 2-acetoxybenzoate leaving group linked through the (indol-2-yl)methyl or (indol-3-yl)methyl (or propenyl) positions. Reductive elimination of the leaving group occurred from the (indol-3-yl)methyl derivatives but not the 2-substituted regioisomers, indicating that only the C-3 position may be utilised in bioreductively-activated drug delivery, which was demonstrated with an aspirin prodrug.
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| doi_str_mv | 10.1016/S0960-894X(98)00695-7 |
| format | Article |
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Graphic</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/S0960-894X(98)00695-7</identifier><identifier>PMID: 9990467</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Animals ; Anti-Inflammatory Agents, Non-Steroidal ; Antineoplastic agents ; Arthritis - metabolism ; Aspirin - chemistry ; Aspirin - metabolism ; Biological and medical sciences ; Free Radicals - metabolism ; General aspects ; Humans ; Hypoxia - drug therapy ; Hypoxia - metabolism ; Indoles - chemistry ; Indoles - metabolism ; Medical sciences ; Neoplasms - metabolism ; Oxidation-Reduction ; Pharmacology. Drug treatments ; Prodrugs - chemistry ; Prodrugs - metabolism ; Quinones - chemistry ; Quinones - metabolism ; Structure-Activity Relationship</subject><ispartof>Bioorganic & medicinal chemistry letters, 1999-01, Vol.9 (1), p.113-118</ispartof><rights>1998</rights><rights>1999 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c389t-7611ae0fb685146009ec1a07b7919adcca7320f8fb2c83f605fd85c99fb67d6d3</citedby><cites>FETCH-LOGICAL-c389t-7611ae0fb685146009ec1a07b7919adcca7320f8fb2c83f605fd85c99fb67d6d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0960-894X(98)00695-7$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1665187$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9990467$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jaffar, M</creatorcontrib><creatorcontrib>Everett, S.A</creatorcontrib><creatorcontrib>Naylor, M.A</creatorcontrib><creatorcontrib>Moore, S.G</creatorcontrib><creatorcontrib>Ulhaq, S</creatorcontrib><creatorcontrib>Patel, K.B</creatorcontrib><creatorcontrib>Stratford, M.R.L</creatorcontrib><creatorcontrib>Nolan, J</creatorcontrib><creatorcontrib>Wardman, P</creatorcontrib><creatorcontrib>Stratford, I.J</creatorcontrib><title>Prodrugs for targeting hypoxic tissues: Regiospecific elimination of aspirin from reduced indolequinones</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>A series of regioisomeric derivatives of a 1-methylindole-4,7-dione were synthesised, substituted with a 2-acetoxybenzoate leaving group linked through the (indol-2-yl)methyl or (indol-3-yl)methyl (or propenyl) positions. Reductive elimination of the leaving group occurred from the (indol-3-yl)methyl derivatives but not the 2-substituted regioisomers, indicating that only the C-3 position may be utilised in bioreductively-activated drug delivery, which was demonstrated with an aspirin prodrug.
Graphic</description><subject>Animals</subject><subject>Anti-Inflammatory Agents, Non-Steroidal</subject><subject>Antineoplastic agents</subject><subject>Arthritis - metabolism</subject><subject>Aspirin - chemistry</subject><subject>Aspirin - metabolism</subject><subject>Biological and medical sciences</subject><subject>Free Radicals - metabolism</subject><subject>General aspects</subject><subject>Humans</subject><subject>Hypoxia - drug therapy</subject><subject>Hypoxia - metabolism</subject><subject>Indoles - chemistry</subject><subject>Indoles - metabolism</subject><subject>Medical sciences</subject><subject>Neoplasms - metabolism</subject><subject>Oxidation-Reduction</subject><subject>Pharmacology. Drug treatments</subject><subject>Prodrugs - chemistry</subject><subject>Prodrugs - metabolism</subject><subject>Quinones - chemistry</subject><subject>Quinones - metabolism</subject><subject>Structure-Activity Relationship</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkF1rFTEQhoMo9Vj9CYVciOjF1qS7mw9vRIq2hULFD_Au5CST05HdZJvsSvvvm9NzaC-9Gsg878zkIeSIs2POuPj4k2nBGqW7P--1-sCY0H0jn5EV70TXtB3rn5PVI_KSvCrlL2O8Y113QA601qwTckWuv-fk87IpNKRMZ5s3MGPc0Ou7Kd2iozOWskD5RH_ABlOZwGGozzDgiNHOmCJNgdoyYcZIQ04jzeAXB55i9GmAmwVjilBekxfBDgXe7Osh-f3t66_T8-by6uzi9Mtl41ql50YKzi2wsBaqrz9hTIPjlsm11Fxb75yV7QkLKqxPnGqDYH3wqnda14T0wreH5N1u7pTTTb18NiMWB8NgI6SlmKpJStXyCvY70OVUSoZgpoyjzXeGM7M1bB4Mm60-o5V5MGxkzR3tFyzrEfxjaq-09t_u-7Y4O4Rso8PyNFyInqst9nmHQZXxDyGb4hBiFYcZ3Gx8wv8ccg93ipsO</recordid><startdate>19990104</startdate><enddate>19990104</enddate><creator>Jaffar, M</creator><creator>Everett, S.A</creator><creator>Naylor, M.A</creator><creator>Moore, S.G</creator><creator>Ulhaq, S</creator><creator>Patel, K.B</creator><creator>Stratford, M.R.L</creator><creator>Nolan, J</creator><creator>Wardman, P</creator><creator>Stratford, I.J</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>19990104</creationdate><title>Prodrugs for targeting hypoxic tissues: Regiospecific elimination of aspirin from reduced indolequinones</title><author>Jaffar, M ; Everett, S.A ; Naylor, M.A ; Moore, S.G ; Ulhaq, S ; Patel, K.B ; Stratford, M.R.L ; Nolan, J ; Wardman, P ; Stratford, I.J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c389t-7611ae0fb685146009ec1a07b7919adcca7320f8fb2c83f605fd85c99fb67d6d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Animals</topic><topic>Anti-Inflammatory Agents, Non-Steroidal</topic><topic>Antineoplastic agents</topic><topic>Arthritis - metabolism</topic><topic>Aspirin - chemistry</topic><topic>Aspirin - metabolism</topic><topic>Biological and medical sciences</topic><topic>Free Radicals - metabolism</topic><topic>General aspects</topic><topic>Humans</topic><topic>Hypoxia - drug therapy</topic><topic>Hypoxia - metabolism</topic><topic>Indoles - chemistry</topic><topic>Indoles - metabolism</topic><topic>Medical sciences</topic><topic>Neoplasms - metabolism</topic><topic>Oxidation-Reduction</topic><topic>Pharmacology. 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Reductive elimination of the leaving group occurred from the (indol-3-yl)methyl derivatives but not the 2-substituted regioisomers, indicating that only the C-3 position may be utilised in bioreductively-activated drug delivery, which was demonstrated with an aspirin prodrug.
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| ispartof | Bioorganic & medicinal chemistry letters, 1999-01, Vol.9 (1), p.113-118 |
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| language | eng |
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| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | Animals Anti-Inflammatory Agents, Non-Steroidal Antineoplastic agents Arthritis - metabolism Aspirin - chemistry Aspirin - metabolism Biological and medical sciences Free Radicals - metabolism General aspects Humans Hypoxia - drug therapy Hypoxia - metabolism Indoles - chemistry Indoles - metabolism Medical sciences Neoplasms - metabolism Oxidation-Reduction Pharmacology. Drug treatments Prodrugs - chemistry Prodrugs - metabolism Quinones - chemistry Quinones - metabolism Structure-Activity Relationship |
| title | Prodrugs for targeting hypoxic tissues: Regiospecific elimination of aspirin from reduced indolequinones |
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