Synthesis of 2-Chloro-N6-Substituted-4′-thioadenosine-5′-N, N-dialkyluronamides as Potent and Selective A3 Adenosine Receptor Antagonists
Abstract The highly selective A3 receptor agonist, 4′-thio-Cl-IB-MECA was successfully converted into selective A3 receptor antagonists by appending a second N-alkyl group on the 5′-uronamide position. This result indicates that the hydrogen bonding ability of the 5′-uronamide is essential for the c...
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| Veröffentlicht in: | Nucleic Acids Symposium Series 2008, Vol.52 (1), p.645-646 |
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| container_title | Nucleic Acids Symposium Series |
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| creator | Choi, Won Jun Lee, Hyuk Woo Hou, Xiyan Kim, Hea OK Jacobson, Kenneth A. Jeong, Lak Shin |
| description | Abstract
The highly selective A3 receptor agonist, 4′-thio-Cl-IB-MECA was successfully converted into selective A3 receptor antagonists by appending a second N-alkyl group on the 5′-uronamide position. This result indicates that the hydrogen bonding ability of the 5′-uronamide is essential for the conformational change required for the receptor activation. Among compounds tested, a N6-(3-bromobenzyl) derivative with 5′-dimethyluronamide exhibited the highest binding affinity (Ki = 9.32 nM) at the human A3 AR with very low binding affinities to other AR subtypes. |
| doi_str_mv | 10.1093/nass/nrn326 |
| format | Article |
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The highly selective A3 receptor agonist, 4′-thio-Cl-IB-MECA was successfully converted into selective A3 receptor antagonists by appending a second N-alkyl group on the 5′-uronamide position. This result indicates that the hydrogen bonding ability of the 5′-uronamide is essential for the conformational change required for the receptor activation. Among compounds tested, a N6-(3-bromobenzyl) derivative with 5′-dimethyluronamide exhibited the highest binding affinity (Ki = 9.32 nM) at the human A3 AR with very low binding affinities to other AR subtypes.</description><identifier>ISSN: 0261-3166</identifier><identifier>EISSN: 1746-8272</identifier><identifier>DOI: 10.1093/nass/nrn326</identifier><identifier>PMID: 18776545</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Adenosine - analogs & derivatives ; Adenosine - chemistry ; Adenosine A3 Receptor Antagonists ; Animals ; CHO Cells ; Cricetinae ; Cricetulus ; Humans ; Hydrogen Bonding ; Purine Nucleosides - chemical synthesis ; Purine Nucleosides - metabolism ; Receptor, Adenosine A3 - metabolism</subject><ispartof>Nucleic Acids Symposium Series, 2008, Vol.52 (1), p.645-646</ispartof><rights>2008 Oxford University Press 2008</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3266-8a99d77c8b0f0059175555cc3a9d2eb16abc52a620e117bd0da1eeed3a0c46cd3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,883,1601,4012,27910,27911,27912</link.rule.ids><linktorsrc>$$Uhttps://dx.doi.org/10.1093/nass/nrn326$$EView_record_in_Oxford_University_Press$$FView_record_in_$$GOxford_University_Press</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18776545$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Choi, Won Jun</creatorcontrib><creatorcontrib>Lee, Hyuk Woo</creatorcontrib><creatorcontrib>Hou, Xiyan</creatorcontrib><creatorcontrib>Kim, Hea OK</creatorcontrib><creatorcontrib>Jacobson, Kenneth A.</creatorcontrib><creatorcontrib>Jeong, Lak Shin</creatorcontrib><title>Synthesis of 2-Chloro-N6-Substituted-4′-thioadenosine-5′-N, N-dialkyluronamides as Potent and Selective A3 Adenosine Receptor Antagonists</title><title>Nucleic Acids Symposium Series</title><addtitle>Nucleic Acids Symp Ser (Oxf)</addtitle><description>Abstract
The highly selective A3 receptor agonist, 4′-thio-Cl-IB-MECA was successfully converted into selective A3 receptor antagonists by appending a second N-alkyl group on the 5′-uronamide position. This result indicates that the hydrogen bonding ability of the 5′-uronamide is essential for the conformational change required for the receptor activation. Among compounds tested, a N6-(3-bromobenzyl) derivative with 5′-dimethyluronamide exhibited the highest binding affinity (Ki = 9.32 nM) at the human A3 AR with very low binding affinities to other AR subtypes.</description><subject>Adenosine - analogs & derivatives</subject><subject>Adenosine - chemistry</subject><subject>Adenosine A3 Receptor Antagonists</subject><subject>Animals</subject><subject>CHO Cells</subject><subject>Cricetinae</subject><subject>Cricetulus</subject><subject>Humans</subject><subject>Hydrogen Bonding</subject><subject>Purine Nucleosides - chemical synthesis</subject><subject>Purine Nucleosides - metabolism</subject><subject>Receptor, Adenosine A3 - metabolism</subject><issn>0261-3166</issn><issn>1746-8272</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc9uEzEQhy1ERaPSE3fkExzA1H927ewFKYqAVqoCInC2vPakMWzs1PZWyo0X4GV4JJ4ERwkFLszF0vjTNzP6IfSE0VeMduIimJwvQgqCywdowlQjyZQr_hBNKJeMCCblKTrP-Qut1VCqOvUInbKpUrJt2gn6vtyFsobsM44rzMl8PcQUyUKS5djn4stYwJHm57cfpKx9NA5CzD4AafetxUu8IM6b4etuGFMMZuMdZGwy_hALhIJNcHgJA9ji7wDPBJ79FuCPYGFbYsKzUMxNDD6X_BidrMyQ4fz4nqHPb998ml-S6_fvruaza2LrnfVC03VOKTvt6YrStmOqrWWtMJ3j0DNpettyIzkFxlTvqDMMAJww1DbSOnGGXh-827HfgLN11WQGvU1-Y9JOR-P1vz_Br_VNvNNcNVMuRRU8PwpSvB0hF73x2cIwmABxzFoJoRqmKK3kiwNpU8w5wep-CqN6H6HeR6gPEVb66d-L_WGPgVXg2QGI4_a_pl93Eaql</recordid><startdate>2008</startdate><enddate>2008</enddate><creator>Choi, Won Jun</creator><creator>Lee, Hyuk Woo</creator><creator>Hou, Xiyan</creator><creator>Kim, Hea OK</creator><creator>Jacobson, Kenneth A.</creator><creator>Jeong, Lak Shin</creator><general>Oxford University Press</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>5PM</scope></search><sort><creationdate>2008</creationdate><title>Synthesis of 2-Chloro-N6-Substituted-4′-thioadenosine-5′-N, N-dialkyluronamides as Potent and Selective A3 Adenosine Receptor Antagonists</title><author>Choi, Won Jun ; Lee, Hyuk Woo ; Hou, Xiyan ; Kim, Hea OK ; Jacobson, Kenneth A. ; Jeong, Lak Shin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3266-8a99d77c8b0f0059175555cc3a9d2eb16abc52a620e117bd0da1eeed3a0c46cd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adenosine - analogs & derivatives</topic><topic>Adenosine - chemistry</topic><topic>Adenosine A3 Receptor Antagonists</topic><topic>Animals</topic><topic>CHO Cells</topic><topic>Cricetinae</topic><topic>Cricetulus</topic><topic>Humans</topic><topic>Hydrogen Bonding</topic><topic>Purine Nucleosides - chemical synthesis</topic><topic>Purine Nucleosides - metabolism</topic><topic>Receptor, Adenosine A3 - metabolism</topic><toplevel>online_resources</toplevel><creatorcontrib>Choi, Won Jun</creatorcontrib><creatorcontrib>Lee, Hyuk Woo</creatorcontrib><creatorcontrib>Hou, Xiyan</creatorcontrib><creatorcontrib>Kim, Hea OK</creatorcontrib><creatorcontrib>Jacobson, Kenneth A.</creatorcontrib><creatorcontrib>Jeong, Lak Shin</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>PubMed Central (Full Participant titles)</collection><jtitle>Nucleic Acids Symposium Series</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Choi, Won Jun</au><au>Lee, Hyuk Woo</au><au>Hou, Xiyan</au><au>Kim, Hea OK</au><au>Jacobson, Kenneth A.</au><au>Jeong, Lak Shin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis of 2-Chloro-N6-Substituted-4′-thioadenosine-5′-N, N-dialkyluronamides as Potent and Selective A3 Adenosine Receptor Antagonists</atitle><jtitle>Nucleic Acids Symposium Series</jtitle><addtitle>Nucleic Acids Symp Ser (Oxf)</addtitle><date>2008</date><risdate>2008</risdate><volume>52</volume><issue>1</issue><spage>645</spage><epage>646</epage><pages>645-646</pages><issn>0261-3166</issn><eissn>1746-8272</eissn><abstract>Abstract
The highly selective A3 receptor agonist, 4′-thio-Cl-IB-MECA was successfully converted into selective A3 receptor antagonists by appending a second N-alkyl group on the 5′-uronamide position. This result indicates that the hydrogen bonding ability of the 5′-uronamide is essential for the conformational change required for the receptor activation. Among compounds tested, a N6-(3-bromobenzyl) derivative with 5′-dimethyluronamide exhibited the highest binding affinity (Ki = 9.32 nM) at the human A3 AR with very low binding affinities to other AR subtypes.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>18776545</pmid><doi>10.1093/nass/nrn326</doi><tpages>2</tpages><oa>free_for_read</oa></addata></record> |
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| issn | 0261-3166 1746-8272 |
| language | eng |
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| source | Oxford Journals Open Access Collection |
| subjects | Adenosine - analogs & derivatives Adenosine - chemistry Adenosine A3 Receptor Antagonists Animals CHO Cells Cricetinae Cricetulus Humans Hydrogen Bonding Purine Nucleosides - chemical synthesis Purine Nucleosides - metabolism Receptor, Adenosine A3 - metabolism |
| title | Synthesis of 2-Chloro-N6-Substituted-4′-thioadenosine-5′-N, N-dialkyluronamides as Potent and Selective A3 Adenosine Receptor Antagonists |
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