Conformational Analysis of the Anti-obesity Drug Lorcaserin in Water: How To Take Advantage of Long-Range Residual Dipolar Couplings
The conformational state of 8‐chloro‐1‐methyl‐2,3,4,5‐tetrahydro‐1H‐3‐benzazepine hydrochloride (lorcaserin) in water has been determined on the basis of one‐bond and long‐range CH residual dipolar coupling (RDC) data along with DFT computations and 3JHH coupling‐constant analysis. According to thi...
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| Veröffentlicht in: | Chemistry : a European journal 2013-10, Vol.19 (44), p.14989-14997 |
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| creator | Trigo-Mouriño, Pablo de la Fuente, M. Carmen Gil, Roberto R. Sánchez-Pedregal, Víctor M. Navarro-Vázquez, Armando |
| description | The conformational state of 8‐chloro‐1‐methyl‐2,3,4,5‐tetrahydro‐1H‐3‐benzazepine hydrochloride (lorcaserin) in water has been determined on the basis of one‐bond and long‐range CH residual dipolar coupling (RDC) data along with DFT computations and 3JHH coupling‐constant analysis. According to this analysis, lorcaserin exists as a conformational equilibrium of two crown‐chair forms, of which the preferred conformation has the methyl group in an equatorial orientation.
NMR‐based conformational analysis of flexible small molecules in solution is improved by the incorporation of long‐range CH residual dipolar couplings (RDCs; 2DCH) to one‐bond RDCs (1DCH; see picture). Applying this to the anti‐obesity drug, lorcaserin, shows that it exists in solution as two crown‐chair forms in equilibrium. |
| doi_str_mv | 10.1002/chem.201202509 |
| format | Article |
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NMR‐based conformational analysis of flexible small molecules in solution is improved by the incorporation of long‐range CH residual dipolar couplings (RDCs; 2DCH) to one‐bond RDCs (1DCH; see picture). Applying this to the anti‐obesity drug, lorcaserin, shows that it exists in solution as two crown‐chair forms in equilibrium.</description><identifier>ISSN: 0947-6539</identifier><identifier>EISSN: 1521-3765</identifier><identifier>DOI: 10.1002/chem.201202509</identifier><identifier>PMID: 24105936</identifier><identifier>CODEN: CEUJED</identifier><language>eng</language><publisher>Weinheim: WILEY-VCH Verlag</publisher><subject>Anti-Obesity Agents - chemistry ; Anti-Obesity Agents - pharmacology ; anti-obesity drugs ; Benzazepines - chemistry ; Chemistry ; Computation ; conformation analysis ; Conformational analysis ; Couplings ; Drugs ; Hydrochlorides ; Hydrogen Bonding ; Mathematical models ; Molecular Conformation ; NMR spectroscopy ; Nuclear Magnetic Resonance, Biomolecular ; Obesity ; Orientation ; Pictures ; residual dipolar couplings ; Water - chemistry</subject><ispartof>Chemistry : a European journal, 2013-10, Vol.19 (44), p.14989-14997</ispartof><rights>Copyright © 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><rights>Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.</rights><rights>Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5149-c87233d2a5a848c5ab9015bc9aa38b162ba5c79ea0b02520b13ea8f6f18007e53</citedby><cites>FETCH-LOGICAL-c5149-c87233d2a5a848c5ab9015bc9aa38b162ba5c79ea0b02520b13ea8f6f18007e53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fchem.201202509$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fchem.201202509$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24105936$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Trigo-Mouriño, Pablo</creatorcontrib><creatorcontrib>de la Fuente, M. Carmen</creatorcontrib><creatorcontrib>Gil, Roberto R.</creatorcontrib><creatorcontrib>Sánchez-Pedregal, Víctor M.</creatorcontrib><creatorcontrib>Navarro-Vázquez, Armando</creatorcontrib><title>Conformational Analysis of the Anti-obesity Drug Lorcaserin in Water: How To Take Advantage of Long-Range Residual Dipolar Couplings</title><title>Chemistry : a European journal</title><addtitle>Chem. Eur. J</addtitle><description>The conformational state of 8‐chloro‐1‐methyl‐2,3,4,5‐tetrahydro‐1H‐3‐benzazepine hydrochloride (lorcaserin) in water has been determined on the basis of one‐bond and long‐range CH residual dipolar coupling (RDC) data along with DFT computations and 3JHH coupling‐constant analysis. According to this analysis, lorcaserin exists as a conformational equilibrium of two crown‐chair forms, of which the preferred conformation has the methyl group in an equatorial orientation.
NMR‐based conformational analysis of flexible small molecules in solution is improved by the incorporation of long‐range CH residual dipolar couplings (RDCs; 2DCH) to one‐bond RDCs (1DCH; see picture). Applying this to the anti‐obesity drug, lorcaserin, shows that it exists in solution as two crown‐chair forms in equilibrium.</description><subject>Anti-Obesity Agents - chemistry</subject><subject>Anti-Obesity Agents - pharmacology</subject><subject>anti-obesity drugs</subject><subject>Benzazepines - chemistry</subject><subject>Chemistry</subject><subject>Computation</subject><subject>conformation analysis</subject><subject>Conformational analysis</subject><subject>Couplings</subject><subject>Drugs</subject><subject>Hydrochlorides</subject><subject>Hydrogen Bonding</subject><subject>Mathematical models</subject><subject>Molecular Conformation</subject><subject>NMR spectroscopy</subject><subject>Nuclear Magnetic Resonance, Biomolecular</subject><subject>Obesity</subject><subject>Orientation</subject><subject>Pictures</subject><subject>residual dipolar couplings</subject><subject>Water - chemistry</subject><issn>0947-6539</issn><issn>1521-3765</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc9v0zAYhi0EYmVw5YgsceGS4p-JzW3KxgoqIHVBO1pfUqfzlsTFThi984fjqqNCXCZZtj7peR9L34vQa0rmlBD2vrmx_ZwRygiTRD9BMyoZzXiRy6doRrQoslxyfYJexHhLCNE558_RCROUSM3zGfpd-qH1oYfR-QE6fJauXXQR-xaPNzbNo8t8baMbd_g8TBu89KGBaIMbcDrXMNrwAS_8Pa48ruAuRdY_YRhhY_eOpR822QqGNK2SZD2lP87d1ncQcOmnbeeGTXyJnrXQRfvq4T1F3z9eVOUiW367_FSeLbNGUqGzRhWM8zUDCUqoRkKtCZV1owG4qmnOapBNoS2QOm2DkZpyC6rNW6oIKazkp-jdwbsN_sdk42h6FxvbdTBYP0VDi0IRoSjTj6OSCCGZ4nvr2__QWz-FtMdECcFonopSiZofqCb4GINtzTa4HsLOUGL2VZp9leZYZQq8edBOdW_XR_xvdwnQB-DedXb3iM6Ui4sv_8qzQ9bF0f46ZiHcmbzghTTXXy_NZ7qqrq6EMBX_A46PuNQ</recordid><startdate>20131025</startdate><enddate>20131025</enddate><creator>Trigo-Mouriño, Pablo</creator><creator>de la Fuente, M. Carmen</creator><creator>Gil, Roberto R.</creator><creator>Sánchez-Pedregal, Víctor M.</creator><creator>Navarro-Vázquez, Armando</creator><general>WILEY-VCH Verlag</general><general>WILEY‐VCH Verlag</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</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>7SR</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>20131025</creationdate><title>Conformational Analysis of the Anti-obesity Drug Lorcaserin in Water: How To Take Advantage of Long-Range Residual Dipolar Couplings</title><author>Trigo-Mouriño, Pablo ; de la Fuente, M. 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Carmen</creatorcontrib><creatorcontrib>Gil, Roberto R.</creatorcontrib><creatorcontrib>Sánchez-Pedregal, Víctor M.</creatorcontrib><creatorcontrib>Navarro-Vázquez, Armando</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Chemistry : a European journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Trigo-Mouriño, Pablo</au><au>de la Fuente, M. 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According to this analysis, lorcaserin exists as a conformational equilibrium of two crown‐chair forms, of which the preferred conformation has the methyl group in an equatorial orientation.
NMR‐based conformational analysis of flexible small molecules in solution is improved by the incorporation of long‐range CH residual dipolar couplings (RDCs; 2DCH) to one‐bond RDCs (1DCH; see picture). Applying this to the anti‐obesity drug, lorcaserin, shows that it exists in solution as two crown‐chair forms in equilibrium.</abstract><cop>Weinheim</cop><pub>WILEY-VCH Verlag</pub><pmid>24105936</pmid><doi>10.1002/chem.201202509</doi><tpages>9</tpages></addata></record> |
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| subjects | Anti-Obesity Agents - chemistry Anti-Obesity Agents - pharmacology anti-obesity drugs Benzazepines - chemistry Chemistry Computation conformation analysis Conformational analysis Couplings Drugs Hydrochlorides Hydrogen Bonding Mathematical models Molecular Conformation NMR spectroscopy Nuclear Magnetic Resonance, Biomolecular Obesity Orientation Pictures residual dipolar couplings Water - chemistry |
| title | Conformational Analysis of the Anti-obesity Drug Lorcaserin in Water: How To Take Advantage of Long-Range Residual Dipolar Couplings |
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