Imidazolines as efficacious glucose-dependent stimulators of insulin secretion
Synthesis of a series of imidazolines with glucose dependent effects on insulin exocytosis from pancreatic β-cells is reported. Regioisomers and enantiomers were found to exhibit marked differences in exocytotic effects as well as different activities on the K ATP-channel; the ( R (+)) isomer of 2-[...
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| Veröffentlicht in: | European journal of medicinal chemistry 2003-04, Vol.38 (4), p.357-362 |
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| container_title | European journal of medicinal chemistry |
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| creator | Jakobsen, Palle Madsen, Peter Andersen, HenrikSune |
| description | Synthesis of a series of imidazolines with glucose dependent effects on insulin exocytosis from pancreatic β-cells is reported. Regioisomers and enantiomers were found to exhibit marked differences in exocytotic effects as well as different activities on the K
ATP-channel; the (
R (+)) isomer of 2-[2-(4,5-dihydro-1
H-imidazol-2-yl)-1-thiophene-2-ylethyl]pyridine (
4a) and the (+) isomer of 2-[2-(4,5-dihydro-1
H-imidazol-2-yl)-1-thiophene-3-ylethyl]pyridine (
4d) were found to give a significant increase in insulin release—in contrast to findings for their enantiomers—without influence on the K
ATP-channel. The (+) isomer (
4a) showed glucose dependent insulin release from β-cells at concentrations above 2.5 mM and a marked glucose lowering effect in
ob/
ob mice as well as in fed but not in fasted rats. |
| doi_str_mv | 10.1016/S0223-5234(03)00041-2 |
| format | Article |
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ATP-channel; the (
R (+)) isomer of 2-[2-(4,5-dihydro-1
H-imidazol-2-yl)-1-thiophene-2-ylethyl]pyridine (
4a) and the (+) isomer of 2-[2-(4,5-dihydro-1
H-imidazol-2-yl)-1-thiophene-3-ylethyl]pyridine (
4d) were found to give a significant increase in insulin release—in contrast to findings for their enantiomers—without influence on the K
ATP-channel. The (+) isomer (
4a) showed glucose dependent insulin release from β-cells at concentrations above 2.5 mM and a marked glucose lowering effect in
ob/
ob mice as well as in fed but not in fasted rats.</description><identifier>ISSN: 0223-5234</identifier><identifier>EISSN: 1768-3254</identifier><identifier>DOI: 10.1016/S0223-5234(03)00041-2</identifier><identifier>PMID: 12750022</identifier><identifier>CODEN: EJMCA5</identifier><language>eng</language><publisher>Oxford: Elsevier Masson SAS</publisher><subject>Animals ; Biological and medical sciences ; Dose-Response Relationship, Drug ; General and cellular metabolism. Vitamins ; Glucose - pharmacology ; Glucose dependent insulin release ; Hypoglycemic Agents - pharmacology ; Imidazoles - chemical synthesis ; Imidazoles - chemistry ; Imidazoles - pharmacology ; Imidazolines ; Insulin - metabolism ; Insulin Secretion ; Islets of Langerhans - drug effects ; Islets of Langerhans - metabolism ; K ATP current ; Medical sciences ; Mice ; Mice, Inbred Strains ; Models, Chemical ; Pharmacology. Drug treatments ; Potassium Channels - drug effects ; Potassium Channels - physiology ; Rats ; Stereoisomerism</subject><ispartof>European journal of medicinal chemistry, 2003-04, Vol.38 (4), p.357-362</ispartof><rights>2003 Éditions scientifiques et médicales Elsevier SAS</rights><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c443t-ce64d9b143325bccb327cc9e8d1b29661436bed1955b6b7b8025d77a8af125343</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0223-5234(03)00041-2$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>309,310,314,780,784,789,790,3550,23930,23931,25140,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14797989$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12750022$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jakobsen, Palle</creatorcontrib><creatorcontrib>Madsen, Peter</creatorcontrib><creatorcontrib>Andersen, HenrikSune</creatorcontrib><title>Imidazolines as efficacious glucose-dependent stimulators of insulin secretion</title><title>European journal of medicinal chemistry</title><addtitle>Eur J Med Chem</addtitle><description>Synthesis of a series of imidazolines with glucose dependent effects on insulin exocytosis from pancreatic β-cells is reported. Regioisomers and enantiomers were found to exhibit marked differences in exocytotic effects as well as different activities on the K
ATP-channel; the (
R (+)) isomer of 2-[2-(4,5-dihydro-1
H-imidazol-2-yl)-1-thiophene-2-ylethyl]pyridine (
4a) and the (+) isomer of 2-[2-(4,5-dihydro-1
H-imidazol-2-yl)-1-thiophene-3-ylethyl]pyridine (
4d) were found to give a significant increase in insulin release—in contrast to findings for their enantiomers—without influence on the K
ATP-channel. The (+) isomer (
4a) showed glucose dependent insulin release from β-cells at concentrations above 2.5 mM and a marked glucose lowering effect in
ob/
ob mice as well as in fed but not in fasted rats.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Dose-Response Relationship, Drug</subject><subject>General and cellular metabolism. Vitamins</subject><subject>Glucose - pharmacology</subject><subject>Glucose dependent insulin release</subject><subject>Hypoglycemic Agents - pharmacology</subject><subject>Imidazoles - chemical synthesis</subject><subject>Imidazoles - chemistry</subject><subject>Imidazoles - pharmacology</subject><subject>Imidazolines</subject><subject>Insulin - metabolism</subject><subject>Insulin Secretion</subject><subject>Islets of Langerhans - drug effects</subject><subject>Islets of Langerhans - metabolism</subject><subject>K ATP current</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred Strains</subject><subject>Models, Chemical</subject><subject>Pharmacology. Drug treatments</subject><subject>Potassium Channels - drug effects</subject><subject>Potassium Channels - physiology</subject><subject>Rats</subject><subject>Stereoisomerism</subject><issn>0223-5234</issn><issn>1768-3254</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1v1DAQhi0EotvCTwDlAiqHgD_j5FShio9KFRyAs2WPJ8goiRdPggS_Hm93RY-c5jDPO_PqYeyZ4K8FF92bL1xK1Rqp9CVXrzjnWrTyAdsJ2_WtkkY_ZLt_yBk7J_pRIdNx_pidCWkNr9sd-3Qzp-j_5CktSI2nBscxgYeUN2q-TxtkwjbiHpeIy9rQmuZt8msu1OSxSQttNdkQQsE15eUJezT6ifDpaV6wb-_ffb3-2N5-_nBz_fa2Ba3V2gJ2Og5BaFWbBoCgpAUYsI8iyKHr6qILGMVgTOiCDT2XJlrrez8KaZRWF-zl8e6-5J8b0urmRIDT5BeszZ1ViivBD6A5glAyUcHR7UuaffntBHcHke5OpDtYcly5O5FO1tzz04MtzBjvUydzFXhxAjyBn8biF0h0z2k72KEfKnd15LDq-JWwOIKEC2BMBWF1Maf_VPkL5beP0A</recordid><startdate>20030401</startdate><enddate>20030401</enddate><creator>Jakobsen, Palle</creator><creator>Madsen, Peter</creator><creator>Andersen, HenrikSune</creator><general>Elsevier Masson SAS</general><general>Elsevier</general><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>20030401</creationdate><title>Imidazolines as efficacious glucose-dependent stimulators of insulin secretion</title><author>Jakobsen, Palle ; Madsen, Peter ; Andersen, HenrikSune</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c443t-ce64d9b143325bccb327cc9e8d1b29661436bed1955b6b7b8025d77a8af125343</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Dose-Response Relationship, Drug</topic><topic>General and cellular metabolism. Vitamins</topic><topic>Glucose - pharmacology</topic><topic>Glucose dependent insulin release</topic><topic>Hypoglycemic Agents - pharmacology</topic><topic>Imidazoles - chemical synthesis</topic><topic>Imidazoles - chemistry</topic><topic>Imidazoles - pharmacology</topic><topic>Imidazolines</topic><topic>Insulin - metabolism</topic><topic>Insulin Secretion</topic><topic>Islets of Langerhans - drug effects</topic><topic>Islets of Langerhans - metabolism</topic><topic>K ATP current</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred Strains</topic><topic>Models, Chemical</topic><topic>Pharmacology. Drug treatments</topic><topic>Potassium Channels - drug effects</topic><topic>Potassium Channels - physiology</topic><topic>Rats</topic><topic>Stereoisomerism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jakobsen, Palle</creatorcontrib><creatorcontrib>Madsen, Peter</creatorcontrib><creatorcontrib>Andersen, HenrikSune</creatorcontrib><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>European journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jakobsen, Palle</au><au>Madsen, Peter</au><au>Andersen, HenrikSune</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Imidazolines as efficacious glucose-dependent stimulators of insulin secretion</atitle><jtitle>European journal of medicinal chemistry</jtitle><addtitle>Eur J Med Chem</addtitle><date>2003-04-01</date><risdate>2003</risdate><volume>38</volume><issue>4</issue><spage>357</spage><epage>362</epage><pages>357-362</pages><issn>0223-5234</issn><eissn>1768-3254</eissn><coden>EJMCA5</coden><abstract>Synthesis of a series of imidazolines with glucose dependent effects on insulin exocytosis from pancreatic β-cells is reported. Regioisomers and enantiomers were found to exhibit marked differences in exocytotic effects as well as different activities on the K
ATP-channel; the (
R (+)) isomer of 2-[2-(4,5-dihydro-1
H-imidazol-2-yl)-1-thiophene-2-ylethyl]pyridine (
4a) and the (+) isomer of 2-[2-(4,5-dihydro-1
H-imidazol-2-yl)-1-thiophene-3-ylethyl]pyridine (
4d) were found to give a significant increase in insulin release—in contrast to findings for their enantiomers—without influence on the K
ATP-channel. The (+) isomer (
4a) showed glucose dependent insulin release from β-cells at concentrations above 2.5 mM and a marked glucose lowering effect in
ob/
ob mice as well as in fed but not in fasted rats.</abstract><cop>Oxford</cop><pub>Elsevier Masson SAS</pub><pmid>12750022</pmid><doi>10.1016/S0223-5234(03)00041-2</doi><tpages>6</tpages></addata></record> |
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| ispartof | European journal of medicinal chemistry, 2003-04, Vol.38 (4), p.357-362 |
| issn | 0223-5234 1768-3254 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Animals Biological and medical sciences Dose-Response Relationship, Drug General and cellular metabolism. Vitamins Glucose - pharmacology Glucose dependent insulin release Hypoglycemic Agents - pharmacology Imidazoles - chemical synthesis Imidazoles - chemistry Imidazoles - pharmacology Imidazolines Insulin - metabolism Insulin Secretion Islets of Langerhans - drug effects Islets of Langerhans - metabolism K ATP current Medical sciences Mice Mice, Inbred Strains Models, Chemical Pharmacology. Drug treatments Potassium Channels - drug effects Potassium Channels - physiology Rats Stereoisomerism |
| title | Imidazolines as efficacious glucose-dependent stimulators of insulin secretion |
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