Selective CB2 receptor agonists. Part 2: Structure–activity relationship studies and optimization of proline-based compounds
[Display omitted] Through a ligand-based pharmacophore model (S)-proline based compounds were identified as potent cannabinoid receptor 2 (CB2) agonists with high selectivity over the cannabinoid receptor 1 (CB1). Structure–activity relationship investigations for this compound class lead to oxo-pro...
Gespeichert in:
| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2015-02, Vol.25 (3), p.581-586 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 586 |
|---|---|
| container_issue | 3 |
| container_start_page | 581 |
| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 25 |
| creator | Riether, Doris Zindell, Renee Wu, Lifen Betageri, Raj Jenkins, James E. Khor, Someina Berry, Angela K. Hickey, Eugene R. Ermann, Monika Albrecht, Claudia Ceci, Angelo Gemkow, Mark J. Nagaraja, Nelamangala V. Romig, Helmut Sauer, Achim Thomson, David S. |
| description | [Display omitted]
Through a ligand-based pharmacophore model (S)-proline based compounds were identified as potent cannabinoid receptor 2 (CB2) agonists with high selectivity over the cannabinoid receptor 1 (CB1). Structure–activity relationship investigations for this compound class lead to oxo-proline compounds 21 and 22 which combine an impressive CB1 selectivity profile with good pharmacokinetic properties. In a streptozotocin induced diabetic neuropathy model, 22 demonstrated a dose-dependent reversal of mechanical hyperalgesia. |
| doi_str_mv | 10.1016/j.bmcl.2014.12.019 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1660394123</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0960894X1401316X</els_id><sourcerecordid>1652419738</sourcerecordid><originalsourceid>FETCH-LOGICAL-c414t-116f1d8df46f88f8235899351faa29d358612145b5417caf143a1e19b3d6d0613</originalsourceid><addsrcrecordid>eNqNkc9qFTEUh4Mo9lp9AReSpZsZczKZdCJu7MU_hUKFKrgLmeSM5jIzGZNMoV2I7-Ab-iTmeqtL6Soc8v1-HM5HyFNgNTCQL3Z1P9mx5gxEDbxmoO6RDQgpqkaw9j7ZMCVZ1Snx-Yg8SmnHCsiEeEiOeNu2kim-Id8vcUSb_RXS7SmnES0uOURqvoTZp5xq-sHETPlLepnjavMa8dePn2af8Pm68KPJPszpq19oyqvzmKiZHQ1L9pO_-fNJw0CXGEY_Y9WbhI7aMC1hnV16TB4MZkz45PY9Jp_evvm4fV-dX7w7274-r6wAkSsAOYDr3CDk0HVDx5u2U6ppYTCGK1cmCRxE27cCTqwZQDQGEFTfOOmYhOaYPD_0lj2-rZiynnyyOI5mxrAmDVKyRgngzR3QlgtQJ01XUH5AbQwpRRz0Ev1k4rUGpveK9E7vFem9Ig1cF0Ul9Oy2f-0ndP8if50U4NUBwHKQK49RJ-txtuh80ZO1C_5__b8BzkOkFg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1652419738</pqid></control><display><type>article</type><title>Selective CB2 receptor agonists. Part 2: Structure–activity relationship studies and optimization of proline-based compounds</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Riether, Doris ; Zindell, Renee ; Wu, Lifen ; Betageri, Raj ; Jenkins, James E. ; Khor, Someina ; Berry, Angela K. ; Hickey, Eugene R. ; Ermann, Monika ; Albrecht, Claudia ; Ceci, Angelo ; Gemkow, Mark J. ; Nagaraja, Nelamangala V. ; Romig, Helmut ; Sauer, Achim ; Thomson, David S.</creator><creatorcontrib>Riether, Doris ; Zindell, Renee ; Wu, Lifen ; Betageri, Raj ; Jenkins, James E. ; Khor, Someina ; Berry, Angela K. ; Hickey, Eugene R. ; Ermann, Monika ; Albrecht, Claudia ; Ceci, Angelo ; Gemkow, Mark J. ; Nagaraja, Nelamangala V. ; Romig, Helmut ; Sauer, Achim ; Thomson, David S.</creatorcontrib><description>[Display omitted]
Through a ligand-based pharmacophore model (S)-proline based compounds were identified as potent cannabinoid receptor 2 (CB2) agonists with high selectivity over the cannabinoid receptor 1 (CB1). Structure–activity relationship investigations for this compound class lead to oxo-proline compounds 21 and 22 which combine an impressive CB1 selectivity profile with good pharmacokinetic properties. In a streptozotocin induced diabetic neuropathy model, 22 demonstrated a dose-dependent reversal of mechanical hyperalgesia.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2014.12.019</identifier><identifier>PMID: 25556092</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Animals ; Cannabinoid receptor 2 (CB2) ; Diabetic Neuropathies - chemically induced ; Diabetic Neuropathies - drug therapy ; Half-Life ; Humans ; Isoxazoles - chemistry ; Isoxazoles - pharmacokinetics ; Isoxazoles - therapeutic use ; Ligands ; Male ; Metabolic stability ; Microsomes, Liver - metabolism ; Pharmacokinetic properties ; Proline ; Proline - chemistry ; Proline - pharmacokinetics ; Proline - therapeutic use ; Protein Binding ; Pyrrolidonecarboxylic Acid - analogs & derivatives ; Pyrrolidonecarboxylic Acid - chemistry ; Pyrrolidonecarboxylic Acid - pharmacokinetics ; Pyrrolidonecarboxylic Acid - therapeutic use ; Rats ; Rats, Wistar ; Receptor, Cannabinoid, CB1 - agonists ; Receptor, Cannabinoid, CB1 - metabolism ; Receptor, Cannabinoid, CB2 - agonists ; Receptor, Cannabinoid, CB2 - metabolism ; Solubility ; Structure-Activity Relationship</subject><ispartof>Bioorganic & medicinal chemistry letters, 2015-02, Vol.25 (3), p.581-586</ispartof><rights>2014 Elsevier Ltd</rights><rights>Copyright © 2014 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c414t-116f1d8df46f88f8235899351faa29d358612145b5417caf143a1e19b3d6d0613</citedby><cites>FETCH-LOGICAL-c414t-116f1d8df46f88f8235899351faa29d358612145b5417caf143a1e19b3d6d0613</cites><orcidid>0000-0002-8535-2501</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bmcl.2014.12.019$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25556092$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Riether, Doris</creatorcontrib><creatorcontrib>Zindell, Renee</creatorcontrib><creatorcontrib>Wu, Lifen</creatorcontrib><creatorcontrib>Betageri, Raj</creatorcontrib><creatorcontrib>Jenkins, James E.</creatorcontrib><creatorcontrib>Khor, Someina</creatorcontrib><creatorcontrib>Berry, Angela K.</creatorcontrib><creatorcontrib>Hickey, Eugene R.</creatorcontrib><creatorcontrib>Ermann, Monika</creatorcontrib><creatorcontrib>Albrecht, Claudia</creatorcontrib><creatorcontrib>Ceci, Angelo</creatorcontrib><creatorcontrib>Gemkow, Mark J.</creatorcontrib><creatorcontrib>Nagaraja, Nelamangala V.</creatorcontrib><creatorcontrib>Romig, Helmut</creatorcontrib><creatorcontrib>Sauer, Achim</creatorcontrib><creatorcontrib>Thomson, David S.</creatorcontrib><title>Selective CB2 receptor agonists. Part 2: Structure–activity relationship studies and optimization of proline-based compounds</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>[Display omitted]
Through a ligand-based pharmacophore model (S)-proline based compounds were identified as potent cannabinoid receptor 2 (CB2) agonists with high selectivity over the cannabinoid receptor 1 (CB1). Structure–activity relationship investigations for this compound class lead to oxo-proline compounds 21 and 22 which combine an impressive CB1 selectivity profile with good pharmacokinetic properties. In a streptozotocin induced diabetic neuropathy model, 22 demonstrated a dose-dependent reversal of mechanical hyperalgesia.</description><subject>Animals</subject><subject>Cannabinoid receptor 2 (CB2)</subject><subject>Diabetic Neuropathies - chemically induced</subject><subject>Diabetic Neuropathies - drug therapy</subject><subject>Half-Life</subject><subject>Humans</subject><subject>Isoxazoles - chemistry</subject><subject>Isoxazoles - pharmacokinetics</subject><subject>Isoxazoles - therapeutic use</subject><subject>Ligands</subject><subject>Male</subject><subject>Metabolic stability</subject><subject>Microsomes, Liver - metabolism</subject><subject>Pharmacokinetic properties</subject><subject>Proline</subject><subject>Proline - chemistry</subject><subject>Proline - pharmacokinetics</subject><subject>Proline - therapeutic use</subject><subject>Protein Binding</subject><subject>Pyrrolidonecarboxylic Acid - analogs & derivatives</subject><subject>Pyrrolidonecarboxylic Acid - chemistry</subject><subject>Pyrrolidonecarboxylic Acid - pharmacokinetics</subject><subject>Pyrrolidonecarboxylic Acid - therapeutic use</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Receptor, Cannabinoid, CB1 - agonists</subject><subject>Receptor, Cannabinoid, CB1 - metabolism</subject><subject>Receptor, Cannabinoid, CB2 - agonists</subject><subject>Receptor, Cannabinoid, CB2 - metabolism</subject><subject>Solubility</subject><subject>Structure-Activity Relationship</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc9qFTEUh4Mo9lp9AReSpZsZczKZdCJu7MU_hUKFKrgLmeSM5jIzGZNMoV2I7-Ab-iTmeqtL6Soc8v1-HM5HyFNgNTCQL3Z1P9mx5gxEDbxmoO6RDQgpqkaw9j7ZMCVZ1Snx-Yg8SmnHCsiEeEiOeNu2kim-Id8vcUSb_RXS7SmnES0uOURqvoTZp5xq-sHETPlLepnjavMa8dePn2af8Pm68KPJPszpq19oyqvzmKiZHQ1L9pO_-fNJw0CXGEY_Y9WbhI7aMC1hnV16TB4MZkz45PY9Jp_evvm4fV-dX7w7274-r6wAkSsAOYDr3CDk0HVDx5u2U6ppYTCGK1cmCRxE27cCTqwZQDQGEFTfOOmYhOaYPD_0lj2-rZiynnyyOI5mxrAmDVKyRgngzR3QlgtQJ01XUH5AbQwpRRz0Ev1k4rUGpveK9E7vFem9Ig1cF0Ul9Oy2f-0ndP8if50U4NUBwHKQK49RJ-txtuh80ZO1C_5__b8BzkOkFg</recordid><startdate>20150201</startdate><enddate>20150201</enddate><creator>Riether, Doris</creator><creator>Zindell, Renee</creator><creator>Wu, Lifen</creator><creator>Betageri, Raj</creator><creator>Jenkins, James E.</creator><creator>Khor, Someina</creator><creator>Berry, Angela K.</creator><creator>Hickey, Eugene R.</creator><creator>Ermann, Monika</creator><creator>Albrecht, Claudia</creator><creator>Ceci, Angelo</creator><creator>Gemkow, Mark J.</creator><creator>Nagaraja, Nelamangala V.</creator><creator>Romig, Helmut</creator><creator>Sauer, Achim</creator><creator>Thomson, David S.</creator><general>Elsevier Ltd</general><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><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><orcidid>https://orcid.org/0000-0002-8535-2501</orcidid></search><sort><creationdate>20150201</creationdate><title>Selective CB2 receptor agonists. Part 2: Structure–activity relationship studies and optimization of proline-based compounds</title><author>Riether, Doris ; Zindell, Renee ; Wu, Lifen ; Betageri, Raj ; Jenkins, James E. ; Khor, Someina ; Berry, Angela K. ; Hickey, Eugene R. ; Ermann, Monika ; Albrecht, Claudia ; Ceci, Angelo ; Gemkow, Mark J. ; Nagaraja, Nelamangala V. ; Romig, Helmut ; Sauer, Achim ; Thomson, David S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c414t-116f1d8df46f88f8235899351faa29d358612145b5417caf143a1e19b3d6d0613</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Cannabinoid receptor 2 (CB2)</topic><topic>Diabetic Neuropathies - chemically induced</topic><topic>Diabetic Neuropathies - drug therapy</topic><topic>Half-Life</topic><topic>Humans</topic><topic>Isoxazoles - chemistry</topic><topic>Isoxazoles - pharmacokinetics</topic><topic>Isoxazoles - therapeutic use</topic><topic>Ligands</topic><topic>Male</topic><topic>Metabolic stability</topic><topic>Microsomes, Liver - metabolism</topic><topic>Pharmacokinetic properties</topic><topic>Proline</topic><topic>Proline - chemistry</topic><topic>Proline - pharmacokinetics</topic><topic>Proline - therapeutic use</topic><topic>Protein Binding</topic><topic>Pyrrolidonecarboxylic Acid - analogs & derivatives</topic><topic>Pyrrolidonecarboxylic Acid - chemistry</topic><topic>Pyrrolidonecarboxylic Acid - pharmacokinetics</topic><topic>Pyrrolidonecarboxylic Acid - therapeutic use</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Receptor, Cannabinoid, CB1 - agonists</topic><topic>Receptor, Cannabinoid, CB1 - metabolism</topic><topic>Receptor, Cannabinoid, CB2 - agonists</topic><topic>Receptor, Cannabinoid, CB2 - metabolism</topic><topic>Solubility</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Riether, Doris</creatorcontrib><creatorcontrib>Zindell, Renee</creatorcontrib><creatorcontrib>Wu, Lifen</creatorcontrib><creatorcontrib>Betageri, Raj</creatorcontrib><creatorcontrib>Jenkins, James E.</creatorcontrib><creatorcontrib>Khor, Someina</creatorcontrib><creatorcontrib>Berry, Angela K.</creatorcontrib><creatorcontrib>Hickey, Eugene R.</creatorcontrib><creatorcontrib>Ermann, Monika</creatorcontrib><creatorcontrib>Albrecht, Claudia</creatorcontrib><creatorcontrib>Ceci, Angelo</creatorcontrib><creatorcontrib>Gemkow, Mark J.</creatorcontrib><creatorcontrib>Nagaraja, Nelamangala V.</creatorcontrib><creatorcontrib>Romig, Helmut</creatorcontrib><creatorcontrib>Sauer, Achim</creatorcontrib><creatorcontrib>Thomson, David S.</creatorcontrib><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><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Riether, Doris</au><au>Zindell, Renee</au><au>Wu, Lifen</au><au>Betageri, Raj</au><au>Jenkins, James E.</au><au>Khor, Someina</au><au>Berry, Angela K.</au><au>Hickey, Eugene R.</au><au>Ermann, Monika</au><au>Albrecht, Claudia</au><au>Ceci, Angelo</au><au>Gemkow, Mark J.</au><au>Nagaraja, Nelamangala V.</au><au>Romig, Helmut</au><au>Sauer, Achim</au><au>Thomson, David S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Selective CB2 receptor agonists. Part 2: Structure–activity relationship studies and optimization of proline-based compounds</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2015-02-01</date><risdate>2015</risdate><volume>25</volume><issue>3</issue><spage>581</spage><epage>586</epage><pages>581-586</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>[Display omitted]
Through a ligand-based pharmacophore model (S)-proline based compounds were identified as potent cannabinoid receptor 2 (CB2) agonists with high selectivity over the cannabinoid receptor 1 (CB1). Structure–activity relationship investigations for this compound class lead to oxo-proline compounds 21 and 22 which combine an impressive CB1 selectivity profile with good pharmacokinetic properties. In a streptozotocin induced diabetic neuropathy model, 22 demonstrated a dose-dependent reversal of mechanical hyperalgesia.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>25556092</pmid><doi>10.1016/j.bmcl.2014.12.019</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0002-8535-2501</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2015-02, Vol.25 (3), p.581-586 |
| issn | 0960-894X 1464-3405 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1660394123 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animals Cannabinoid receptor 2 (CB2) Diabetic Neuropathies - chemically induced Diabetic Neuropathies - drug therapy Half-Life Humans Isoxazoles - chemistry Isoxazoles - pharmacokinetics Isoxazoles - therapeutic use Ligands Male Metabolic stability Microsomes, Liver - metabolism Pharmacokinetic properties Proline Proline - chemistry Proline - pharmacokinetics Proline - therapeutic use Protein Binding Pyrrolidonecarboxylic Acid - analogs & derivatives Pyrrolidonecarboxylic Acid - chemistry Pyrrolidonecarboxylic Acid - pharmacokinetics Pyrrolidonecarboxylic Acid - therapeutic use Rats Rats, Wistar Receptor, Cannabinoid, CB1 - agonists Receptor, Cannabinoid, CB1 - metabolism Receptor, Cannabinoid, CB2 - agonists Receptor, Cannabinoid, CB2 - metabolism Solubility Structure-Activity Relationship |
| title | Selective CB2 receptor agonists. Part 2: Structure–activity relationship studies and optimization of proline-based compounds |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-19T08%3A02%3A59IST&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=Selective%20CB2%20receptor%20agonists.%20Part%202:%20Structure%E2%80%93activity%20relationship%20studies%20and%20optimization%20of%20proline-based%20compounds&rft.jtitle=Bioorganic%20&%20medicinal%20chemistry%20letters&rft.au=Riether,%20Doris&rft.date=2015-02-01&rft.volume=25&rft.issue=3&rft.spage=581&rft.epage=586&rft.pages=581-586&rft.issn=0960-894X&rft.eissn=1464-3405&rft_id=info:doi/10.1016/j.bmcl.2014.12.019&rft_dat=%3Cproquest_cross%3E1652419738%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=1652419738&rft_id=info:pmid/25556092&rft_els_id=S0960894X1401316X&rfr_iscdi=true |