Synthesis of polyhydroxy piperidines and their analogues: a novel approach towards selective inhibitors of alpha-glucosidase
Various polyhydroxy piperidine azasugars have been synthesized from precursors 18a and 18b, obtained in both enantiomeric forms from d-ribose. Out of these polyhydroxy piperidine azasugars, 22, 39 and 20 were found to be potent as well as selective inhibitors of alpha-glucosidase with K(i) values ra...
Gespeichert in:
| Veröffentlicht in: | Organic & biomolecular chemistry 2008-01, Vol.6 (14), p.2587-2595 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2595 |
|---|---|
| container_issue | 14 |
| container_start_page | 2587 |
| container_title | Organic & biomolecular chemistry |
| container_volume | 6 |
| creator | Pandey, Ganesh Bharadwaj, Kishor Chandra Khan, M Islam Shashidhara, K S Puranik, Vedavati G |
| description | Various polyhydroxy piperidine azasugars have been synthesized from precursors 18a and 18b, obtained in both enantiomeric forms from d-ribose. Out of these polyhydroxy piperidine azasugars, 22, 39 and 20 were found to be potent as well as selective inhibitors of alpha-glucosidase with K(i) values ranging as low as 1.07 microM, 16.4 microM, and 88.2 microM, respectively. Replacement of the hydroxy methylene moiety of (K(i) 33% at 1 mM) by an amino methylene moiety (32, K(i) 36.8 microM) showed a remarkable increase in the activity (almost 30 times). Furthermore, increasing the lipophilicity of by N-alkylation with a dodecyl group (36) showed a three-fold enhancement in the activity (K(i) 217 microM to K(i) 72.3 microM). |
| doi_str_mv | 10.1039/b804278k |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_69292235</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>69292235</sourcerecordid><originalsourceid>FETCH-LOGICAL-c281t-e1a8b03f78de1e93423504496ee55590ab5dfae5439714549be46a91f005a49c3</originalsourceid><addsrcrecordid>eNpFkE1LxDAURYMozjgK_gLJStxUkzZpG3cy-AUDLtR1eW1fp9FMU5N2tOCPtzqjru5dHA6XS8gxZ-ecReoiT5kIk_R1h0y5SJKAyUjt_vWQTciB9y-McZXEYp9MeBozFqZsSj4fh6ar0WtPbUVba4Z6KJ39GGirW3S61A16Ck1JR0q7sYGxyx79JQXa2DUaCm3rLBQ17ew7uNJTjwaLTq-R6qbWue6s-7GDaWsIlqYvrNcleDwkexUYj0fbnJHnm-un-V2weLi9n18tgiJMeRcghzRnUZWkJXJUkQgjyYRQMaKUUjHIZVkBShGphAspVI4iBsUrxiQIVUQzcrrxjkPfxu1dttK-QGOgQdv7LFahCkfpCJ5twMJZ7x1WWev0CtyQcZZ9P539Pj2iJ1tnn6-w_Ae310ZfbcB7RA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>69292235</pqid></control><display><type>article</type><title>Synthesis of polyhydroxy piperidines and their analogues: a novel approach towards selective inhibitors of alpha-glucosidase</title><source>MEDLINE</source><source>Royal Society Of Chemistry Journals 2008-</source><source>Alma/SFX Local Collection</source><creator>Pandey, Ganesh ; Bharadwaj, Kishor Chandra ; Khan, M Islam ; Shashidhara, K S ; Puranik, Vedavati G</creator><creatorcontrib>Pandey, Ganesh ; Bharadwaj, Kishor Chandra ; Khan, M Islam ; Shashidhara, K S ; Puranik, Vedavati G</creatorcontrib><description>Various polyhydroxy piperidine azasugars have been synthesized from precursors 18a and 18b, obtained in both enantiomeric forms from d-ribose. Out of these polyhydroxy piperidine azasugars, 22, 39 and 20 were found to be potent as well as selective inhibitors of alpha-glucosidase with K(i) values ranging as low as 1.07 microM, 16.4 microM, and 88.2 microM, respectively. Replacement of the hydroxy methylene moiety of (K(i) 33% at 1 mM) by an amino methylene moiety (32, K(i) 36.8 microM) showed a remarkable increase in the activity (almost 30 times). Furthermore, increasing the lipophilicity of by N-alkylation with a dodecyl group (36) showed a three-fold enhancement in the activity (K(i) 217 microM to K(i) 72.3 microM).</description><identifier>ISSN: 1477-0520</identifier><identifier>EISSN: 1477-0539</identifier><identifier>DOI: 10.1039/b804278k</identifier><identifier>PMID: 18600280</identifier><language>eng</language><publisher>England</publisher><subject>Aspergillus - drug effects ; Aspergillus - enzymology ; Enzyme Inhibitors - chemical synthesis ; Enzyme Inhibitors - chemistry ; Enzyme Inhibitors - pharmacology ; Glycoside Hydrolase Inhibitors ; Piperidines - chemical synthesis ; Piperidines - chemistry ; Piperidines - pharmacology ; Substrate Specificity</subject><ispartof>Organic & biomolecular chemistry, 2008-01, Vol.6 (14), p.2587-2595</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c281t-e1a8b03f78de1e93423504496ee55590ab5dfae5439714549be46a91f005a49c3</citedby><cites>FETCH-LOGICAL-c281t-e1a8b03f78de1e93423504496ee55590ab5dfae5439714549be46a91f005a49c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18600280$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pandey, Ganesh</creatorcontrib><creatorcontrib>Bharadwaj, Kishor Chandra</creatorcontrib><creatorcontrib>Khan, M Islam</creatorcontrib><creatorcontrib>Shashidhara, K S</creatorcontrib><creatorcontrib>Puranik, Vedavati G</creatorcontrib><title>Synthesis of polyhydroxy piperidines and their analogues: a novel approach towards selective inhibitors of alpha-glucosidase</title><title>Organic & biomolecular chemistry</title><addtitle>Org Biomol Chem</addtitle><description>Various polyhydroxy piperidine azasugars have been synthesized from precursors 18a and 18b, obtained in both enantiomeric forms from d-ribose. Out of these polyhydroxy piperidine azasugars, 22, 39 and 20 were found to be potent as well as selective inhibitors of alpha-glucosidase with K(i) values ranging as low as 1.07 microM, 16.4 microM, and 88.2 microM, respectively. Replacement of the hydroxy methylene moiety of (K(i) 33% at 1 mM) by an amino methylene moiety (32, K(i) 36.8 microM) showed a remarkable increase in the activity (almost 30 times). Furthermore, increasing the lipophilicity of by N-alkylation with a dodecyl group (36) showed a three-fold enhancement in the activity (K(i) 217 microM to K(i) 72.3 microM).</description><subject>Aspergillus - drug effects</subject><subject>Aspergillus - enzymology</subject><subject>Enzyme Inhibitors - chemical synthesis</subject><subject>Enzyme Inhibitors - chemistry</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Glycoside Hydrolase Inhibitors</subject><subject>Piperidines - chemical synthesis</subject><subject>Piperidines - chemistry</subject><subject>Piperidines - pharmacology</subject><subject>Substrate Specificity</subject><issn>1477-0520</issn><issn>1477-0539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkE1LxDAURYMozjgK_gLJStxUkzZpG3cy-AUDLtR1eW1fp9FMU5N2tOCPtzqjru5dHA6XS8gxZ-ecReoiT5kIk_R1h0y5SJKAyUjt_vWQTciB9y-McZXEYp9MeBozFqZsSj4fh6ar0WtPbUVba4Z6KJ39GGirW3S61A16Ck1JR0q7sYGxyx79JQXa2DUaCm3rLBQ17ew7uNJTjwaLTq-R6qbWue6s-7GDaWsIlqYvrNcleDwkexUYj0fbnJHnm-un-V2weLi9n18tgiJMeRcghzRnUZWkJXJUkQgjyYRQMaKUUjHIZVkBShGphAspVI4iBsUrxiQIVUQzcrrxjkPfxu1dttK-QGOgQdv7LFahCkfpCJ5twMJZ7x1WWev0CtyQcZZ9P539Pj2iJ1tnn6-w_Ae310ZfbcB7RA</recordid><startdate>20080101</startdate><enddate>20080101</enddate><creator>Pandey, Ganesh</creator><creator>Bharadwaj, Kishor Chandra</creator><creator>Khan, M Islam</creator><creator>Shashidhara, K S</creator><creator>Puranik, Vedavati G</creator><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>20080101</creationdate><title>Synthesis of polyhydroxy piperidines and their analogues: a novel approach towards selective inhibitors of alpha-glucosidase</title><author>Pandey, Ganesh ; Bharadwaj, Kishor Chandra ; Khan, M Islam ; Shashidhara, K S ; Puranik, Vedavati G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c281t-e1a8b03f78de1e93423504496ee55590ab5dfae5439714549be46a91f005a49c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Aspergillus - drug effects</topic><topic>Aspergillus - enzymology</topic><topic>Enzyme Inhibitors - chemical synthesis</topic><topic>Enzyme Inhibitors - chemistry</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Glycoside Hydrolase Inhibitors</topic><topic>Piperidines - chemical synthesis</topic><topic>Piperidines - chemistry</topic><topic>Piperidines - pharmacology</topic><topic>Substrate Specificity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pandey, Ganesh</creatorcontrib><creatorcontrib>Bharadwaj, Kishor Chandra</creatorcontrib><creatorcontrib>Khan, M Islam</creatorcontrib><creatorcontrib>Shashidhara, K S</creatorcontrib><creatorcontrib>Puranik, Vedavati G</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><jtitle>Organic & biomolecular chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pandey, Ganesh</au><au>Bharadwaj, Kishor Chandra</au><au>Khan, M Islam</au><au>Shashidhara, K S</au><au>Puranik, Vedavati G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis of polyhydroxy piperidines and their analogues: a novel approach towards selective inhibitors of alpha-glucosidase</atitle><jtitle>Organic & biomolecular chemistry</jtitle><addtitle>Org Biomol Chem</addtitle><date>2008-01-01</date><risdate>2008</risdate><volume>6</volume><issue>14</issue><spage>2587</spage><epage>2595</epage><pages>2587-2595</pages><issn>1477-0520</issn><eissn>1477-0539</eissn><abstract>Various polyhydroxy piperidine azasugars have been synthesized from precursors 18a and 18b, obtained in both enantiomeric forms from d-ribose. Out of these polyhydroxy piperidine azasugars, 22, 39 and 20 were found to be potent as well as selective inhibitors of alpha-glucosidase with K(i) values ranging as low as 1.07 microM, 16.4 microM, and 88.2 microM, respectively. Replacement of the hydroxy methylene moiety of (K(i) 33% at 1 mM) by an amino methylene moiety (32, K(i) 36.8 microM) showed a remarkable increase in the activity (almost 30 times). Furthermore, increasing the lipophilicity of by N-alkylation with a dodecyl group (36) showed a three-fold enhancement in the activity (K(i) 217 microM to K(i) 72.3 microM).</abstract><cop>England</cop><pmid>18600280</pmid><doi>10.1039/b804278k</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1477-0520 |
| ispartof | Organic & biomolecular chemistry, 2008-01, Vol.6 (14), p.2587-2595 |
| issn | 1477-0520 1477-0539 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_69292235 |
| source | MEDLINE; Royal Society Of Chemistry Journals 2008-; Alma/SFX Local Collection |
| subjects | Aspergillus - drug effects Aspergillus - enzymology Enzyme Inhibitors - chemical synthesis Enzyme Inhibitors - chemistry Enzyme Inhibitors - pharmacology Glycoside Hydrolase Inhibitors Piperidines - chemical synthesis Piperidines - chemistry Piperidines - pharmacology Substrate Specificity |
| title | Synthesis of polyhydroxy piperidines and their analogues: a novel approach towards selective inhibitors of alpha-glucosidase |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-05T05%3A56%3A56IST&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=Synthesis%20of%20polyhydroxy%20piperidines%20and%20their%20analogues:%20a%20novel%20approach%20towards%20selective%20inhibitors%20of%20alpha-glucosidase&rft.jtitle=Organic%20&%20biomolecular%20chemistry&rft.au=Pandey,%20Ganesh&rft.date=2008-01-01&rft.volume=6&rft.issue=14&rft.spage=2587&rft.epage=2595&rft.pages=2587-2595&rft.issn=1477-0520&rft.eissn=1477-0539&rft_id=info:doi/10.1039/b804278k&rft_dat=%3Cproquest_cross%3E69292235%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=69292235&rft_id=info:pmid/18600280&rfr_iscdi=true |