Discovery of cyclopentane- and cyclohexane- trans-1,3-diamines as potent melanin-concentrating hormone receptor 1 antagonists
The optimization of a HTS-derived lead compound into a potent and metabolically stable MCH-R1 antagonist is presented. We herein report the optimization of cyclopentane- and cyclohexane-1,3-diamine derivatives as novel and potent MCH-R1 antagonists. Structural modifications of the 2-amino-quinoline...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2007-08, Vol.17 (15), p.4232-4241 |
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| container_title | Bioorganic & medicinal chemistry letters |
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| creator | Giordanetto, Fabrizio Karlsson, Olle Lindberg, Jan Larsson, Lars-Olof Linusson, Anna Evertsson, Emma Morgan, David G.A. Inghardt, Tord |
| description | The optimization of a HTS-derived lead compound into a potent and metabolically stable MCH-R1 antagonist is presented.
We herein report the optimization of cyclopentane- and cyclohexane-1,3-diamine derivatives as novel and potent MCH-R1 antagonists. Structural modifications of the 2-amino-quinoline and thiophene moieties found in the initial lead compound served to improve its metabolic stability profile and MCH-R1 affinity, and revealed unprecedented SAR when compared to other 2-amino-quinoline-containing MCH-R1 antagonists. |
| doi_str_mv | 10.1016/j.bmcl.2007.05.034 |
| format | Article |
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We herein report the optimization of cyclopentane- and cyclohexane-1,3-diamine derivatives as novel and potent MCH-R1 antagonists. Structural modifications of the 2-amino-quinoline and thiophene moieties found in the initial lead compound served to improve its metabolic stability profile and MCH-R1 affinity, and revealed unprecedented SAR when compared to other 2-amino-quinoline-containing MCH-R1 antagonists.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2007.05.034</identifier><identifier>PMID: 17532215</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Biological and medical sciences ; Cyclohexanes - chemistry ; Cyclopentanes - chemistry ; Diamines - chemistry ; Diamines - pharmacology ; General and cellular metabolism. Vitamins ; Hormones. Endocrine system ; Humans ; MCH ; MCH-R1 antagonists ; Medical sciences ; Melanin-concentrating hormone receptor ; Models, Molecular ; Obesity ; Pharmacology. Drug treatments ; Receptors, Somatostatin - antagonists & inhibitors</subject><ispartof>Bioorganic & medicinal chemistry letters, 2007-08, Vol.17 (15), p.4232-4241</ispartof><rights>2007 Elsevier Ltd</rights><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c415t-75b3d7ffe1a0a90fb36667e620acd2107c24f44939ed41811bc886a4727e6f723</citedby><cites>FETCH-LOGICAL-c415t-75b3d7ffe1a0a90fb36667e620acd2107c24f44939ed41811bc886a4727e6f723</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0960894X07005872$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18909078$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17532215$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Giordanetto, Fabrizio</creatorcontrib><creatorcontrib>Karlsson, Olle</creatorcontrib><creatorcontrib>Lindberg, Jan</creatorcontrib><creatorcontrib>Larsson, Lars-Olof</creatorcontrib><creatorcontrib>Linusson, Anna</creatorcontrib><creatorcontrib>Evertsson, Emma</creatorcontrib><creatorcontrib>Morgan, David G.A.</creatorcontrib><creatorcontrib>Inghardt, Tord</creatorcontrib><title>Discovery of cyclopentane- and cyclohexane- trans-1,3-diamines as potent melanin-concentrating hormone receptor 1 antagonists</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>The optimization of a HTS-derived lead compound into a potent and metabolically stable MCH-R1 antagonist is presented.
We herein report the optimization of cyclopentane- and cyclohexane-1,3-diamine derivatives as novel and potent MCH-R1 antagonists. Structural modifications of the 2-amino-quinoline and thiophene moieties found in the initial lead compound served to improve its metabolic stability profile and MCH-R1 affinity, and revealed unprecedented SAR when compared to other 2-amino-quinoline-containing MCH-R1 antagonists.</description><subject>Biological and medical sciences</subject><subject>Cyclohexanes - chemistry</subject><subject>Cyclopentanes - chemistry</subject><subject>Diamines - chemistry</subject><subject>Diamines - pharmacology</subject><subject>General and cellular metabolism. Vitamins</subject><subject>Hormones. Endocrine system</subject><subject>Humans</subject><subject>MCH</subject><subject>MCH-R1 antagonists</subject><subject>Medical sciences</subject><subject>Melanin-concentrating hormone receptor</subject><subject>Models, Molecular</subject><subject>Obesity</subject><subject>Pharmacology. Drug treatments</subject><subject>Receptors, Somatostatin - antagonists & inhibitors</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1u1DAUhS0EokPhBVigbGCF0-vYjhOJDSq_UqVuisTOcpyb1qPEDranYha8ez3MSN3ByvLVd46vzyHkNYOaAWsvtvWw2LluAFQNsgYunpANE62gXIB8SjbQt0C7Xvw8Iy9S2gIwAUI8J2dMSd40TG7In08u2XCPcV-FqbJ7O4cVfTYeaWX8eJzc4e-_gxyNT5S953R0ZnEeU2VStYZcFNWCs_HOUxu8LfdosvO31V2IS_BYRbS45hArVmyzuQ3epZxekmeTmRO-Op3n5MeXzzeX3-jV9dfvlx-vqBVMZqrkwEc1TcgMmB6mgbdtq7BtwNixYaBsIyYhet7jKFjH2GC7rjVCNQWaVMPPybuj7xrDrx2mrJfybZzLxhh2SStQwKXg_wVZL5lUfVfA5gjaGFKKOOk1usXEvWagD-3orT60ow_taJC6tFNEb07uu2HB8VFyqqMAb0-ASdbMU8nbuvTIdT30oA6vfzhyWEK7dxh1sg5L7qMrQWc9BvevPR4AtMOu2A</recordid><startdate>20070801</startdate><enddate>20070801</enddate><creator>Giordanetto, Fabrizio</creator><creator>Karlsson, Olle</creator><creator>Lindberg, Jan</creator><creator>Larsson, Lars-Olof</creator><creator>Linusson, Anna</creator><creator>Evertsson, Emma</creator><creator>Morgan, David G.A.</creator><creator>Inghardt, Tord</creator><general>Elsevier Ltd</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>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20070801</creationdate><title>Discovery of cyclopentane- and cyclohexane- trans-1,3-diamines as potent melanin-concentrating hormone receptor 1 antagonists</title><author>Giordanetto, Fabrizio ; Karlsson, Olle ; Lindberg, Jan ; Larsson, Lars-Olof ; Linusson, Anna ; Evertsson, Emma ; Morgan, David G.A. ; Inghardt, Tord</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c415t-75b3d7ffe1a0a90fb36667e620acd2107c24f44939ed41811bc886a4727e6f723</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Biological and medical sciences</topic><topic>Cyclohexanes - chemistry</topic><topic>Cyclopentanes - chemistry</topic><topic>Diamines - chemistry</topic><topic>Diamines - pharmacology</topic><topic>General and cellular metabolism. Vitamins</topic><topic>Hormones. Endocrine system</topic><topic>Humans</topic><topic>MCH</topic><topic>MCH-R1 antagonists</topic><topic>Medical sciences</topic><topic>Melanin-concentrating hormone receptor</topic><topic>Models, Molecular</topic><topic>Obesity</topic><topic>Pharmacology. Drug treatments</topic><topic>Receptors, Somatostatin - antagonists & inhibitors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Giordanetto, Fabrizio</creatorcontrib><creatorcontrib>Karlsson, Olle</creatorcontrib><creatorcontrib>Lindberg, Jan</creatorcontrib><creatorcontrib>Larsson, Lars-Olof</creatorcontrib><creatorcontrib>Linusson, Anna</creatorcontrib><creatorcontrib>Evertsson, Emma</creatorcontrib><creatorcontrib>Morgan, David G.A.</creatorcontrib><creatorcontrib>Inghardt, Tord</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>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Giordanetto, Fabrizio</au><au>Karlsson, Olle</au><au>Lindberg, Jan</au><au>Larsson, Lars-Olof</au><au>Linusson, Anna</au><au>Evertsson, Emma</au><au>Morgan, David G.A.</au><au>Inghardt, Tord</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Discovery of cyclopentane- and cyclohexane- trans-1,3-diamines as potent melanin-concentrating hormone receptor 1 antagonists</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2007-08-01</date><risdate>2007</risdate><volume>17</volume><issue>15</issue><spage>4232</spage><epage>4241</epage><pages>4232-4241</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>The optimization of a HTS-derived lead compound into a potent and metabolically stable MCH-R1 antagonist is presented.
We herein report the optimization of cyclopentane- and cyclohexane-1,3-diamine derivatives as novel and potent MCH-R1 antagonists. Structural modifications of the 2-amino-quinoline and thiophene moieties found in the initial lead compound served to improve its metabolic stability profile and MCH-R1 affinity, and revealed unprecedented SAR when compared to other 2-amino-quinoline-containing MCH-R1 antagonists.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>17532215</pmid><doi>10.1016/j.bmcl.2007.05.034</doi><tpages>10</tpages></addata></record> |
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| ispartof | Bioorganic & medicinal chemistry letters, 2007-08, Vol.17 (15), p.4232-4241 |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Biological and medical sciences Cyclohexanes - chemistry Cyclopentanes - chemistry Diamines - chemistry Diamines - pharmacology General and cellular metabolism. Vitamins Hormones. Endocrine system Humans MCH MCH-R1 antagonists Medical sciences Melanin-concentrating hormone receptor Models, Molecular Obesity Pharmacology. Drug treatments Receptors, Somatostatin - antagonists & inhibitors |
| title | Discovery of cyclopentane- and cyclohexane- trans-1,3-diamines as potent melanin-concentrating hormone receptor 1 antagonists |
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