N6-(Arylalkyl)adenosines. Identification of N6-(9-fluorenylmethyl)adenosine as a highly potent agonist for the adenosine A2 receptor
Several N6-(arylalkyl)adenosines related to N6-benzyladenosine were synthesized, and their A1 and A2 adenosine receptor binding affinities were determined. The annulated derivative N6-(1-naphthylmethyl)adenosine resulted in a very potent A2 agonist (A1 Ki = 24 nM, A2 Ki = 9.1 nM), whereas N6-(9-anth...
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| Veröffentlicht in: | Journal of medicinal chemistry 1988-01, Vol.31 (1), p.271-273 |
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| container_title | Journal of medicinal chemistry |
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| creator | Trivedi, B. K Bristol, J. A Bruns, R. F Haleen, S. J Steffen, R. P |
| description | Several N6-(arylalkyl)adenosines related to N6-benzyladenosine were synthesized, and their A1 and A2 adenosine receptor binding affinities were determined. The annulated derivative N6-(1-naphthylmethyl)adenosine resulted in a very potent A2 agonist (A1 Ki = 24 nM, A2 Ki = 9.1 nM), whereas N6-(9-anthracenylmethyl)adenosine was virtually inactive (A1 Ki = 9,000 nM, A2 Ki = 29,000 nM). Interestingly, the structurally similar N6-(9-fluorenylmethyl)adenosine was the most potent A2 agonist reported to date, with a Ki of 4.9 nM in A2 binding and 5.1 nM in A1 binding. The homologues N6-9-fluorenyladenosine and N6-[2-(9-fluorenyl)ethyl]adenosine showed little or no activity at either adenosine receptor. Effects of these agents on heart rate and coronary flow in the isolated rat heart paralleled their A1 and A2 binding affinities, respectively. These data suggest that for high affinity at the A2 receptor a planar hydrophobic function at a certain distance and angle from the N6 nitrogen is required. |
| doi_str_mv | 10.1021/jm00396a044 |
| format | Article |
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Identification of N6-(9-fluorenylmethyl)adenosine as a highly potent agonist for the adenosine A2 receptor</title><source>MEDLINE</source><source>ACS Publications</source><creator>Trivedi, B. K ; Bristol, J. A ; Bruns, R. F ; Haleen, S. J ; Steffen, R. P</creator><creatorcontrib>Trivedi, B. K ; Bristol, J. A ; Bruns, R. F ; Haleen, S. J ; Steffen, R. P</creatorcontrib><description>Several N6-(arylalkyl)adenosines related to N6-benzyladenosine were synthesized, and their A1 and A2 adenosine receptor binding affinities were determined. The annulated derivative N6-(1-naphthylmethyl)adenosine resulted in a very potent A2 agonist (A1 Ki = 24 nM, A2 Ki = 9.1 nM), whereas N6-(9-anthracenylmethyl)adenosine was virtually inactive (A1 Ki = 9,000 nM, A2 Ki = 29,000 nM). Interestingly, the structurally similar N6-(9-fluorenylmethyl)adenosine was the most potent A2 agonist reported to date, with a Ki of 4.9 nM in A2 binding and 5.1 nM in A1 binding. The homologues N6-9-fluorenyladenosine and N6-[2-(9-fluorenyl)ethyl]adenosine showed little or no activity at either adenosine receptor. Effects of these agents on heart rate and coronary flow in the isolated rat heart paralleled their A1 and A2 binding affinities, respectively. These data suggest that for high affinity at the A2 receptor a planar hydrophobic function at a certain distance and angle from the N6 nitrogen is required.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm00396a044</identifier><identifier>PMID: 3336027</identifier><identifier>CODEN: JMCMAR</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Adenosine - analogs & derivatives ; Adenosine - chemical synthesis ; Adenosine - metabolism ; Animals ; Brain - metabolism ; Carbohydrates. Nucleosides and nucleotides ; Cell Membrane - metabolism ; Chemistry ; Coronary Circulation - drug effects ; Exact sciences and technology ; Fluorenes - chemical synthesis ; Fluorenes - metabolism ; Heart Rate - drug effects ; In Vitro Techniques ; Indicators and Reagents ; Kinetics ; Nucleosides, nucleotides and oligonucleotides ; Organic chemistry ; Preparations and properties ; Rats ; Receptors, Purinergic - metabolism ; Structure-Activity Relationship</subject><ispartof>Journal of medicinal chemistry, 1988-01, Vol.31 (1), p.271-273</ispartof><rights>1988 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a315t-bc183c567eb008e2570c0cc7495b20dd8ad6d84a9ad25af8cd2748a6f751b843</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/jm00396a044$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm00396a044$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2765,4024,27076,27923,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=7484828$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/3336027$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Trivedi, B. K</creatorcontrib><creatorcontrib>Bristol, J. A</creatorcontrib><creatorcontrib>Bruns, R. F</creatorcontrib><creatorcontrib>Haleen, S. J</creatorcontrib><creatorcontrib>Steffen, R. P</creatorcontrib><title>N6-(Arylalkyl)adenosines. Identification of N6-(9-fluorenylmethyl)adenosine as a highly potent agonist for the adenosine A2 receptor</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>Several N6-(arylalkyl)adenosines related to N6-benzyladenosine were synthesized, and their A1 and A2 adenosine receptor binding affinities were determined. The annulated derivative N6-(1-naphthylmethyl)adenosine resulted in a very potent A2 agonist (A1 Ki = 24 nM, A2 Ki = 9.1 nM), whereas N6-(9-anthracenylmethyl)adenosine was virtually inactive (A1 Ki = 9,000 nM, A2 Ki = 29,000 nM). Interestingly, the structurally similar N6-(9-fluorenylmethyl)adenosine was the most potent A2 agonist reported to date, with a Ki of 4.9 nM in A2 binding and 5.1 nM in A1 binding. The homologues N6-9-fluorenyladenosine and N6-[2-(9-fluorenyl)ethyl]adenosine showed little or no activity at either adenosine receptor. Effects of these agents on heart rate and coronary flow in the isolated rat heart paralleled their A1 and A2 binding affinities, respectively. These data suggest that for high affinity at the A2 receptor a planar hydrophobic function at a certain distance and angle from the N6 nitrogen is required.</description><subject>Adenosine - analogs & derivatives</subject><subject>Adenosine - chemical synthesis</subject><subject>Adenosine - metabolism</subject><subject>Animals</subject><subject>Brain - metabolism</subject><subject>Carbohydrates. Nucleosides and nucleotides</subject><subject>Cell Membrane - metabolism</subject><subject>Chemistry</subject><subject>Coronary Circulation - drug effects</subject><subject>Exact sciences and technology</subject><subject>Fluorenes - chemical synthesis</subject><subject>Fluorenes - metabolism</subject><subject>Heart Rate - drug effects</subject><subject>In Vitro Techniques</subject><subject>Indicators and Reagents</subject><subject>Kinetics</subject><subject>Nucleosides, nucleotides and oligonucleotides</subject><subject>Organic chemistry</subject><subject>Preparations and properties</subject><subject>Rats</subject><subject>Receptors, Purinergic - metabolism</subject><subject>Structure-Activity Relationship</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1988</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpt0M9r2zAUB3AxNrqs22nngQ5j6xhu9cO2lGNo17RQ1kLDruJZlhulspVKMsz3_uFTSQg97CTB9_Mejy9Cnyk5pYTRs01PCJ_XQMryDZrRipGilKR8i2aEMFawmvH36EOMG5IdZfwIHXHOa8LEDD3_rouTRZgcuMfJ_YDWDD7awcRTfJ3_yXZWQ7J-wL7DL3ZedG70wQyT601av57BEDHgtX1YuwlvfcrjGB78YGPCnQ84rTM54AXDwWizTT58RO86cNF82r_HaHX5a3V-VdzcLq_PFzcFcFqlotFUcl3VwjSESMMqQTTRWpTzqmGkbSW0dStLmEPLKuikbpkoJdSdqGgjS36Mvu3WboN_Gk1MqrdRG-dgMH6MSkjCGa9phj93UAcfYzCd2gbbQ5gUJeqlcvWq8qy_7NeOTW_ag913nPOv-xyiBtcFGLSNB5ZPLCWTmRU7lusyfw8xhEdVCy4qtbq7V8srJpYXd3_Uffbfdx50VBs_hiFX998D_wEwuaUV</recordid><startdate>19880101</startdate><enddate>19880101</enddate><creator>Trivedi, B. K</creator><creator>Bristol, J. A</creator><creator>Bruns, R. F</creator><creator>Haleen, S. J</creator><creator>Steffen, R. P</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>19880101</creationdate><title>N6-(Arylalkyl)adenosines. Identification of N6-(9-fluorenylmethyl)adenosine as a highly potent agonist for the adenosine A2 receptor</title><author>Trivedi, B. K ; Bristol, J. A ; Bruns, R. F ; Haleen, S. J ; Steffen, R. P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a315t-bc183c567eb008e2570c0cc7495b20dd8ad6d84a9ad25af8cd2748a6f751b843</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1988</creationdate><topic>Adenosine - analogs & derivatives</topic><topic>Adenosine - chemical synthesis</topic><topic>Adenosine - metabolism</topic><topic>Animals</topic><topic>Brain - metabolism</topic><topic>Carbohydrates. Nucleosides and nucleotides</topic><topic>Cell Membrane - metabolism</topic><topic>Chemistry</topic><topic>Coronary Circulation - drug effects</topic><topic>Exact sciences and technology</topic><topic>Fluorenes - chemical synthesis</topic><topic>Fluorenes - metabolism</topic><topic>Heart Rate - drug effects</topic><topic>In Vitro Techniques</topic><topic>Indicators and Reagents</topic><topic>Kinetics</topic><topic>Nucleosides, nucleotides and oligonucleotides</topic><topic>Organic chemistry</topic><topic>Preparations and properties</topic><topic>Rats</topic><topic>Receptors, Purinergic - metabolism</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Trivedi, B. K</creatorcontrib><creatorcontrib>Bristol, J. A</creatorcontrib><creatorcontrib>Bruns, R. F</creatorcontrib><creatorcontrib>Haleen, S. J</creatorcontrib><creatorcontrib>Steffen, R. P</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>Trivedi, B. K</au><au>Bristol, J. A</au><au>Bruns, R. F</au><au>Haleen, S. J</au><au>Steffen, R. P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>N6-(Arylalkyl)adenosines. Identification of N6-(9-fluorenylmethyl)adenosine as a highly potent agonist for the adenosine A2 receptor</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>1988-01-01</date><risdate>1988</risdate><volume>31</volume><issue>1</issue><spage>271</spage><epage>273</epage><pages>271-273</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><abstract>Several N6-(arylalkyl)adenosines related to N6-benzyladenosine were synthesized, and their A1 and A2 adenosine receptor binding affinities were determined. The annulated derivative N6-(1-naphthylmethyl)adenosine resulted in a very potent A2 agonist (A1 Ki = 24 nM, A2 Ki = 9.1 nM), whereas N6-(9-anthracenylmethyl)adenosine was virtually inactive (A1 Ki = 9,000 nM, A2 Ki = 29,000 nM). Interestingly, the structurally similar N6-(9-fluorenylmethyl)adenosine was the most potent A2 agonist reported to date, with a Ki of 4.9 nM in A2 binding and 5.1 nM in A1 binding. The homologues N6-9-fluorenyladenosine and N6-[2-(9-fluorenyl)ethyl]adenosine showed little or no activity at either adenosine receptor. Effects of these agents on heart rate and coronary flow in the isolated rat heart paralleled their A1 and A2 binding affinities, respectively. These data suggest that for high affinity at the A2 receptor a planar hydrophobic function at a certain distance and angle from the N6 nitrogen is required.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>3336027</pmid><doi>10.1021/jm00396a044</doi><tpages>3</tpages></addata></record> |
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| ispartof | Journal of medicinal chemistry, 1988-01, Vol.31 (1), p.271-273 |
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| subjects | Adenosine - analogs & derivatives Adenosine - chemical synthesis Adenosine - metabolism Animals Brain - metabolism Carbohydrates. Nucleosides and nucleotides Cell Membrane - metabolism Chemistry Coronary Circulation - drug effects Exact sciences and technology Fluorenes - chemical synthesis Fluorenes - metabolism Heart Rate - drug effects In Vitro Techniques Indicators and Reagents Kinetics Nucleosides, nucleotides and oligonucleotides Organic chemistry Preparations and properties Rats Receptors, Purinergic - metabolism Structure-Activity Relationship |
| title | N6-(Arylalkyl)adenosines. Identification of N6-(9-fluorenylmethyl)adenosine as a highly potent agonist for the adenosine A2 receptor |
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