Asymmetric synthesis and biological evaluations of (+)- and (−)-6-dimethoxymethyl-1,4-dihydropyridine-3-carboxylic acid derivatives blocking N-type calcium channels
The novel asymmetric synthesis is reported for the preparation of optically pure (+)-4-(3-chlorophenyl)-6-dimethoxymethyl-2-methyl-1,4-dihydropyridine-3,5-dicarboxilic acid cinnamyl ester ((+)- 3) as a promising blocker for the N-type calcium channels. An efficient asymmetric synthesis of 1,4-dihydr...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2011-06, Vol.21 (11), p.3317-3319 |
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| creator | Yamamoto, Takashi Ohno, Seiji Niwa, Seiji Tokumasu, Munetaka Hagihara, Masako Koganei, Hajime Fujita, Shin-ichi Takeda, Tomoko Saitou, Yuki Iwayama, Satoshi Takahara, Akira Iwata, Seinosuke Shoji, Masataka |
| description | The novel asymmetric synthesis is reported for the preparation of optically pure (+)-4-(3-chlorophenyl)-6-dimethoxymethyl-2-methyl-1,4-dihydropyridine-3,5-dicarboxilic acid cinnamyl ester ((+)-
3) as a promising blocker for the N-type calcium channels.
An efficient asymmetric synthesis of 1,4-dihydropyridine derivatives is described. The key step is the stereoselective Michael addition using
t-butyl ester of
l-valine as a chiral auxiliary to achieve good ee (>95% for all the tested experiments) and moderate yield. With this method, (+)-4-(3-chlorophenyl)-6-dimethoxymethyl-2-methyl-1,4-dihydropyridine-3,5-dicarboxylic acid cinnamyl ester was obtained and was characterized as a promising N-type calcium channel blocker with improved selectivity over L-type compared to its (−)- and racemic isomers. |
| doi_str_mv | 10.1016/j.bmcl.2011.04.007 |
| format | Article |
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3) as a promising blocker for the N-type calcium channels.
An efficient asymmetric synthesis of 1,4-dihydropyridine derivatives is described. The key step is the stereoselective Michael addition using
t-butyl ester of
l-valine as a chiral auxiliary to achieve good ee (>95% for all the tested experiments) and moderate yield. With this method, (+)-4-(3-chlorophenyl)-6-dimethoxymethyl-2-methyl-1,4-dihydropyridine-3,5-dicarboxylic acid cinnamyl ester was obtained and was characterized as a promising N-type calcium channel blocker with improved selectivity over L-type compared to its (−)- and racemic isomers.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2011.04.007</identifier><identifier>PMID: 21514827</identifier><language>eng</language><publisher>Amsterdam: Elsevier Ltd</publisher><subject>1,4-Dihydropyridine derivative ; Animals ; Asymmetric synthesis ; Biological and medical sciences ; calcium channel blockers ; calcium channels ; Calcium Channels, N-Type - drug effects ; Carboxylic Acids - chemical synthesis ; Carboxylic Acids - chemistry ; Carboxylic Acids - pharmacology ; Cell Line, Tumor ; Dihydropyridines - chemical synthesis ; Dihydropyridines - chemistry ; Dihydropyridines - pharmacology ; Humans ; isomers ; Medical sciences ; Methyl Ethers - chemical synthesis ; Methyl Ethers - chemistry ; Methyl Ethers - pharmacology ; Miscellaneous ; Molecular Structure ; N-type calcium channel blocker ; Neuropharmacology ; Pharmacology. Drug treatments ; Protein Binding - drug effects ; Rats ; Stereoisomerism ; Structure-Activity Relationship ; Structure–activity relationships</subject><ispartof>Bioorganic & medicinal chemistry letters, 2011-06, Vol.21 (11), p.3317-3319</ispartof><rights>2011 Elsevier Ltd</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c532t-4d790872cd7d6b57d83252a306afa7d0dc88ece1585b1bd96b7193242934c7d83</citedby><cites>FETCH-LOGICAL-c532t-4d790872cd7d6b57d83252a306afa7d0dc88ece1585b1bd96b7193242934c7d83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0960894X11004549$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24231617$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21514827$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yamamoto, Takashi</creatorcontrib><creatorcontrib>Ohno, Seiji</creatorcontrib><creatorcontrib>Niwa, Seiji</creatorcontrib><creatorcontrib>Tokumasu, Munetaka</creatorcontrib><creatorcontrib>Hagihara, Masako</creatorcontrib><creatorcontrib>Koganei, Hajime</creatorcontrib><creatorcontrib>Fujita, Shin-ichi</creatorcontrib><creatorcontrib>Takeda, Tomoko</creatorcontrib><creatorcontrib>Saitou, Yuki</creatorcontrib><creatorcontrib>Iwayama, Satoshi</creatorcontrib><creatorcontrib>Takahara, Akira</creatorcontrib><creatorcontrib>Iwata, Seinosuke</creatorcontrib><creatorcontrib>Shoji, Masataka</creatorcontrib><title>Asymmetric synthesis and biological evaluations of (+)- and (−)-6-dimethoxymethyl-1,4-dihydropyridine-3-carboxylic acid derivatives blocking N-type calcium channels</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>The novel asymmetric synthesis is reported for the preparation of optically pure (+)-4-(3-chlorophenyl)-6-dimethoxymethyl-2-methyl-1,4-dihydropyridine-3,5-dicarboxilic acid cinnamyl ester ((+)-
3) as a promising blocker for the N-type calcium channels.
An efficient asymmetric synthesis of 1,4-dihydropyridine derivatives is described. The key step is the stereoselective Michael addition using
t-butyl ester of
l-valine as a chiral auxiliary to achieve good ee (>95% for all the tested experiments) and moderate yield. With this method, (+)-4-(3-chlorophenyl)-6-dimethoxymethyl-2-methyl-1,4-dihydropyridine-3,5-dicarboxylic acid cinnamyl ester was obtained and was characterized as a promising N-type calcium channel blocker with improved selectivity over L-type compared to its (−)- and racemic isomers.</description><subject>1,4-Dihydropyridine derivative</subject><subject>Animals</subject><subject>Asymmetric synthesis</subject><subject>Biological and medical sciences</subject><subject>calcium channel blockers</subject><subject>calcium channels</subject><subject>Calcium Channels, N-Type - drug effects</subject><subject>Carboxylic Acids - chemical synthesis</subject><subject>Carboxylic Acids - chemistry</subject><subject>Carboxylic Acids - pharmacology</subject><subject>Cell Line, Tumor</subject><subject>Dihydropyridines - chemical synthesis</subject><subject>Dihydropyridines - chemistry</subject><subject>Dihydropyridines - pharmacology</subject><subject>Humans</subject><subject>isomers</subject><subject>Medical sciences</subject><subject>Methyl Ethers - chemical synthesis</subject><subject>Methyl Ethers - chemistry</subject><subject>Methyl Ethers - pharmacology</subject><subject>Miscellaneous</subject><subject>Molecular Structure</subject><subject>N-type calcium channel blocker</subject><subject>Neuropharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Protein Binding - drug effects</subject><subject>Rats</subject><subject>Stereoisomerism</subject><subject>Structure-Activity Relationship</subject><subject>Structure–activity relationships</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFks9u1DAQxiMEokvhBTiAL4hW4MV2nMSRuFQV_6QKDlCJm-XYk10vTry1k1XzBj3zEDwYT4LTXeAGp5Gs33zfzHzOsseULCmh5avNsum0WzJC6ZLwJSHVnWxBeclxzklxN1uQuiRY1PzrUfYgxg0hlBPO72dHjBaUC1Ytsh9nceo6GILVKE79sIZoI1K9QY31zq-sVg7BTrlRDdb3EfkWnbw4xbfIyc-b76e4xMYmhbW_nuYyOUxf8vS2nkzw2ylYY3vAOdYqNIlxyUlpa5CBYHdJdQcRNc7rb7ZfoY94mLaAkqu2Y4f0WvU9uPgwu9cqF-HRoR5nl2_ffDl_jy8-vftwfnaBdZGzAXNT1URUTJvKlE1RGZGzgqmclKpVlSFGCwEaaCGKhjamLpuK1jnjrM65nunj7Pledxv81QhxkJ2NGpxTPfgxyqRNc0E5-z9ZCsLKSsyabE_q4GMM0MptsJ0Kk6REzkHKjZyDlHOQknCZgkxNTw7yY9OB-dPyO7kEPDsAKqZrtUH12sa_XBqRlnTmnu65VnmpViExl5-TU5F-Q87F7Sav90S6M-wsBBm1hV6DsQH0II23_5r0F7bJx1I</recordid><startdate>20110601</startdate><enddate>20110601</enddate><creator>Yamamoto, Takashi</creator><creator>Ohno, Seiji</creator><creator>Niwa, Seiji</creator><creator>Tokumasu, Munetaka</creator><creator>Hagihara, Masako</creator><creator>Koganei, Hajime</creator><creator>Fujita, Shin-ichi</creator><creator>Takeda, Tomoko</creator><creator>Saitou, Yuki</creator><creator>Iwayama, Satoshi</creator><creator>Takahara, Akira</creator><creator>Iwata, Seinosuke</creator><creator>Shoji, Masataka</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>FBQ</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><scope>7QO</scope><scope>7QP</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20110601</creationdate><title>Asymmetric synthesis and biological evaluations of (+)- and (−)-6-dimethoxymethyl-1,4-dihydropyridine-3-carboxylic acid derivatives blocking N-type calcium channels</title><author>Yamamoto, Takashi ; Ohno, Seiji ; Niwa, Seiji ; Tokumasu, Munetaka ; Hagihara, Masako ; Koganei, Hajime ; Fujita, Shin-ichi ; Takeda, Tomoko ; Saitou, Yuki ; Iwayama, Satoshi ; Takahara, Akira ; Iwata, Seinosuke ; Shoji, Masataka</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c532t-4d790872cd7d6b57d83252a306afa7d0dc88ece1585b1bd96b7193242934c7d83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>1,4-Dihydropyridine derivative</topic><topic>Animals</topic><topic>Asymmetric synthesis</topic><topic>Biological and medical sciences</topic><topic>calcium channel blockers</topic><topic>calcium channels</topic><topic>Calcium Channels, N-Type - drug effects</topic><topic>Carboxylic Acids - chemical synthesis</topic><topic>Carboxylic Acids - chemistry</topic><topic>Carboxylic Acids - pharmacology</topic><topic>Cell Line, Tumor</topic><topic>Dihydropyridines - chemical synthesis</topic><topic>Dihydropyridines - chemistry</topic><topic>Dihydropyridines - pharmacology</topic><topic>Humans</topic><topic>isomers</topic><topic>Medical sciences</topic><topic>Methyl Ethers - chemical synthesis</topic><topic>Methyl Ethers - chemistry</topic><topic>Methyl Ethers - pharmacology</topic><topic>Miscellaneous</topic><topic>Molecular Structure</topic><topic>N-type calcium channel blocker</topic><topic>Neuropharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Protein Binding - drug effects</topic><topic>Rats</topic><topic>Stereoisomerism</topic><topic>Structure-Activity Relationship</topic><topic>Structure–activity relationships</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yamamoto, Takashi</creatorcontrib><creatorcontrib>Ohno, Seiji</creatorcontrib><creatorcontrib>Niwa, Seiji</creatorcontrib><creatorcontrib>Tokumasu, Munetaka</creatorcontrib><creatorcontrib>Hagihara, Masako</creatorcontrib><creatorcontrib>Koganei, Hajime</creatorcontrib><creatorcontrib>Fujita, Shin-ichi</creatorcontrib><creatorcontrib>Takeda, Tomoko</creatorcontrib><creatorcontrib>Saitou, Yuki</creatorcontrib><creatorcontrib>Iwayama, Satoshi</creatorcontrib><creatorcontrib>Takahara, Akira</creatorcontrib><creatorcontrib>Iwata, Seinosuke</creatorcontrib><creatorcontrib>Shoji, Masataka</creatorcontrib><collection>AGRIS</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><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue 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>Yamamoto, Takashi</au><au>Ohno, Seiji</au><au>Niwa, Seiji</au><au>Tokumasu, Munetaka</au><au>Hagihara, Masako</au><au>Koganei, Hajime</au><au>Fujita, Shin-ichi</au><au>Takeda, Tomoko</au><au>Saitou, Yuki</au><au>Iwayama, Satoshi</au><au>Takahara, Akira</au><au>Iwata, Seinosuke</au><au>Shoji, Masataka</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Asymmetric synthesis and biological evaluations of (+)- and (−)-6-dimethoxymethyl-1,4-dihydropyridine-3-carboxylic acid derivatives blocking N-type calcium channels</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2011-06-01</date><risdate>2011</risdate><volume>21</volume><issue>11</issue><spage>3317</spage><epage>3319</epage><pages>3317-3319</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>The novel asymmetric synthesis is reported for the preparation of optically pure (+)-4-(3-chlorophenyl)-6-dimethoxymethyl-2-methyl-1,4-dihydropyridine-3,5-dicarboxilic acid cinnamyl ester ((+)-
3) as a promising blocker for the N-type calcium channels.
An efficient asymmetric synthesis of 1,4-dihydropyridine derivatives is described. The key step is the stereoselective Michael addition using
t-butyl ester of
l-valine as a chiral auxiliary to achieve good ee (>95% for all the tested experiments) and moderate yield. With this method, (+)-4-(3-chlorophenyl)-6-dimethoxymethyl-2-methyl-1,4-dihydropyridine-3,5-dicarboxylic acid cinnamyl ester was obtained and was characterized as a promising N-type calcium channel blocker with improved selectivity over L-type compared to its (−)- and racemic isomers.</abstract><cop>Amsterdam</cop><pub>Elsevier Ltd</pub><pmid>21514827</pmid><doi>10.1016/j.bmcl.2011.04.007</doi><tpages>3</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2011-06, Vol.21 (11), p.3317-3319 |
| issn | 0960-894X 1464-3405 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_872138142 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | 1,4-Dihydropyridine derivative Animals Asymmetric synthesis Biological and medical sciences calcium channel blockers calcium channels Calcium Channels, N-Type - drug effects Carboxylic Acids - chemical synthesis Carboxylic Acids - chemistry Carboxylic Acids - pharmacology Cell Line, Tumor Dihydropyridines - chemical synthesis Dihydropyridines - chemistry Dihydropyridines - pharmacology Humans isomers Medical sciences Methyl Ethers - chemical synthesis Methyl Ethers - chemistry Methyl Ethers - pharmacology Miscellaneous Molecular Structure N-type calcium channel blocker Neuropharmacology Pharmacology. Drug treatments Protein Binding - drug effects Rats Stereoisomerism Structure-Activity Relationship Structure–activity relationships |
| title | Asymmetric synthesis and biological evaluations of (+)- and (−)-6-dimethoxymethyl-1,4-dihydropyridine-3-carboxylic acid derivatives blocking N-type calcium channels |
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