Synthesis and analgesic evaluation of 4-(2-heptyloxy)-7-[(Z)-(3-hydroxycyclohexyl)]indole: a caveat on indole-phenol bioisosterism
The synthesis of 4-(2-heptyloxy)-7-[(Z)-(3-hydroxycyclohexyl)]indole (7) is described. Compound 7 was tested for analgesic properties in the phenylbenzoquinone writhing test and was found to be essentially devoid of activity. In contrast, cis-3-[4-(2-heptyloxy)-2-hydroxyphenyl]cyclohexanol (8), the...
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| Veröffentlicht in: | Journal of medicinal chemistry 1986-08, Vol.29 (8), p.1457-1460 |
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| container_title | Journal of medicinal chemistry |
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| creator | Soll, Richard M Humber, Leslie G Deininger, David Asselin, Andre A Chau, Thuy T Weichman, Barry M |
| description | The synthesis of 4-(2-heptyloxy)-7-[(Z)-(3-hydroxycyclohexyl)]indole (7) is described. Compound 7 was tested for analgesic properties in the phenylbenzoquinone writhing test and was found to be essentially devoid of activity. In contrast, cis-3-[4-(2-heptyloxy)-2-hydroxyphenyl]cyclohexanol (8), the analogue in which the pyrrolo ring is replaced by a hydroxyl group, had an ED50 of 8.3 mg/kg, sc, in the same model. The absence of bioisosterism between the pyrrolo ring and the phenolic hydroxyl group, in this instance, is discussed in terms of the circumstances that control the manifestation of bioisofunctionality between a pyrrolo ring and a phenolic hydroxyl group, which functions as a hydrogen-bond donor. |
| doi_str_mv | 10.1021/jm00158a023 |
| format | Article |
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Compound 7 was tested for analgesic properties in the phenylbenzoquinone writhing test and was found to be essentially devoid of activity. In contrast, cis-3-[4-(2-heptyloxy)-2-hydroxyphenyl]cyclohexanol (8), the analogue in which the pyrrolo ring is replaced by a hydroxyl group, had an ED50 of 8.3 mg/kg, sc, in the same model. The absence of bioisosterism between the pyrrolo ring and the phenolic hydroxyl group, in this instance, is discussed in terms of the circumstances that control the manifestation of bioisofunctionality between a pyrrolo ring and a phenolic hydroxyl group, which functions as a hydrogen-bond donor.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm00158a023</identifier><identifier>PMID: 3735313</identifier><identifier>CODEN: JMCMAR</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Analgesics - chemical synthesis ; Animals ; Benzoquinones ; Chemistry ; Chromatography, Thin Layer ; Exact sciences and technology ; Heterocyclic compounds ; Heterocyclic compounds with only one n hetero atom and condensed derivatives ; Indoles - chemical synthesis ; Indoles - pharmacology ; Magnetic Resonance Spectroscopy ; Male ; Mice ; Organic chemistry ; Preparations and properties ; Quinones ; Structure-Activity Relationship</subject><ispartof>Journal of medicinal chemistry, 1986-08, Vol.29 (8), p.1457-1460</ispartof><rights>1987 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a383t-47a2d2bca328071366e34676883ead669c8caa1ae63d8521f0e08256669cc6b53</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jm00158a023$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm00158a023$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=7893299$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/3735313$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Soll, Richard M</creatorcontrib><creatorcontrib>Humber, Leslie G</creatorcontrib><creatorcontrib>Deininger, David</creatorcontrib><creatorcontrib>Asselin, Andre A</creatorcontrib><creatorcontrib>Chau, Thuy T</creatorcontrib><creatorcontrib>Weichman, Barry M</creatorcontrib><title>Synthesis and analgesic evaluation of 4-(2-heptyloxy)-7-[(Z)-(3-hydroxycyclohexyl)]indole: a caveat on indole-phenol bioisosterism</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>The synthesis of 4-(2-heptyloxy)-7-[(Z)-(3-hydroxycyclohexyl)]indole (7) is described. Compound 7 was tested for analgesic properties in the phenylbenzoquinone writhing test and was found to be essentially devoid of activity. In contrast, cis-3-[4-(2-heptyloxy)-2-hydroxyphenyl]cyclohexanol (8), the analogue in which the pyrrolo ring is replaced by a hydroxyl group, had an ED50 of 8.3 mg/kg, sc, in the same model. The absence of bioisosterism between the pyrrolo ring and the phenolic hydroxyl group, in this instance, is discussed in terms of the circumstances that control the manifestation of bioisofunctionality between a pyrrolo ring and a phenolic hydroxyl group, which functions as a hydrogen-bond donor.</description><subject>Analgesics - chemical synthesis</subject><subject>Animals</subject><subject>Benzoquinones</subject><subject>Chemistry</subject><subject>Chromatography, Thin Layer</subject><subject>Exact sciences and technology</subject><subject>Heterocyclic compounds</subject><subject>Heterocyclic compounds with only one n hetero atom and condensed derivatives</subject><subject>Indoles - chemical synthesis</subject><subject>Indoles - pharmacology</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Male</subject><subject>Mice</subject><subject>Organic chemistry</subject><subject>Preparations and properties</subject><subject>Quinones</subject><subject>Structure-Activity Relationship</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1986</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkc-L1DAcxYMo67h68iz0IOsMEs2PNk29yeKqMODCjiCKhO-kqc2YNmPSLtOrf7lZOwwePISQ9z6875cXhJ5S8ooSRl_vOkJoIYEwfg8taMEIziXJ76MFIYxhJhh_iB7FuCOEcMr4GTrjJS845Qv0-2bqh9ZEGzPo63TA_UgvnZlbcCMM1veZb7IcLxluzX6YnD9MK1zib8uvK7zkuJ3qkCQ9aedbc5jc6rvta-_MmwwyDbcGhixlzBret6b3Lttab6OPgwk2do_RgwZcNE-O9zn6fPVuc_kBrz-9_3j5do2BSz7gvARWs60GziQpKRfC8FyUQkpuoBai0lIDUDCC17JgtCGGSFaIO0eLbcHP0cWcuw_-12jioDobtXEOeuPHqEpRFTKvqgS-nEEdfIzBNGofbAdhUpSou8bVP40n-tkxdtx2pj6xx4qT__zoQ9TgmgC9tvGElbLi7O9QPGM21XI42RB-KlHyslCb6xuVi_UVKzbX6kviX8w86Kh2fgzp5-J_F_wDN62jrQ</recordid><startdate>19860801</startdate><enddate>19860801</enddate><creator>Soll, Richard M</creator><creator>Humber, Leslie G</creator><creator>Deininger, David</creator><creator>Asselin, Andre A</creator><creator>Chau, Thuy T</creator><creator>Weichman, Barry M</creator><general>American Chemical Society</general><scope>BSCLL</scope><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>19860801</creationdate><title>Synthesis and analgesic evaluation of 4-(2-heptyloxy)-7-[(Z)-(3-hydroxycyclohexyl)]indole: a caveat on indole-phenol bioisosterism</title><author>Soll, Richard M ; Humber, Leslie G ; Deininger, David ; Asselin, Andre A ; Chau, Thuy T ; Weichman, Barry M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a383t-47a2d2bca328071366e34676883ead669c8caa1ae63d8521f0e08256669cc6b53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1986</creationdate><topic>Analgesics - chemical synthesis</topic><topic>Animals</topic><topic>Benzoquinones</topic><topic>Chemistry</topic><topic>Chromatography, Thin Layer</topic><topic>Exact sciences and technology</topic><topic>Heterocyclic compounds</topic><topic>Heterocyclic compounds with only one n hetero atom and condensed derivatives</topic><topic>Indoles - chemical synthesis</topic><topic>Indoles - pharmacology</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Male</topic><topic>Mice</topic><topic>Organic chemistry</topic><topic>Preparations and properties</topic><topic>Quinones</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Soll, Richard M</creatorcontrib><creatorcontrib>Humber, Leslie G</creatorcontrib><creatorcontrib>Deininger, David</creatorcontrib><creatorcontrib>Asselin, Andre A</creatorcontrib><creatorcontrib>Chau, Thuy T</creatorcontrib><creatorcontrib>Weichman, Barry M</creatorcontrib><collection>Istex</collection><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>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Soll, Richard M</au><au>Humber, Leslie G</au><au>Deininger, David</au><au>Asselin, Andre A</au><au>Chau, Thuy T</au><au>Weichman, Barry M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis and analgesic evaluation of 4-(2-heptyloxy)-7-[(Z)-(3-hydroxycyclohexyl)]indole: a caveat on indole-phenol bioisosterism</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>1986-08-01</date><risdate>1986</risdate><volume>29</volume><issue>8</issue><spage>1457</spage><epage>1460</epage><pages>1457-1460</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><abstract>The synthesis of 4-(2-heptyloxy)-7-[(Z)-(3-hydroxycyclohexyl)]indole (7) is described. Compound 7 was tested for analgesic properties in the phenylbenzoquinone writhing test and was found to be essentially devoid of activity. In contrast, cis-3-[4-(2-heptyloxy)-2-hydroxyphenyl]cyclohexanol (8), the analogue in which the pyrrolo ring is replaced by a hydroxyl group, had an ED50 of 8.3 mg/kg, sc, in the same model. The absence of bioisosterism between the pyrrolo ring and the phenolic hydroxyl group, in this instance, is discussed in terms of the circumstances that control the manifestation of bioisofunctionality between a pyrrolo ring and a phenolic hydroxyl group, which functions as a hydrogen-bond donor.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>3735313</pmid><doi>10.1021/jm00158a023</doi><tpages>4</tpages></addata></record> |
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| ispartof | Journal of medicinal chemistry, 1986-08, Vol.29 (8), p.1457-1460 |
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| source | MEDLINE; American Chemical Society Journals |
| subjects | Analgesics - chemical synthesis Animals Benzoquinones Chemistry Chromatography, Thin Layer Exact sciences and technology Heterocyclic compounds Heterocyclic compounds with only one n hetero atom and condensed derivatives Indoles - chemical synthesis Indoles - pharmacology Magnetic Resonance Spectroscopy Male Mice Organic chemistry Preparations and properties Quinones Structure-Activity Relationship |
| title | Synthesis and analgesic evaluation of 4-(2-heptyloxy)-7-[(Z)-(3-hydroxycyclohexyl)]indole: a caveat on indole-phenol bioisosterism |
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