Hybrid bivalent ligands with opiate and enkephalin pharmacophores
Bivalent ligands consisting of oxymorphamine and [D-Glu2]enkephalin pharmacophores linked through a spacer attached to the 6-amino group of the former and D-Glu of the latter were synthesized in an effort to investigate the possible coexistence of mu and delta recognition sites in the same opioid re...
Gespeichert in:
| Veröffentlicht in: | Journal of medicinal chemistry 1987-11, Vol.30 (11), p.1991-1994 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1994 |
|---|---|
| container_issue | 11 |
| container_start_page | 1991 |
| container_title | Journal of medicinal chemistry |
| container_volume | 30 |
| creator | Portoghese, Philip S Larson, D. L Ronsisvalle, G Schiller, P. W Nguyen Thi Mai Dung Lemieux, C Takemori, A. E |
| description | Bivalent ligands consisting of oxymorphamine and [D-Glu2]enkephalin pharmacophores linked through a spacer attached to the 6-amino group of the former and D-Glu of the latter were synthesized in an effort to investigate the possible coexistence of mu and delta recognition sites in the same opioid receptor complex. Of the two bivalent ligands (1,2) synthesized, only 1 had substantially greater antinociceptive potency in mice than its monovalent analogues (1a, 1b). Testing of 1, 1a, and 1b in the guinea pig ileum preparation (GPI) revealed a potency profile similar to that found in vivo, whereas no correlation was observed in the mouse vas deferens (MVD). Binding data indicated the same rank-order affinities at delta receptors as the opioid activities in the GPI and in mice. However, mu binding exhibited no relationship with activity. These results are consistent with the simultaneous occupation of mu and delta by a single bivalent ligand 1, but they are also in harmony with the interaction of 1 with an opioid receptor and an accessory binding site. |
| doi_str_mv | 10.1021/jm00394a010 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_81075764</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>81075764</sourcerecordid><originalsourceid>FETCH-LOGICAL-a383t-40a0f76fddfe6c44923f09209bf39e4b0bd879d308ef82c62557c633c2b1a4a93</originalsourceid><addsrcrecordid>eNpt0MtrGzEQBnARUhInzannwB5Ccwjbjh672j2mzsOFQEvs9CpmtVItZ1-R1m3831fBxvSQ08B8P4bhI-QThS8UGP26agF4KRAoHJAJzRikogBxSCYAjKUsZ_yYnISwgugo40fkiAkhJIgJuZ5tKu_qpHJ_sDHdmDTuN3Z1SP66cZn0g8PRJHGRmO7ZDEtsXJfE4VvU_bDsvQkfyQeLTTBnu3lKnu5uF9NZ-vDj_vv0-iFFXvAxFYBgZW7r2ppcC1EybqFkUFaWl0ZUUNWFLGsOhbEF0znLMqlzzjWrKAos-Sn5vL07-P5lbcKoWhe0aRrsTL8OqqAgM5mLCK-2UPs-BG-sGrxr0W8UBfVWmPqvsKjPd2fXVWvqvd01FPOLXY5BY2M9dtqFPZO8BJA0snTLXBjN6z5G_6xyyWWmFj_n6vFmvsi_zX6pafSXW486qFW_9l3s7t0H_wGiBI2n</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>81075764</pqid></control><display><type>article</type><title>Hybrid bivalent ligands with opiate and enkephalin pharmacophores</title><source>MEDLINE</source><source>ACS Publications</source><creator>Portoghese, Philip S ; Larson, D. L ; Ronsisvalle, G ; Schiller, P. W ; Nguyen Thi Mai Dung ; Lemieux, C ; Takemori, A. E</creator><creatorcontrib>Portoghese, Philip S ; Larson, D. L ; Ronsisvalle, G ; Schiller, P. W ; Nguyen Thi Mai Dung ; Lemieux, C ; Takemori, A. E</creatorcontrib><description>Bivalent ligands consisting of oxymorphamine and [D-Glu2]enkephalin pharmacophores linked through a spacer attached to the 6-amino group of the former and D-Glu of the latter were synthesized in an effort to investigate the possible coexistence of mu and delta recognition sites in the same opioid receptor complex. Of the two bivalent ligands (1,2) synthesized, only 1 had substantially greater antinociceptive potency in mice than its monovalent analogues (1a, 1b). Testing of 1, 1a, and 1b in the guinea pig ileum preparation (GPI) revealed a potency profile similar to that found in vivo, whereas no correlation was observed in the mouse vas deferens (MVD). Binding data indicated the same rank-order affinities at delta receptors as the opioid activities in the GPI and in mice. However, mu binding exhibited no relationship with activity. These results are consistent with the simultaneous occupation of mu and delta by a single bivalent ligand 1, but they are also in harmony with the interaction of 1 with an opioid receptor and an accessory binding site.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm00394a010</identifier><identifier>PMID: 2444704</identifier><identifier>CODEN: JMCMAR</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Analgesics - pharmacology ; Animals ; Chemistry ; Enkephalins - metabolism ; Enkephalins - pharmacology ; Exact sciences and technology ; Guinea Pigs ; Hydromorphone - analogs & derivatives ; Ligands ; Male ; Mice ; Muscle, Smooth - drug effects ; Naloxone - pharmacology ; Organic chemistry ; Oxymorphone - analogs & derivatives ; Oxymorphone - metabolism ; Oxymorphone - pharmacology ; Peptides ; Preparations and properties ; Receptors, Opioid - metabolism ; Receptors, Opioid, delta ; Receptors, Opioid, mu</subject><ispartof>Journal of medicinal chemistry, 1987-11, Vol.30 (11), p.1991-1994</ispartof><rights>1988 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a383t-40a0f76fddfe6c44923f09209bf39e4b0bd879d308ef82c62557c633c2b1a4a93</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/jm00394a010$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm00394a010$$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=7390071$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2444704$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Portoghese, Philip S</creatorcontrib><creatorcontrib>Larson, D. L</creatorcontrib><creatorcontrib>Ronsisvalle, G</creatorcontrib><creatorcontrib>Schiller, P. W</creatorcontrib><creatorcontrib>Nguyen Thi Mai Dung</creatorcontrib><creatorcontrib>Lemieux, C</creatorcontrib><creatorcontrib>Takemori, A. E</creatorcontrib><title>Hybrid bivalent ligands with opiate and enkephalin pharmacophores</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>Bivalent ligands consisting of oxymorphamine and [D-Glu2]enkephalin pharmacophores linked through a spacer attached to the 6-amino group of the former and D-Glu of the latter were synthesized in an effort to investigate the possible coexistence of mu and delta recognition sites in the same opioid receptor complex. Of the two bivalent ligands (1,2) synthesized, only 1 had substantially greater antinociceptive potency in mice than its monovalent analogues (1a, 1b). Testing of 1, 1a, and 1b in the guinea pig ileum preparation (GPI) revealed a potency profile similar to that found in vivo, whereas no correlation was observed in the mouse vas deferens (MVD). Binding data indicated the same rank-order affinities at delta receptors as the opioid activities in the GPI and in mice. However, mu binding exhibited no relationship with activity. These results are consistent with the simultaneous occupation of mu and delta by a single bivalent ligand 1, but they are also in harmony with the interaction of 1 with an opioid receptor and an accessory binding site.</description><subject>Analgesics - pharmacology</subject><subject>Animals</subject><subject>Chemistry</subject><subject>Enkephalins - metabolism</subject><subject>Enkephalins - pharmacology</subject><subject>Exact sciences and technology</subject><subject>Guinea Pigs</subject><subject>Hydromorphone - analogs & derivatives</subject><subject>Ligands</subject><subject>Male</subject><subject>Mice</subject><subject>Muscle, Smooth - drug effects</subject><subject>Naloxone - pharmacology</subject><subject>Organic chemistry</subject><subject>Oxymorphone - analogs & derivatives</subject><subject>Oxymorphone - metabolism</subject><subject>Oxymorphone - pharmacology</subject><subject>Peptides</subject><subject>Preparations and properties</subject><subject>Receptors, Opioid - metabolism</subject><subject>Receptors, Opioid, delta</subject><subject>Receptors, Opioid, mu</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1987</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpt0MtrGzEQBnARUhInzannwB5Ccwjbjh672j2mzsOFQEvs9CpmtVItZ1-R1m3831fBxvSQ08B8P4bhI-QThS8UGP26agF4KRAoHJAJzRikogBxSCYAjKUsZ_yYnISwgugo40fkiAkhJIgJuZ5tKu_qpHJ_sDHdmDTuN3Z1SP66cZn0g8PRJHGRmO7ZDEtsXJfE4VvU_bDsvQkfyQeLTTBnu3lKnu5uF9NZ-vDj_vv0-iFFXvAxFYBgZW7r2ppcC1EybqFkUFaWl0ZUUNWFLGsOhbEF0znLMqlzzjWrKAos-Sn5vL07-P5lbcKoWhe0aRrsTL8OqqAgM5mLCK-2UPs-BG-sGrxr0W8UBfVWmPqvsKjPd2fXVWvqvd01FPOLXY5BY2M9dtqFPZO8BJA0snTLXBjN6z5G_6xyyWWmFj_n6vFmvsi_zX6pafSXW486qFW_9l3s7t0H_wGiBI2n</recordid><startdate>19871101</startdate><enddate>19871101</enddate><creator>Portoghese, Philip S</creator><creator>Larson, D. L</creator><creator>Ronsisvalle, G</creator><creator>Schiller, P. W</creator><creator>Nguyen Thi Mai Dung</creator><creator>Lemieux, C</creator><creator>Takemori, A. E</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>19871101</creationdate><title>Hybrid bivalent ligands with opiate and enkephalin pharmacophores</title><author>Portoghese, Philip S ; Larson, D. L ; Ronsisvalle, G ; Schiller, P. W ; Nguyen Thi Mai Dung ; Lemieux, C ; Takemori, A. E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a383t-40a0f76fddfe6c44923f09209bf39e4b0bd879d308ef82c62557c633c2b1a4a93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1987</creationdate><topic>Analgesics - pharmacology</topic><topic>Animals</topic><topic>Chemistry</topic><topic>Enkephalins - metabolism</topic><topic>Enkephalins - pharmacology</topic><topic>Exact sciences and technology</topic><topic>Guinea Pigs</topic><topic>Hydromorphone - analogs & derivatives</topic><topic>Ligands</topic><topic>Male</topic><topic>Mice</topic><topic>Muscle, Smooth - drug effects</topic><topic>Naloxone - pharmacology</topic><topic>Organic chemistry</topic><topic>Oxymorphone - analogs & derivatives</topic><topic>Oxymorphone - metabolism</topic><topic>Oxymorphone - pharmacology</topic><topic>Peptides</topic><topic>Preparations and properties</topic><topic>Receptors, Opioid - metabolism</topic><topic>Receptors, Opioid, delta</topic><topic>Receptors, Opioid, mu</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Portoghese, Philip S</creatorcontrib><creatorcontrib>Larson, D. L</creatorcontrib><creatorcontrib>Ronsisvalle, G</creatorcontrib><creatorcontrib>Schiller, P. W</creatorcontrib><creatorcontrib>Nguyen Thi Mai Dung</creatorcontrib><creatorcontrib>Lemieux, C</creatorcontrib><creatorcontrib>Takemori, A. E</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>Portoghese, Philip S</au><au>Larson, D. L</au><au>Ronsisvalle, G</au><au>Schiller, P. W</au><au>Nguyen Thi Mai Dung</au><au>Lemieux, C</au><au>Takemori, A. E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hybrid bivalent ligands with opiate and enkephalin pharmacophores</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>1987-11-01</date><risdate>1987</risdate><volume>30</volume><issue>11</issue><spage>1991</spage><epage>1994</epage><pages>1991-1994</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><abstract>Bivalent ligands consisting of oxymorphamine and [D-Glu2]enkephalin pharmacophores linked through a spacer attached to the 6-amino group of the former and D-Glu of the latter were synthesized in an effort to investigate the possible coexistence of mu and delta recognition sites in the same opioid receptor complex. Of the two bivalent ligands (1,2) synthesized, only 1 had substantially greater antinociceptive potency in mice than its monovalent analogues (1a, 1b). Testing of 1, 1a, and 1b in the guinea pig ileum preparation (GPI) revealed a potency profile similar to that found in vivo, whereas no correlation was observed in the mouse vas deferens (MVD). Binding data indicated the same rank-order affinities at delta receptors as the opioid activities in the GPI and in mice. However, mu binding exhibited no relationship with activity. These results are consistent with the simultaneous occupation of mu and delta by a single bivalent ligand 1, but they are also in harmony with the interaction of 1 with an opioid receptor and an accessory binding site.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>2444704</pmid><doi>10.1021/jm00394a010</doi><tpages>4</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-2623 |
| ispartof | Journal of medicinal chemistry, 1987-11, Vol.30 (11), p.1991-1994 |
| issn | 0022-2623 1520-4804 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_81075764 |
| source | MEDLINE; ACS Publications |
| subjects | Analgesics - pharmacology Animals Chemistry Enkephalins - metabolism Enkephalins - pharmacology Exact sciences and technology Guinea Pigs Hydromorphone - analogs & derivatives Ligands Male Mice Muscle, Smooth - drug effects Naloxone - pharmacology Organic chemistry Oxymorphone - analogs & derivatives Oxymorphone - metabolism Oxymorphone - pharmacology Peptides Preparations and properties Receptors, Opioid - metabolism Receptors, Opioid, delta Receptors, Opioid, mu |
| title | Hybrid bivalent ligands with opiate and enkephalin pharmacophores |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-04T16%3A57%3A36IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Hybrid%20bivalent%20ligands%20with%20opiate%20and%20enkephalin%20pharmacophores&rft.jtitle=Journal%20of%20medicinal%20chemistry&rft.au=Portoghese,%20Philip%20S&rft.date=1987-11-01&rft.volume=30&rft.issue=11&rft.spage=1991&rft.epage=1994&rft.pages=1991-1994&rft.issn=0022-2623&rft.eissn=1520-4804&rft.coden=JMCMAR&rft_id=info:doi/10.1021/jm00394a010&rft_dat=%3Cproquest_cross%3E81075764%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=81075764&rft_id=info:pmid/2444704&rfr_iscdi=true |