Semirational Design of (North)-Methanocarba Nucleosides as Dual Acting A1 and A3 Adenosine Receptor Agonists: Novel Prototypes for Cardioprotection
Ring-constrained adenosine analogues have been designed to act as dual agonists at tissue-protective A1 and A3 adenosine receptors (ARs). 9-Ribosides transformed into the ring-constrained (N)-methanocarba-2-chloro-5‘-uronamides consistently lost affinity at A1/A2AARs and gained at A3AR. Among 9-ribo...
Gespeichert in:
| Veröffentlicht in: | Journal of medicinal chemistry 2005-12, Vol.48 (26), p.8103-8107 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 8107 |
|---|---|
| container_issue | 26 |
| container_start_page | 8103 |
| container_title | Journal of medicinal chemistry |
| container_volume | 48 |
| creator | Jacobson, Kenneth A Gao, Zhan-Guo Tchilibon, Susanna Duong, Heng T Joshi, Bhalchandra V Sonin, Dmitry Liang, Bruce T |
| description | Ring-constrained adenosine analogues have been designed to act as dual agonists at tissue-protective A1 and A3 adenosine receptors (ARs). 9-Ribosides transformed into the ring-constrained (N)-methanocarba-2-chloro-5‘-uronamides consistently lost affinity at A1/A2AARs and gained at A3AR. Among 9-riboside derivatives, only N 6-cyclopentyl and 7-norbornyl moieties were extrapolated for mixed A1/A3 selectivity and rat/human A3AR equipotency. Consequently, 2 was balanced in affinity and potency at A1/A3ARs as envisioned and dramatically protected in an intact heart model of global ischemia and reperfusion. |
| doi_str_mv | 10.1021/jm050726b |
| format | Article |
| fullrecord | <record><control><sourceid>acs_pasca</sourceid><recordid>TN_cdi_pascalfrancis_primary_17385348</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>a232152379</sourcerecordid><originalsourceid>FETCH-LOGICAL-a203b-100b56863cf045529d524da42cb6a0b3c60ab754fff1dccf969eb71bfd80dac93</originalsourceid><addsrcrecordid>eNpFkc9u1DAQxi0EEkvhwBv4ggSHlLGdOFluYVsKqCwVW7ha439bL1k7srOovXHlBXhAnoRUReU00sxvPs03HyHPGRwz4Oz1bg8NtFzqB2TBGg5V3UH9kCwAOK-45OIxeVLKDgAE42JBfm_cPmScQoo40BNXwjbS5OnLdcrT1avqk5uuMCaDWSNdH8zgUgnWFYqFnhzmld5MIW5pzyhGS3tBe-vizERHvzjjxill2m9TDGUqb_78_EXX6Ycb6EVOU5puxlnJz8QKsw1pnJvO3N7ylDzyOBT37F89Il_fnV6u3lfnn88-rPrzCjkIXTEA3chOCuOhbhq-tA2vLdbcaImghZGAum1q7z2zxvilXDrdMu1tBxbNUhyRF3e6IxaDg88YTShqzGGP-UaxVnSNqLuZq-642Ya7vp9j_q5kK9pGXV5s1LePm1a8hTMl_-uiKWqXDnn-blEM1G1I6j4k8Rdkm4Xh</addsrcrecordid><sourcetype>Index Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Semirational Design of (North)-Methanocarba Nucleosides as Dual Acting A1 and A3 Adenosine Receptor Agonists: Novel Prototypes for Cardioprotection</title><source>ACS Journals: American Chemical Society Web Editions</source><creator>Jacobson, Kenneth A ; Gao, Zhan-Guo ; Tchilibon, Susanna ; Duong, Heng T ; Joshi, Bhalchandra V ; Sonin, Dmitry ; Liang, Bruce T</creator><creatorcontrib>Jacobson, Kenneth A ; Gao, Zhan-Guo ; Tchilibon, Susanna ; Duong, Heng T ; Joshi, Bhalchandra V ; Sonin, Dmitry ; Liang, Bruce T</creatorcontrib><description>Ring-constrained adenosine analogues have been designed to act as dual agonists at tissue-protective A1 and A3 adenosine receptors (ARs). 9-Ribosides transformed into the ring-constrained (N)-methanocarba-2-chloro-5‘-uronamides consistently lost affinity at A1/A2AARs and gained at A3AR. Among 9-riboside derivatives, only N 6-cyclopentyl and 7-norbornyl moieties were extrapolated for mixed A1/A3 selectivity and rat/human A3AR equipotency. Consequently, 2 was balanced in affinity and potency at A1/A3ARs as envisioned and dramatically protected in an intact heart model of global ischemia and reperfusion.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm050726b</identifier><identifier>CODEN: JMCMAR</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Biological and medical sciences ; Cardiovascular system ; Medical sciences ; Miscellaneous ; Neuropharmacology ; Neurotransmitters. Neurotransmission. Receptors ; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems ; Pharmacology. Drug treatments</subject><ispartof>Journal of medicinal chemistry, 2005-12, Vol.48 (26), p.8103-8107</ispartof><rights>Copyright © 2005 American Chemical Society</rights><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jm050726b$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm050726b$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17385348$$DView record in Pascal Francis$$Hfree_for_read</backlink></links><search><creatorcontrib>Jacobson, Kenneth A</creatorcontrib><creatorcontrib>Gao, Zhan-Guo</creatorcontrib><creatorcontrib>Tchilibon, Susanna</creatorcontrib><creatorcontrib>Duong, Heng T</creatorcontrib><creatorcontrib>Joshi, Bhalchandra V</creatorcontrib><creatorcontrib>Sonin, Dmitry</creatorcontrib><creatorcontrib>Liang, Bruce T</creatorcontrib><title>Semirational Design of (North)-Methanocarba Nucleosides as Dual Acting A1 and A3 Adenosine Receptor Agonists: Novel Prototypes for Cardioprotection</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>Ring-constrained adenosine analogues have been designed to act as dual agonists at tissue-protective A1 and A3 adenosine receptors (ARs). 9-Ribosides transformed into the ring-constrained (N)-methanocarba-2-chloro-5‘-uronamides consistently lost affinity at A1/A2AARs and gained at A3AR. Among 9-riboside derivatives, only N 6-cyclopentyl and 7-norbornyl moieties were extrapolated for mixed A1/A3 selectivity and rat/human A3AR equipotency. Consequently, 2 was balanced in affinity and potency at A1/A3ARs as envisioned and dramatically protected in an intact heart model of global ischemia and reperfusion.</description><subject>Biological and medical sciences</subject><subject>Cardiovascular system</subject><subject>Medical sciences</subject><subject>Miscellaneous</subject><subject>Neuropharmacology</subject><subject>Neurotransmitters. Neurotransmission. Receptors</subject><subject>Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems</subject><subject>Pharmacology. Drug treatments</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><recordid>eNpFkc9u1DAQxi0EEkvhwBv4ggSHlLGdOFluYVsKqCwVW7ha439bL1k7srOovXHlBXhAnoRUReU00sxvPs03HyHPGRwz4Oz1bg8NtFzqB2TBGg5V3UH9kCwAOK-45OIxeVLKDgAE42JBfm_cPmScQoo40BNXwjbS5OnLdcrT1avqk5uuMCaDWSNdH8zgUgnWFYqFnhzmld5MIW5pzyhGS3tBe-vizERHvzjjxill2m9TDGUqb_78_EXX6Ycb6EVOU5puxlnJz8QKsw1pnJvO3N7ylDzyOBT37F89Il_fnV6u3lfnn88-rPrzCjkIXTEA3chOCuOhbhq-tA2vLdbcaImghZGAum1q7z2zxvilXDrdMu1tBxbNUhyRF3e6IxaDg88YTShqzGGP-UaxVnSNqLuZq-642Ya7vp9j_q5kK9pGXV5s1LePm1a8hTMl_-uiKWqXDnn-blEM1G1I6j4k8Rdkm4Xh</recordid><startdate>20051229</startdate><enddate>20051229</enddate><creator>Jacobson, Kenneth A</creator><creator>Gao, Zhan-Guo</creator><creator>Tchilibon, Susanna</creator><creator>Duong, Heng T</creator><creator>Joshi, Bhalchandra V</creator><creator>Sonin, Dmitry</creator><creator>Liang, Bruce T</creator><general>American Chemical Society</general><scope>BSCLL</scope><scope>IQODW</scope></search><sort><creationdate>20051229</creationdate><title>Semirational Design of (North)-Methanocarba Nucleosides as Dual Acting A1 and A3 Adenosine Receptor Agonists: Novel Prototypes for Cardioprotection</title><author>Jacobson, Kenneth A ; Gao, Zhan-Guo ; Tchilibon, Susanna ; Duong, Heng T ; Joshi, Bhalchandra V ; Sonin, Dmitry ; Liang, Bruce T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a203b-100b56863cf045529d524da42cb6a0b3c60ab754fff1dccf969eb71bfd80dac93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Biological and medical sciences</topic><topic>Cardiovascular system</topic><topic>Medical sciences</topic><topic>Miscellaneous</topic><topic>Neuropharmacology</topic><topic>Neurotransmitters. Neurotransmission. Receptors</topic><topic>Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems</topic><topic>Pharmacology. Drug treatments</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jacobson, Kenneth A</creatorcontrib><creatorcontrib>Gao, Zhan-Guo</creatorcontrib><creatorcontrib>Tchilibon, Susanna</creatorcontrib><creatorcontrib>Duong, Heng T</creatorcontrib><creatorcontrib>Joshi, Bhalchandra V</creatorcontrib><creatorcontrib>Sonin, Dmitry</creatorcontrib><creatorcontrib>Liang, Bruce T</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jacobson, Kenneth A</au><au>Gao, Zhan-Guo</au><au>Tchilibon, Susanna</au><au>Duong, Heng T</au><au>Joshi, Bhalchandra V</au><au>Sonin, Dmitry</au><au>Liang, Bruce T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Semirational Design of (North)-Methanocarba Nucleosides as Dual Acting A1 and A3 Adenosine Receptor Agonists: Novel Prototypes for Cardioprotection</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>2005-12-29</date><risdate>2005</risdate><volume>48</volume><issue>26</issue><spage>8103</spage><epage>8107</epage><pages>8103-8107</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><abstract>Ring-constrained adenosine analogues have been designed to act as dual agonists at tissue-protective A1 and A3 adenosine receptors (ARs). 9-Ribosides transformed into the ring-constrained (N)-methanocarba-2-chloro-5‘-uronamides consistently lost affinity at A1/A2AARs and gained at A3AR. Among 9-riboside derivatives, only N 6-cyclopentyl and 7-norbornyl moieties were extrapolated for mixed A1/A3 selectivity and rat/human A3AR equipotency. Consequently, 2 was balanced in affinity and potency at A1/A3ARs as envisioned and dramatically protected in an intact heart model of global ischemia and reperfusion.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><doi>10.1021/jm050726b</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-2623 |
| ispartof | Journal of medicinal chemistry, 2005-12, Vol.48 (26), p.8103-8107 |
| issn | 0022-2623 1520-4804 |
| language | eng |
| recordid | cdi_pascalfrancis_primary_17385348 |
| source | ACS Journals: American Chemical Society Web Editions |
| subjects | Biological and medical sciences Cardiovascular system Medical sciences Miscellaneous Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems Pharmacology. Drug treatments |
| title | Semirational Design of (North)-Methanocarba Nucleosides as Dual Acting A1 and A3 Adenosine Receptor Agonists: Novel Prototypes for Cardioprotection |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T09%3A51%3A33IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-acs_pasca&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Semirational%20Design%20of%20(North)-Methanocarba%20Nucleosides%20as%20Dual%20Acting%20A1%20and%20A3%20Adenosine%20Receptor%20Agonists:%E2%80%89%20Novel%20Prototypes%20for%20Cardioprotection&rft.jtitle=Journal%20of%20medicinal%20chemistry&rft.au=Jacobson,%20Kenneth%20A&rft.date=2005-12-29&rft.volume=48&rft.issue=26&rft.spage=8103&rft.epage=8107&rft.pages=8103-8107&rft.issn=0022-2623&rft.eissn=1520-4804&rft.coden=JMCMAR&rft_id=info:doi/10.1021/jm050726b&rft_dat=%3Cacs_pasca%3Ea232152379%3C/acs_pasca%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/&rfr_iscdi=true |